case study example breast cancer

Building a Continuum of Care: Case Studies in HER2-Positive Breast Cancer

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Sara A. Hurvitz, MD, FACP

Professor of Medicine Head, Division of Hematology and Oncology Senior Vice President, Clinical Research Division Department of Medicine, UW Medicine Fred Hutchinson Cancer Center Seattle, Washington, United States  

Joyce A. O’Shaughnessy, MD

Celebrating Women Chair in Breast Cancer Research Baylor University Medical Center Chair, Breast Cancer Committee Breast Cancer Research Program Texas Oncology Sarah Cannon Research Institute Dallas, Texas

Sara M. Tolaney, MD, MPH

Associate Professor of Medicine Harvard Medical School Chief, Division of Breast Oncology Dana-Farber Cancer Institute Boston, Massachusetts

Amy Furedy, RN, OCN

Medical Education Director, Medscape, LLC 

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Case report of long-term survival with metastatic triple-negative breast carcinoma

Treatment possibilities for metastatic disease.

Editor(s): NA.,

Lifespring Cancer Treatment Center, Seattle, WA.

∗Correspondence: Bryce Douglas La Course, Lifespring Cancer Treatment Center, 510A Rainier Avenue South, Seattle, WA (e-mail: [email protected] ).

Abbreviations: ALL = acute lymphoblastic leukemia, CA = cancer antigen, CT = computed tomography, DC = dendritic cell, ER = estrogen receptor, GM-CSF = granulocyte-macrophage-colony-stimulating factor, HER2 = human epidermal growth factor receptor 2, MTD = maximum tolerated dose, PET = positron emission tomography, PR = progesterone receptor, TNBC = triple-negative breast cancer, Tregs = regulatory T cells.

Written informed consent was obtained from the patient in the study for publication of this case report and any accompanying images.

The authors have no conflicts of interest to disclose.

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

Rationale: 

Breast cancer is the most common as well as one of the most devastating cancers among women in the United States. Prognosis is poor for patients with metastatic breast cancer, especially for patients with so-called “triple-negative” disease. The lack of effective therapies for metastatic triple-negative breast cancer outlines the need for novel and innovative treatment strategies.

Patient concerns: 

A 58-year-old underwent a mastectomy which revealed a recurrent triple-negative breast carcinoma. Afterward, she presented with a growing mass in her left axilla and chest wall. A computed tomography scan showed axillary and supraclavicular adenopathy, nodules in the left upper and lower lobe of the lungs, and 2 areas of disease in the liver. A bone scan showed lesions in the ribs.

Diagnosis: 

The patient was diagnosed with a recurrent metastatic triple-negative breast carcinoma that spread to the lung, liver, and bones.

Interventions: 

The patient was treated with metronomic chemotherapy, sequential chemotherapy regimens, and immunotherapy.

Outcomes: 

The patient is now over 15 years out from her diagnosis of metastatic disease without any evidence of recurrent disease, likely due to the patient's treatment strategy which included sequential metronomic chemotherapy regimens and immunotherapy.

Lessons: 

Sequential metronomic chemotherapy regimens in combination with immunotherapy might be an effective treatment option for patients with metastatic triple-negative breast cancer. We hope that this case can provide some guidance for the treatment of metastatic triple-negative breast cancer and motivate research that can potentially lead to more cases of long-term survival for patients who develop this dismal disease.

1 Introduction

Breast cancer remains the most common cancer diagnosed among women in the United States and is the second leading cause of cancer-related deaths, with approximately 41,000 patients projected to die from this disease in 2018 alone. [1] The prognosis for patients with metastatic breast cancer varies based on many factors including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. Tumors that do not express the ER, PR, or HER2 receptors are known as “triple-negative” breast cancers (TNBCs) and represent approximately 11% of all breast cancers. [2] This subtype of breast cancer is known for being aggressive, having a high probability of distant recurrence after adjuvant therapy, and progressing quickly on palliative chemotherapy treatment in the metastatic setting. [2,3] Patients with metastatic TNBC have a poor prognosis, with a median overall survival of 13.3 months with treatment. [3] Continuing chemotherapy treatment until disease progression is currently the standard of care for patients with metastatic TNBC, with no preferred chemotherapy regimens established at this time. The lack of effective therapies for this aggressive disease highlights the need for the development of novel treatment strategies. Here we report the case of a patient with metastatic TNBC that metastasized to the lungs, liver, and bones who achieved long-term remission without evidence of disease recurrence after 15 years. Her case is followed by a discussion of the treatment strategy which likely has led to her remarkable survival.

2 Case report

A Caucasian female initially presented with a nodule in her left breast in March 2001 at the age of 56. Before this, the patient was a homemaker with a relatively unremarkable past medical history aside from some mild arthritis. Her father and brother had prostate cancer, and her mother apparently had uterine cancer. Her social history was negative for tobacco, alcohol as well as illicit drug use. A core biopsy performed in mid-April 2001 showed a high-grade infiltrating ductal carcinoma, with a Bloom–Richardson score of 9/9. Immunohistochemistry showed that the tumor was positive for ER expression and negative for PR expression and HER2 overexpression. The patient underwent a left lumpectomy with an axillary lymph node dissection shortly after the biopsy. Pathology revealed a 2.0 × 1.8 × 1.3 cm high-grade invasive ductal carcinoma. 0 of the 15 left axillary lymph nodes examined were positive for carcinoma, and no lymphatic invasion was identified. The patient declined adjuvant chemotherapy and radiation therapy.

In the spring of 2003, the patient noticed another mass under the nipple of her left breast. An ultrasound-guided left breast biopsy was performed in early May 2003 which revealed a high-grade ductal carcinoma. The patient then underwent bilateral simple mastectomies to remove the left breast tumor in late May 2003. Pathology of the left breast mass showed a poorly-differentiated carcinoma that measured 3.0 × 3.5 × 2.0 cm with a Bloom–Richardson score of 9/9. The tumor was negative for ER, PR, HER2 by immunohistochemistry, and for amplification of the HER2 gene by fluorescence in situ hybridization, indicating she had triple-negative recurrent disease ( Fig. 1 ). The patient again declined any treatment.

In early September 2003, the patient noticed a growing mass in her left axilla and chest wall. A computed tomography (CT) scan of the chest showed a 3.8 cm necrotic left axillary lymph node with axillary and supraclavicular adenopathy. Nodules were also seen in the left upper and lower lobe of the lungs along with 2 subtle areas of low attenuation in the liver. A bone scan performed in December 2003 revealed bone lesions along the left 3rd and 6th ribs posterolaterally. The patient was concluded to have metastatic disease to the lungs, liver, and bones. Unfortunately, these images have been destroyed by the imaging facility and cannot be used in this publication. The details of the scans were obtained from the official written scan reports.

After consulting with the patient, she decided to proceed with chemotherapy treatment. She was given 4 sequential chemotherapy regimens ( Table 1 ) to try and control her cancer along with monthly zoledronic acid to try to prevent bone complications due to her osseous metastases. Granulocyte-macrophage-colony-stimulating factor (GM-CSF) was used throughout the treatment to prevent or treat chemotherapy-induced neutropenia as well as stimulate the immune system. After 14 doses of weekly paclitaxel and carboplatin, there was remarkable tumor shrinkage in the left chest wall and axillary area on her physical examinations. Her cancer antigen (CA) 27.29 (normal range: <38 U/mL) also decreased from a pretreatment level of 52.1 to 19.8 in mid-April 2004 which was consistent with the patient's physical exam findings. The patient's CA 27.29 then remained within normal range from this point onward. The patient was then switched to weekly doxorubicin liposome in June 2004. Twelve doses were planned, but she only received 8 doses due to developing palmar-plantar erythrodysesthesia. Her symptoms resolved after the drug was withdrawn in late July 2004. The patient then continued chemotherapy treatment and received 6 doses of weekly gemcitabine and cisplatin from August 2004 to October 2004. The patient developed thrombocytopenia and her second to the last dose of this regimen was given with a reduced dose of cisplatin. Gemcitabine was dose reduced during her last infusion of this regimen. She was then switched to weekly vinorelbine in early December 2004 and completed 12 doses of chemotherapy treatment in late February 2005.

Aside from developing neutropenia and thrombocytopenia secondary to chemotherapy treatment and palmar-plantar erythrodysesthesia secondary to doxorubicin liposome, the patient tolerated her treatment relatively well. A CT scan performed in March 2005 showed no evidence of disease in the lung and liver. The patient was taken off of chemotherapy treatment but continued on monthly zoledronic acid and pursued a watchful waiting approach from February 2005 to June 2005.

In June 2005 the patient developed several small skin nodules in her left axillary chest wall. A positron emission tomography (PET) and CT scan performed shortly after showed minimal thickening of the left chest wall, suspicious for recurrent disease, although no biopsy was performed. There was no other evidence of metastatic disease. She was started on imiquimod cream, which was applied on the skin nodules, for immune stimulation. The patient reported pruritus and erythema in the applied area, but she did not complain of having any pain. These nodules resolved after a few weeks. In October 2005, the patient noticed several pea-sized nodules in her left axilla which were also suspicious for disease recurrence. The patient continued applying imiquimod cream to the area. She developed erythema, ulceration, and skin breakdown in that area, but this resolved after stopping imiquimod. The skin nodules resolved by January 2006. The patient's condition continued to improve, and the frequency of her zoledronic acid infusions was reduced to every other month in May 2006, and then quarterly in September 2007. In December 2008 she continued with biannual infusions of zoledronic acid. A germline BRCA1 and BRCA2 analysis performed in December 2009 did not detect any mutations. Routine PET/CT and CT scans continue to show no evidence of recurrent or persistent metastatic disease. The patient is now 73 years old and is enjoying a good quality of life. She is currently over 15 years out from her diagnosis of recurrent metastatic TNBC.

3 Discussion

The prognosis of this patient before starting treatment was particularly poor, not only because her tumor did not express the ER, PR, or HER2 receptors, but also because she had stage IV disease with multiple visceral metastases. With the typical prognosis of metastatic TNBC being slightly over 1 year, the 15-year survival of this patient is quite remarkable, especially given that she is currently free of disease and has not received any chemotherapy treatment since late February 2005. To our knowledge, this patient is the longest reported survivor of metastatic TNBC. Her long-term survival without recurrence suggests that this patient may be cured of a cancer that is not thought to be curable. We believe that our treatment methodology, which included using metronomic chemotherapy, switching chemotherapy regimens before anticipated disease progression, and utilizing immune therapies, all contributed to her outstanding survival. Below, we will describe each of these treatment strategies in detail.

3.1 Metronomic chemotherapy

The dosing of a standard chemotherapy regimen is based on a maximum tolerated dose (MTD). This dose is typically the highest possible dose that is not lethal to the patient. The idea of an MTD was originally developed with the logic that “more is better” to try and maximize the amount of cancer cell death. A high dose of chemotherapy can kill cancer cells, but due to the relatively nonspecific mechanism of action of most chemotherapy agents, this high dose of chemotherapy can also result in clinical toxicities which is why standard chemotherapy regimens are often administered every 3 weeks. The breaks in between standard chemotherapy doses are crucial for the recovery of normal tissues, but logically this can also give time for cancer cells to grow and progress as well. Thus, the dosing of chemotherapy agents and the frequency of chemotherapy administration may play an important role in the efficacy of treatment as well as the patient's quality of life.

This patient received lower doses of chemotherapy on a more frequent basis, also known as “metronomic chemotherapy.” Although lower doses of chemotherapy agents were given to this patient during each administration, the overall dose intensity (the total dose of chemotherapy administered per unit time) of her chemotherapy agents was a similar, if not higher, dose intensity, compared to the standard dosing of each respective chemotherapy agent. Studies have shown that reducing dose intensity, most commonly due to myelosuppression, correlates with poorer disease-free survival and overall survival, while maintaining a relatively high planned dose intensity is associated with better clinical outcomes. [4] Due to the lower doses used during each administration, metronomic chemotherapy regimens can minimize severe adverse events and prolonged drug-free breaks. In addition, a more steady dosing schedule may actually kill more cancer cells by maintaining a more constant drug concentration in the body. This logic may explain why dose-dense regimens (chemotherapy regimens with an increased frequency of administration) have been shown to be more effective in the treatment of several kinds of cancer, including breast cancer, when compared to standard treatment. [5] We have also treated pancreatic cancer patients using a similar dosing strategy, which has yielded exciting results. [6,7]

The main mechanism of action of metronomic chemotherapy was initially thought to be its effects on endothelial cells resulting in antiangiogenic effects. There is a fair amount of literature that suggests that paclitaxel has antiangiogenic effects when administered in lower doses more frequently. [8] Likely due to their aggressive nature, TNBCs are known to have enhanced angiogenesis. [9] The proangiogenic tumor microenvironment creates an abnormal vascular network that can result in increased interstitial pressure and decrease drug penetration, ultimately decreasing the efficacy of systemic treatment. [10] By blocking angiogenesis and normalizing the tumor vasculature, more chemotherapy can reach the tumor, potentially improving the efficacy of treatment.

In addition to having direct cytotoxic and antiangiogenic effects, it has been discovered that metronomic chemotherapy can also have antistromal and immunostimulatory effects. [11–13] There are even some thoughts that the effects that metronomic chemotherapy has on the tumor microenvironment can decrease the rate of acquired chemotherapy resistance. [11,12] Targeting both cancer cells and the tumor microenvironment may play an important role in the future of cancer treatment.

3.2 Sequential chemotherapy regimens

The standard way to administer chemotherapy treatment is to continue a single chemotherapy regimen until noticeable disease progression. Patients with metastatic TNBC tend to relapse quickly on chemotherapy treatment, likely due to acquired disease resistance. [3] Drug resistance is seen as the primary cause of failure of chemotherapy treatment for cancer and continuing a chemotherapy regimen until disease progression will inevitably breed chemotherapy-resistant disease. Switching chemotherapy regimens before disease progression, as we did for this patient, may prevent the development of disease resistance, allowing for a continual decrease in the number of cancer cells, and perhaps a better chance of achieving long-term survival.

Tumors are known to have a large amount of genetic diversity, even within a single mass, and chemotherapy treatment can induce strong selective pressure for cells that have intrinsic or acquired mutations which can resist treatment. [14] Switching chemotherapy agents may eradicate cancer cells that developed resistance to the cytotoxic agents in the previous regimen, especially if the new chemotherapy agents have a different mechanism of action. There are even some suggestions that cancer cells can become dependent on certain therapies after long-term drug exposure, and switching the drugs used may increase treatment efficacy by inducing cell death of the cancer cells that have become “addicted” to the previous therapy. [12,13] The idea of switching chemotherapy treatments before the development of disease resistance has broad implications and could transform the idea of cancer being an acute disease to more of a chronic illness. In addition to potentially increasing treatment efficacy and preventing the development of disease resistance, switching treatment regimens can also help prevent the accumulation of chemotoxicity from a single chemotherapy regimen, which can improve the quality of life of patients receiving treatment.

This idea of sequential chemotherapy regimens has been successfully introduced in the treatment of metastatic non-small cell lung carcinoma. Patients who responded to first-line chemotherapy and pursued a switch maintenance therapy were found to have improved overall survival compared to placebo or observation, and switch maintenance therapy was also less toxic compared to continuous maintenance therapy. [15] A similar treatment strategy has also been applied and has found major success in the treatment of pediatric acute lymphoblastic leukemia (ALL). A diagnosis of ALL was fatal for children in the 1950s. Currently, this disease has a cure rate of more than 80% in children. The current treatment for ALL involves several combination chemotherapy regimens that are given sequentially to eliminate any remaining disease. [16] Sequential chemotherapy regimens in ALL has been considered one of the greatest achievements in the field of oncology to date.

This patient received several different chemotherapy regimens sequentially ( Table 1 ). Her first regimen consisted of paclitaxel and carboplatin. Paclitaxel that is administered on a weekly basis has been shown to be superior to paclitaxel that is administered every 3 weeks in the treatment of metastatic breast cancer, with increased response rates, time to progression, as well as survival. [17] Moreover, there is some evidence that platinum-based chemotherapy regimens improve the overall survival of patients with metastatic TNBC. [18] The addition of platinum agents to treatment regimens has likely been slow to catch on due to the significant toxicity of the standard doses of these agents. However, the carboplatin dose of AUC 2.25 and cisplatin dose of 15 to 20 mg/m 2 that was given on a weekly basis were tolerated relatively well by this patient.

After she received 14 doses of paclitaxel and carboplatin, she was switched to weekly doxorubicin liposome. Anthracyclines are known to be very effective in the treatment of breast cancer, but carry a risk of cardiotoxicity and significant myelosuppression. We prefer to use doxorubicin liposome instead of doxorubicin because doxorubicin liposome has a favorable toxicity profile, less hematological toxicity, and has been found to cause less cardiotoxicity compared to doxorubicin. [19] This is an important consideration to reduce potential comorbidities in the future, especially if patients have the potential to achieve long-term survival. The patient tolerated treatment with weekly doxorubicin liposome well aside from developing palmar-plantar erythrodysesthesia, but perhaps this treatment might be more tolerable if it was administered every 2 weeks due to doxorubicin liposome's relatively long half-life. This treatment might also be more effective if it was combined with weekly paclitaxel.

The patient's next regimen, gemcitabine, and cisplatin, has been shown to improve outcomes in patients with metastatic TNBC compared to patients without metastatic TNBC. [20] The patient also tolerated this regimen well aside from developing thrombocytopenia, but maybe this could be lessened by starting with a dose of gemcitabine 600 mg/m 2 and cisplatin 15 mg/m 2 instead of gemcitabine 750 mg/m 2 and cisplatin 20 mg/m 2 , which is what we have done subsequently with other patients. Her final regimen consisted of vinorelbine, which is another effective drug for the treatment of metastatic breast cancer patients who have been exposed to anthracyclines and taxanes in previous treatments. [21] Since the patient's diagnosis 15 years ago, there are several new treatments available that may be more effective than vinorelbine, such as eribulin or irinotecan.

By giving this series of effective treatments sequentially, we believe that this prevented disease resistance and allowed the patient to achieve complete remission after approximately 1 year of treatment. The combination of agents was chosen to avoid overly additive side effects, such as myelosuppression, so that the patient could receive continuous treatment without interruption and also maintain a relatively high overall dose intensity. In regards to the order of these regimens, it is unknown whether or not this is the most optimum sequence of regimens and this should be further investigated.

3.3 Immunotherapy

More evidence is accumulating suggesting that some subtypes of metastatic TNBC can be particularly responsive to immunotherapy, with some studies showing promising results. [22] However, cancers can escape an antitumor immune response in several ways such through the upregulation of regulatory T cells (Tregs) and secretion of immunosuppressive cytokines into the tumor microenvironment as well as through the expression of immunosuppressive proteins, such as programmed death-ligand 1, on the cell surface. [22–24] The situation is further exacerbated by the immunosuppressive effect of standard dose chemotherapy. [25] When the immunosuppressive activity of the tumor outweighs the body's antitumor immune response, this is thought to promote tumor progression.

Metronomic chemotherapy, in addition to having a lesser impact on blood counts, is thought to have immunomodulatory properties. In preclinical studies, low-dose paclitaxel and gemcitabine have been shown to decrease the number and viability of Tregs as well as myeloid-derived suppressor cells in the tumor microenvironment, which could potentially allow for a more potent antitumor immune response. [26] Moreover, the antiangiogenic effects of metronomic chemotherapy may be synergistic with its immunostimulatory properties. Normalizing the tumor vasculature could allow the immune system to better reach the tumor bed, just as it is thought to allow more chemotherapy treatment to reach the tumor. Interestingly, the patient also received zoledronic acid due to her bone metastases, which may also have immunomodulatory properties. This effect seems to be more prevalent in ER-positive breast cancer cells, but more research will need to be conducted to assess the immunomodulatory properties in ER-negative breast cancer. [27]

The patient also received several immunostimulatory agents which may have played a role in her long disease-free remission. While receiving chemotherapy treatment, the patient received GM-CSF to prevent or treat chemotherapy-induced neutropenia. We prefer the use of GM-CSF compared to other colony-stimulating factors because GM-CSF stimulates both the granulocyte as well as the monocyte/macrophage and dendritic cell (DC) lines, while other colony-stimulating factors only stimulate the granulocyte cell line. DCs are crucial for antigen presentation and activation of the adaptive immune system and macrophages can remove dead tumor cells via phagocytosis. Moreover, preclinical evidence suggests that low-dose paclitaxel can stimulate DC maturation and the anthracyclines can promote the phagocytosis of tumor cells by DCs, suggesting a synergistic role of GM-CSF in combination with 2 of the patient's chemotherapy regimens. [28]

The patient also applied imiquimod topically to small superficial lesions in her left axillary region that were likely secondary to recurrent disease. Imiquimod has known antitumor activity in superficial basal cell carcinoma and it is thought to work by stimulating the innate and adaptive immune system in the applied area via toll-like receptor 7. [29] The patient's left axillary lesions resolved after she applied imiquimod cream to the area, suggesting that imiquimod may be able to be used to treat superficial metastases from TNBC. One small study also had similar findings, and it would be interesting to investigate whether metastatic TNBC was more responsive to local immunotherapy than other breast cancer types. [30] Perhaps the success of imiquimod in this patient was due to the minimal tumor burden the patient had at the time, especially considering that a smaller tumor size in basal cell carcinoma is correlated with a more favorable prognosis after treatment with imiquimod.

4 Conclusion

The patient described in this case report is now 15 years out from her diagnosis of recurrent metastatic TNBC without evidence of persistent or recurrent metastatic disease. Her treatment, which included the use of sequential metronomic chemotherapy regimens as well as several immunotherapies, was tolerated relatively well and likely contributed to her remarkable survival. Although this is only 1 case, we have treated another patient with metastatic TNBC with a similar strategy who is now over 6 years out and free of disease as well as a few other patients who achieved longer than average survivals. We are planning to publish this data in a small case series in the future. We hope that this encouraging case can offer hope to those who are suffering from this debilitating disease and spark the formation of larger clinical trials to further evaluate this treatment strategy due to the potential significant medical, psychological, and economic implications. These ideas not only have the possibility to shift the paradigm of treating metastatic TNBC, but also potentially other metastatic cancers as well.

Acknowledgments

We would like to thank Max Tse and Jeffrey Wang for drafting earlier versions of this paper, and Emmanuel De Dios, without whom none of this work could have been done.

Author contributions

Conceptualization: Ben Man-Fai Chue, Bryce Douglas La Course.

Formal analysis: Ben Man-Fai Chue, Bryce Douglas La Course.

Writing – original draft: Ben Man-Fai Chue, Bryce Douglas La Course.

Writing – review and editing: Ben Man-Fai Chue, Bryce Douglas La Course.

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Case Study: Breast cancer patient

‘Running a half marathon isn’t something you might expect of someone who’s just had breast cancer, but I was keen to get back to doing the things I love.’

Hepin* had been diagnosed with triple negative breast cancer late in 2014, before going on to have surgery. Her treatment was initially successful, and for a number of years she led an active lifestyle.

But in May 2018 she started to notice a change. ‘I was feeling more tired than usual – yawning and flagging easily,’ she explains.

After undergoing further tests, she received the news: the cancer had returned, this time spreading to lymph nodes in her armpit. She went through more treatment – this time having chemotherapy and radiotherapy. 

‘A few months later, we went for a scan and it wasn’t good news,’ she says. Doctors told her that images showed possible disease in other parts of her body.

‘Obviously this was devastating to hear,’ she says. ‘But we were keen to get another opinion, to make sure this was the case, and to check what my treatment plan should be.’

Hepin and her husband looked to international centres for expert advice, before choosing The Royal Marsden. ‘I’d heard it was one of the world leading institutions treating breast cancer.’ she explains. 

When she arrived at The Royal Marsden Hepin said she immediately noticed the calming atmosphere. ‘It was serene and quiet – it felt homely and not as busy as some of the hospitals we have at home.’ she explains.

After undergoing an MRI scan, her consultant Professor Stephen confirmed the good news; she wouldn’t need any further treatment for now, but should keep having regular checks to monitor her health.

‘Overall we were very pleased with our experience at The Royal Marsden,’ Hepin says. ‘They made us feel welcomed and comfortable and all the staff were so accommodating. The translation service provided was also of great help for us.’

*Not her real name

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It was serene and quiet – it felt homely and not as busy as some of the hospitals we have at home. Hepin, breast cancer patient

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Patient Case Presentation

Patient Mrs. B.C. is a 56 year old female who is presenting to her WHNP for her annual exam. She had to cancel her appointment two months ago and didn’t reschedule until now. Her last pap smear and mammogram were normal. Today, while performing her breast exam, her nurse practitioner notices dimpling in the left breast as the patient raises her arms over her head. When the NP mentions it to Mrs. B.C. she is surprised and denies noticing it before today. A firm, non-tender, immobile nodule is palpated in the upper quadrant of her breast . The NP then asks Mrs. B.C. how frequently she is performing breast self-exams, she admits to only doing them randomly when she remembers, which is about every few months. She reports no recent or abnormal drainage from her breast. Further examination reveals palpable axillary lymph nodes. 

Mrs. B.C. is about 30 pounds overweight and walks her dog around her neighborhood every morning before work and every evening when she gets home. She reports drinking a glass of white wine before bed each night. She denies any history of tobacco use. She reports use of a combination birth control pill on and off for 25 years until she reached menopause. She is not currently taking any prescription medications. 

Past Medical History

• Menarche (Age 10)
• Post-menopausal (Age 53)
• No other pertinent medical history

Family History:

• Father George- deceased from stroke (75 years old), history of hypertension, CAD, HLD
• Mother Maryanne alive- 76 years old, history of dementia, osteoporosis 
• Brother Michael- alive, 57 years old, history of hypertension, CAD and cardiac stent placement (54 years old)
• Sister, Michelle- alive 53 years old, history of GERD, Asthma
• Brother- Jimmy- alive 50 years old, no past medical history

Social History: 

Mrs. B.C. works Monday-Friday 8am-5pm at the local dentist’s office at the front desk as a schedule coordinator. She is planning to retire in a few years. In her spare time, she is involved in various community efforts to feed the homeless and helps to prepare dinners at her local church one night a week. She also enjoys cooking and baking at home, gardening, and nature photography. 

Mrs. B.C. has two children. Her oldest son, Patrick, is 21 years old and is in his final year of pre-med. He is attending a public university about 2 hours away from home where he lives year-round. As an infant, Patrick was breastfed until 18 months when he self-weaned. Her daughter, Veronica, is 19 years old and lives at home while attending the local branch campus of a state university. She is in her second year of a business degree and then plans to transfer to the main campus next year. When Veronica was an infant she had difficulty latching onto the breast due to an undiagnosed tongue and lip ties resulting in Mrs. BC exclusively pumping and bottle feeding for six months. After six months, Mrs. B.C. was having a hard time keeping up while working and her found her supply diminished. Veronica had begun eating solid foods so Mrs. B.C. switched to supplemental formula, which was a big relief.

Mrs. B.C. was married to her now ex-husband Kent for 26 years. They divorced two years ago when Veronica was a senior in high school. They have remained friends and Kent lives 25 minutes away in a condo with his girlfriend. She also has two brothers who live nearby and a sister who lives out of state. Her 7 nieces and nephews range in age from 9 years old to 26 years old. Her father, George, passed away from a sudden stroke 4 years ago. Her mother, Maryanne, has dementia and is living in a nearby memory care facility. She also has many close friends. 

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17 TROPION-Breast05: A Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Versus Chemotherapy (CT) Plus Pembrolizumab in Patients (pts) With PD-L1–Positive Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (TNBC)

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Neil M. Iyengar, MD, and Paolo Tarantino, MD, discuss updated data on agents such as T-DXd and abemaciclib in breast cancer presented at 2024 ASCO.

19 Efficacy, Safety, and Quality of Life With Ribociclib + Endocrine Therapy in Elderly Patients With HR+/HER2– Advanced Breast Cancer Across the MONALEESA-2, -3, and -7 Trials

Finding a Place for Exercise Oncology in the Treatment of Breast Cancer

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Breast Cancer Cryoablation May Be Safer Alternative to Invasive Surgery in Select Patients

Retrospective analysis found that cryoablation was associated with infrequent AEs and low recurrence rates among patients with breast cancer.

20 Final Overall Survival (OS) Analysis From the Phase 3 TROPiCS-02 Study of Sacituzumab Govitecan (SG) in Patients (pts) With Hormone Receptor–Positive/HER2-Negative (HR+/HER2–) Metastatic Breast Cancer (mBC)

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Pam's breast cancer story

Pam was diagnosed with breast cancer in 2021 at the age of 67. Pam shared her story with us in March 2021.

My Diagnosis

In March 2020 I noticed my left nipple was permanently inverted. I went to my GP as I knew this could be a warning sign of breast cancer. My doctor referred me to the local hospital for a 2 week One Stop Breast Service appointment. I attended on the 10th March. They reassured me it was probably caused by a collapsed milk duct. 

I then noticed discharge and crusting from the nipple. This happened several times during December 2020 and January 2021. I went back to my GP. I was referred again to the local hospital under the 2 week cancer check rules. I had a mammogram, chest x-ray, breast scan and biopsy. The following week I was asked to return for further biopsies. That’s when I knew something suspicious had been found.

Two weeks after I got the results. I was shocked to find it was cancer but felt confident that it had been found quite early. I met with the Breast Care Nurse as well as the surgeon and was given lots of reassurance and information to read. I was told I would need a mastectomy.

My treatment

I was anxious but was relieved to find out that I wouldn’t need any more treatment after the mastectomy. It was just yearly check ups and mammograms. I decided not to have a breast reconstruction. I felt that a mastectomy bra and breast sponge would be OK for me. 

I asked why I wasn’t having chemotherapy or any other medication. I wondered whether my age had anything to do with it. I was told it wasn’t due to my age. As it was a small growth that hadn’t spread anywhere else so nothing else was required just yearly check ups.

Coping after treatment

It has been an isolating experience due to the COVID 19 lockdown. No coffee mornings for me or visits to the Purley Cancer Centre for chats or sessions of aromatherapy or reflexology. I have been able to avail myself to some telephone counselling though which has been helpful. At night when I can’t sleep, I do go on the internet and do my research, some good, some bad. Being able to talk face to face is something I miss though. In normal circumstances I would be meeting up with friends, attending support groups and interacting with other people.

Information can be overwhelming sometimes and if you have no further appointments to attend at the hospital and cancer help centres are closed, life does feel devoid of personal interaction. Telephone help lines are great, but not quite the same as face to face contact.

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Journal of Hematology & Thromboembolic Diseases Open Access

ISSN: 2329-8790

Case Report - (2021)Volume 9, Issue 12

A Case Report of 58-Year-Old Female with Breast Cancer after Mastectomy of Left Breast and Axillary Lymph Node Dissection

Author info »

Breast cancer is Malignment cell growth in the breast. If the cancer isn't treated, it will spread to other parts of the body. Except for skin cancer, the most frequent type of cancer among women is breast cancer. Mammograms can detect breast cancer early, possibly before it has spread. Main symptoms and/or important clinical findings: A 58-year-old female patient registered to the surgery department on 05/10/2021 with the main complaint of pain in the left breast for 1 year and a lump in the left breast for 9 months. Now she came to AVBRH for further treatment of that. The main Diagnosis, therapeutic intervention, and outcomes: The doctor identified a case of cancer of the left breast after a physical examination and all investigations such as blood, FNAC, biopsy, Mammography Colour Doppler USG. For that Doctor advice the surgery and 22/10/2021 mastectomy of the left breast and axillary lymph node dissection was done. Dressing of suturing site. Inj Cefixime 1 Gm BD, Tab. Pan 40 Mg OD, Tab. Dolo 650 Mg Sos, Syp. Orofer Xt 2tsf Bd, Syp. Lupizyme 2tsf BD, Protein Powder 2 Spun TDS, Syp Duphalac 20 Ml Hs, Steam Inhalation TDS, Nebulization with Normal Saline TDS, Tab. Diclomol SP Bd, Tab. Limcee Od, Cap. Because Od, Spirometer for Breathing Exercise, Chest Physiotherapy, all the treatment was taken and the result was fine. Conclusion: She responded to both medicine and physician counseling.

Carcinoma in breast; Ductal carcinoma in Situ, Mammogram; Axillary lymph node dissection

Introduction

The most frequent type of cancer among women is breast cancer. [ 1 , 2 ] after skin cancer most frequent cancer among women is breast cancer. 66 % of breast cancer patients identified beyond the age of 55, becoming older is the commonest risk factor for developing this disease [ 3 ]. Cancers developing from the ducts that called ductal carcinomas. [ 4 , 5 ].

a breast cancer diagnosis is confirmed by taking a biopsy of the concerning tissue. Following the diagnosis, more tests are performed to see if cancer has spread beyond the breast and to identify which treatments are most likely to be effective. For prognostic and curative goals, axillary lymph node dissection is the therapy of choice in locally advanced breast cancer [ 6 ].

Breast cancer is the most frequent cancer in women around the world, accounting for over a quarter (23%) of all malignancies in women. In 2008, about 1.4 million women were diagnosed with breast cancer worldwide, with 459,000 deaths reported. The worldwide breast cancer burden is predicted to exceed 2 million by 2030, with rising proportions from developing countries [ 7 , 8 ]. In India, 145,000 women were diagnosed with breast cancer in 2012, with an age-standardized incidence rate of 25.8 per 100,000 women. In the year 2012, India's death toll was expected to be around 70,000.7 Breast cancer incidence rates in India vary by 3–4 times across the country, with the highest rates found in the Northeast and big metropolises like Mumbai and New Delhi [ 9 ].

Patient Information: A 58 years old female patient was admitted to the female surgery ward on 05/10/2021 with a complaint of pain in the left breast for 1 year and a lump in the left breast for 9 months after the history & physical examination and all investigation done and diagnosed the carcinoma of the left breast. For further treatment of that doctor advice the surgery and on 22/10/2021 left-sided mastectomy with axillary lymph node dissection surgery was done.

Past medical and surgical history, and relevant outcomes from interventions : 1 month before they visited the private hospital for the same complaint, after investigation report such as left breast FNAC and mammography showing breast cancer. Now she came to further treatment of that. Other than that, she was not having any history of DM, HTN, TB. Her Tubal ligation operation was done for 25 years. She was belonging to a nuclear family. Not having any significant history of this disease. All family members are healthy. She maintained a good interpersonal relationship with the family members except for her husband and not having any bad habits like tobacco chewing etc. The sleeping pattern was normal bowel and a bladder habit is normal.

Menstrual history : She has P3L3 and FTND, 1st childbirth was at the age of 22 years. Menarche starts at 13 years and Menopause at the age of 47 years.

Clinical Findings: On arrival, she was Afebrile, pulse was 96 beats/ min, Respiratory rate was 18 breath /min and Blood pressure 130 / 80 MMHG, the patient was conscious, cooperative, well oriented to time, place, and person. She looks anxious, febrile, & all vital parameters are normal and thin body built, and hygiene is not maintained properly. Her weight was 63 kg and her height was 1.55 m with a body mass index (BMI) of 26.3 kg/m2. Her neurological, chest examination - left breast –a lump of size 7 × 6 cm behind NAC, lump feel hard, non-tender, mobile. Left axilla – single lymph node of size 1X1 cm in the central group. Right breast normal and abdominal findings were normal. Pain present and restricted movement of the right shoulder.

Timeline: She is alright 1 year back when she started getting pain in her left breast. The pain was insidious in onset, intermittent and dull aching type no aggravating or relieving factors for the same. The patient also complained of a lump in the left breast for 9 months. It was insidious in onset and initially of a smaller size and has progressed to its present size. 1 month before their visit to a private hospital for the same complaint, after investigation report such as left breast FNAC and mammography showing breast cancer. Now she came to further treatment of that and was admitted female surgery ward in AVBRH on 05/10/2021 after investigation doctor advise her surgery and on 22/10/2021 her left side mastectomy and axillary lymph node dissection surgery was done. Now she taking further treatment at our hospital.

Diagnostic Assessments: After General history, physical examination, Blood investigations were also done hemoglobin 13.8gm, WBC Count 13800cu.mm is increased, total platelet count was is 3.61 RBS- glucose plasma random 96%, total protein was 7.5 g/DL, albumin was 4.3 g/DL, LDH level was 209 U/L, Kidney Function Test –urea 19 mg/dl, creatinine 0.7 mg/dl, Potassium 4.9 mmol/L, Sodium 144 mmol/L, urine exam. (Routing) urine albumin was nil, pus cell 0-1 cells/hpf & epithelial cell was 1-2 cells/hpf, sugar nil, HBcAg negative, HCV & HIV also negative. Coagulation profile – APTT –control was 29.50, APTT –patient 29.70, prothrombin time – control & patient was 11.90. ECG was normal. Colour Doppler USG Per Breast with Bilateral Axilla - the report is well defined heterogeneously hypoechoic lesion measuring 3.5 × 3.3 cm noted in left breast posterior to nipple-areola complex with irregular margins Calcification, mild to moderate vascularity. S/o neoplastic etiology, BIRADS - 4. USG per abdomen report was no obvious abnormality noted in the present scan. Digital Laser X-Ray Mammography & Mammography of Both Breast- shows evidence of hyper dense, irregular, nodular mass lesion is seen at 1to 2 o'clock inner location of left breast, measuring 3.6 cm × 2.8 cm × 3.2 cm in dimension. Margins are irregular. Micro calcific foci are seen within. Appears moderately vascular on color Doppler examination. Features suggestive of? Malignant etiology (Figure 1).

FNAC from lump in the left breast (microscopic finding) smear: Are cellular revealing scattered cells as well as non-cohesive clusters of moderately pleomorphic cells. Few cells show moderate to severe nucleomegaly. Few cells show nuclear irregularity with prominent nucleoli. The cytoplasm is scant to moderate. The background shows granular debris and blood.

Impression : - Breast lesion appears to be malignant,

Cytopathology examination: Smear show sheet of dyscohesive epithelial cell, few of the cell sheet shows the formation of ducts and dissociated cell population. Cell carry enlarged moderately to marked pleomorphic nuclei. A few nuclei with standout nucleomegaly, nucleation, and rare mitosis. Chromatin is granular but uneven, cytoplasm is modes to ample. A rare tumor giant cell is evident. The background shows sparse lymphocytes, atypical, smudged nuclei, and tumor necrosis. Present cytomorphological features suggestive of ductal carcinoma-poorly differentiated.

Histopathology examination: TRU CUT Biopsy from left breast lump- section from given tissue pieces shows histopathology features suggestive of invasive ductal carcinoma of the breast.

Diagnostic challenges: No challenging during diagnostic evaluation.

Diagnosis : After a physical examination and investigation doctor diagnosed a case of carcinoma of the left breast for that left side mastectomy and axillary lymph node dissection surgery was done.

Prognosis: After 10 years, 81.2 percent of women who had a double mastectomy& 79.9% of women who had a single mastectomy were still living.

Therapeutic interventions : Medical and surgical management was provided to the patient. The initial care of the patient was with intravenous normal saline, to correct dehydration. Surgical sidedressing did, Inj Cefixime 1 Gm Bd, Tab. Pan 40 Mg Od, Tab Dolo 650 Mg Sos. Syp. Orofer Xt 2tsf Bd, Syp. Lupizyme 2tsf Bd, Protein Powder 2 Tsf, Tds, Syp Duphalac 20 Ml Hs, Steam Inhalation Tds , Nebulization With Normal Saline Tds ,Tab. Diclomol Sp Bd, Tab. Limcee Od, Cap. Becosule Od, Spirometer, Chest Physiotherapy, Strict input, and output chart monitoring, TPR charting 6 hourly, blood pressure monitoring of the patient.

A 58 years old female patient was admitted to the female surgery ward with a complaint of pain in the left breast for 1 year and a lump in the left breast for 9 months after all the history & physical examination and all necessary investigation carried out and diagnosed the carcinoma of the left breast. For further treatment of that doctor advice the surgery and on 22/10/2021 left-sided mastectomy with axillary lymph node dissection surgery was done in this case report Early detection of breast cancer and necessary treatment was taken for better outcome Early detection of breast cancer remains the best defense for preventing the development of this life-threatening disease. Tumors that are smaller and nonpalpable are more treatable and have a better prognosis. [ 10 - 12 ].

Breast cancer risk has been associated with age at menarche, menopause, and first pregnancy in multiple studies. Menarche before the age of 14 years raises the risk of breast cancer by a factor of 1.1 to 1.9 when compared to menarche after the age of 14 [ 14 , 15 ]. Similarly, late menopause raises the risk of breast cancer, with women who go through menopause before the age of 45 having roughly half the breast cancer rate of women who go through menopause beyond the age of 55 [ 16 - 18 ].

Informed consent: Before taking this case, information was given to the patients and theirs, and informed consent was obtained from the patient as well as relatives.

Breast cancer is a disease in which cells in the breast grow out of control, and invasive ductal carcinoma is a type of cancer in which cancer cells start in the ducts and then spread to other sections of the breast tissue. In this case, the patient have breast carcinoma of the left breast after mastectomy of the left breast and axillary lymph node dissection was done and after taking treatment patient's condition was improved.

Conflict of Interest

No conflict of Interest

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• Grunfeld EA, Ramirez AJ, Hunter MS, Richards MA. Women's knowledge and beliefs regarding breast cancer. Br J Cancer. 2002; 86(9):1373-8.
• Selvy PT, Palanisamy V, Purusothaman T. An Improved GA-MILSVM classification approach for diagnosis of breast lesions from stain images. Int J Adv Eng Technol. 2012; 4(2):216.
• Patlak M, Nass SJ, Henderson IC, Lashof J. Mammography and beyond: developing technologies for the early detection of breast cancer. NAP.
• Gambardella C, Clarizia G, Patrone R, Offi C, Mauriello C, Romano R, et al. Advanced hemostasis in axillary lymph node dissection for locally advanced breast cancer: new technology devices compared in the prevention of seroma formation. BMC Surgery. 2019;18(1):1-9.
• Youlden DR, Cramb SM, Dunn NA, Muller JM, Pyke CM, Baade PD. The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer Epidemiol. 2012;36(3):237-48.
• Manoharan N, Nair O, Shukla NK, Rath GK. Descriptive epidemiology of female breast cancer in Delhi, India. Asian Pacific journal of cancer prevention: APJCP. 2017;18(4):1015.
• Gupta A, Shridhar K, Dhillon PK. A review of breast cancer awareness among women in India: Cancer literate or awareness deficit?. European J Cancer. 2015;51(14):2058-66.
• Ruder EH, Dorgan JF, Kranz S, Kris-Etherton PM, Hartman TJ. Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence. Clinical breast cancer. 2008;8(4):334-42.
• Aditi G., Samarth S., Sunita V., Sourya A., Miheer J., Kumbhare J.M. Utility of microvessel density and it’s correlation with nottingham prognostic index in carcinoma breast. J Pharm Res Int. 2019;11:2013–2017.
• Daga, S., Phatak, S., Khan, S., Rawekar, S., 2018. Axillary galactocele of ectopic breast: Ultrasound and mammography correlation. Medical J Dr. D.Y. Patil Vidyapeeth. 242–244.
• Dawande P, Bhatt N, Noman O, Bahadure S, Bhake A, Bhatt, N. Corelation between cytological and histological grading of breast cancer and its utility in patient’s management. Int J Curr Res. 12, 71–76.
• Domkunti R, Lamture YR, Rinait A, Gode D. Breast carcinoma in axillary tail of spence: A rare case report. Int J Curr Res. 2020; 12:92–95.
• Hemant, L.H., Keshao, H., Sunita, V., Gode, C.S., 2019. Correlation of total serum LDH levels with differentiation of breast carcinoma. Int J Curr Res. 11, 1211–1215.
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Author Info

Citation: Umare H, Ganeshpur B, Umate R, (2021) A Case Report of 58-Year-Old Female with Breast Cancer after Mastectomy of Left Breast and Axillary Lymph Node Dissection. J Hematol Thrombo Dis 9:469. DOI: 10.24105/2329-8790.2021.9.469

Received: 30-Nov-2021 Accepted: 14-Dec-2021 Published: 21-Dec-2021

Copyright: © 2021 Umare H, et al. This is an open access article distributed under the term of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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Doctoral Dissertations and Projects

Triple-negative breast cancer survivors: post-traumatic stress disorder, post-traumatic growth, quality of life, and unmet mental health needs.

Carla Horton Gray , Liberty University Follow

School of Behavioral Sciences

Doctor of Philosophy in Psychology (PhD)

Natalie Hamrick

PTSD, breast cancer, hormone-fed breast cancer, triple-negative breast cancer, TNBC, depression, anxiety, chemotherapy, survivor

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Recommended citation.

Gray, Carla Horton, "Triple-Negative Breast Cancer Survivors: Post-Traumatic Stress Disorder, Post-Traumatic Growth, Quality of Life, and Unmet Mental Health Needs" (2024). Doctoral Dissertations and Projects . 5903. https://digitalcommons.liberty.edu/doctoral/5903

The purpose of this mixed-method study was to investigate levels of PTSD, PTG, QOL, their relationships, and unmet mental health needs of triple-negative breast cancer survivors diagnosed between stages 2b-4 and 2-5 years post-treatment. Participants were recruited through two cancer organizations, breast health navigators, TNBC support groups, and online breast cancer support groups. Sixty-one participants completed the PTSD Checklist-Civilian Version (PCL-C), Post-Traumatic Growth Inventory, and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Thirty participants completed the optional short answer questions about unmet mental health needs. Participants’ mean score of 48 (SD=12.22) on the PCL-C was higher than 44, PTSD scores above 44 are considered indicative of PTSD (t(60) 2.38, p = 0.02), according to the Department of Veteran Affairs. Participants had moderate levels of PTG and moderate levels of QOL. Compared to the published sample of TNBC patients during treatment, this sample of TNBC survivors 2-5 years post-treatment had lower total QOL (M = 80.67,SD = 19.88) (t(60) =-3.70, p < .001), as well as lower QOL for all subscales. Lower PTSD (b = -1.15, p < .001) and higher PTG (b = -1.15, p < .001) both predicted higher total QOL. The qualitative short answer questions revealed important themes for mental health like the need for therapy and counseling, lack of information and support, and lack of understanding, care, and information on the transition into survivorship. Anxiety and fear of recurrence were the top reported mental health challenges. Mental health symptoms of depression, anxiety, and the need for support were identified as unmet mental health needs currently, which supports current research’s future application of prevention, identification, and interventions or treatments.

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• Published: 03 August 2024

Breast cancer clinical trial participation among diverse patients at a comprehensive cancer center

• Emily L. Podany   ORCID: orcid.org/0000-0002-9700-3616 1 , 2 ,
• Shaun Bulsara 1 ,
• Katherine Sanchez 1 ,
• Kristen Otte 1 ,
• Matthew J. Ellis 1 , 3 &
• Maryam Kinik 1  

npj Breast Cancer volume  10 , Article number:  70 ( 2024 ) Cite this article

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This study was designed to determine the enrollment patterns in breast cancer clinical trials (CCTs) of patients with diverse backgrounds in an equal access setting and to evaluate the factors contributing to low rates of clinical trial accrual in patients of low socioeconomic status (SES). We performed a retrospective review of a prospectively maintained database of new patients seen at the Dan L. Duncan Comprehensive Cancer Center dating from 5/2015 to 9/2021, which included 3043 patients screened for breast CCTs. We compared the rate of CCT availability, eligibility, and enrollment between two patient populations: Smith Clinic, where most patients are of low SES and uninsured, and Baylor St. Luke’s Medical Center (BSLMC) with mostly predominantly insured, higher income patients. We performed logistic regression to evaluate whether differences in age, clinic, race, trial type, and primary language may be underlying the differences in CCT enrollment. More patients were eligible for CCTs at Smith Clinic (53.7% vs 44.7%, p  < 0.001). However, Smith Clinic patients were more likely to decline CCT enrollment compared to BSLMC (61.3% declined vs 39.4%, p  < 0.001). On multivariate analysis, Black patients had a significantly higher rate of CCT refusal overall (OR = 0.26, 95% CI 0.12–0.56, p  < 0.001) and BSLMC only (OR = 0.20, 95% CI 0.060–0.60, p  = 0.006). Our data shows that it is likely an oversimplification to assume that equal access will lead to the elimination of CCT disparities. Efforts to diversify CCTs must include consideration of structural and institutional inequities as well as social needs.

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Introduction.

Black cancer patients in the United States have both increased overall cancer mortality and increased cancer-specific mortality 1 , 2 , 3 . In breast cancer, Black women have a 41% higher risk of dying from breast cancer when compared with White women and present on average at a later stage 2 , 4 , 5 . Structural inequities pertaining to access to care, diagnosis timing, and treatment delay affect Black women disproportionately 6 , 7 . While these are socioeconomic predictors of the observed poor outcomes, it is also well documented that Black women have a higher incidence of more aggressive breast cancer subtypes (i.e., triple negative breast cancer (TNBC)) than any other ethnic or racial groups 8 . It is critical to understand the biological basis of the observed poor outcomes of breast cancer among Black women. As we work to design precision-driven interventions for prevention, timely diagnosis, and treatment, achieving cancer health equity is not feasible without improving diversity in cancer clinical trials (CCTs).

In an ideal world, the populations studied in CCTs would be representative of the diversity of patients seen in clinic, and CCTs would be used as a tool to decrease inequity. Unfortunately, well-documented disparities exist within CCTs. The National Institutes of Health (NIH) Revitalization Act of 1993 aimed to increase the number of women and underrepresented racial groups in clinical research through mandated inclusion, yet numbers remain low 9 . In 2014, only approximately 1% of NCI-sponsored clinical trials were primarily focused on racial and ethnic minorities 10 . Studies have shown that the average enrollment of Black Americans in CCTs is at best between 5 and 7%, despite Black Americans making up more than 13% of the general population of the United States 11 , 12 , 13 .

When access to CCTs is not a barrier to enrollment, the rate of clinical trial participation by racial and ethnic minorities, especially those of low SES, has not been well studied. Data often comes from safety-net hospitals or private institutions, but rarely are both serving the same catchment area. The Dan L. Duncan Comprehensive Cancer Center (DLDCCC) in Houston, Texas provides access to breast CCTs at two clinical sites: Smith Clinic (SC), within the safety-net Harris Health System, and Baylor St. Luke’s Medical Center (BSLMC). We hypothesized that the racial and socioeconomic gap in clinical trial enrollment would be at least partially improved by similar access to breast CCTs at the two sites.

Eligibility for CCTs

Of the 3043 patients screened for breast CCTs, 366 patients were found to be eligible for CCT, and some patients were eligible for multiple CCTs. There were 431 total offers to CCTs (Fig. 1 ).

We identified 3043 new patients seen at DLDCC clinical sites between 5/2015 and 9/2021, 366 of whom were eligible for CCT. The majority of patients at each site were eligible for neoadjuvant trials and patients were often eligible for more than one CCT.

The patient demographics of the 3043 new patients seen at the DLDCCC and screened for breast CCT eligibility from 5/2015 to 7/2021 are shown in Table 1 . Notably, 50% of these patients were White at BSLMC in comparison to 11% at SC, and 74% listed English as their primary language at BSLMC versus 47% at SC. Patients at SC were on average younger, and more frequently presenting with TNBC compared to BSLMC.

More patients at SC had a trial available to them (752/1400, 53.7%) versus at BSLMC (734/1643, 44.7%, p -value < 0.001) (Table 1 ). Patients at SC were also more likely to be eligible for CCTs (191/1400, 13.6%) than patients at BSLMC (175/1643, 10.7%, p -value = 0.011).

Enrollment patterns in CCTs

Despite higher eligibility, patients at SC were less likely to accept these CCT offers (74/191 accepted, 38.7%) than patients at BSLMC (106/175 accepted, 60.6%, p-value < 0.001) (Table 1 ). This difference in acceptance was significant on univariate but not multivariate analysis (Table 2 ). Age was not found to be significantly associated with trial enrollment.

Univariate analysis of the patients showed that Black patients, Hispanic/Latino patients, and Spanish speaking patients were significantly more likely to decline CCT participation. However, on overall multivariate analysis, only the Black patient category was associated with significantly higher rate of enrollment refusal (odds ratio (OR) = 0.26, 95% CI 0.12–0.56, p  < 0.001). (Table 2 ) On the multivariate analyses across the two clinical sites, patients were significantly more likely to accept biobanking trials than other trial types at SC (OR = 16.90, 95% CI 2.13–363.77, p  = 0.018) and at BSLMC (OR = 20.10, 95% CI 3.37–395.53, p -value = 0.007). Patients at SC were also more likely to enroll into preventive trials (OR = 7.88, 95% CI 1.53–59.39, p-value = 0.020). Primary language was not found to be a determining factor in trial enrollment or refusal at either site. Black patients at BSLMC were less likely to enroll in CCTs (OR = 0.20, 95% CI 0.060–0.60, p  = 0.006) on multivariate analysis, however this was not significant on multivariate analysis in the SC subset (OR = 0.41, 95% CI 0.11–1.53, p = 0.180). (Supplemental Tables 1 and 2 ).

While patients at SC have equal opportunity when it comes to access to clinical trials, trial enrollment is only at 37% in this clinic site, compared to BSLMC clinic where over 61% of trial eligible patients consent to enrollment. Overall, Black patients were less likely to consent to trial enrollment, and the rate of trial refusal was lowest for biobanking trials across both sites and preventive trials at SC compared to other trials. Speaking a primary language other than English was not found to be a major barrier to enrollment in our population.

Our data shows that it is likely an oversimplification to assume that equal access will lead to a complete elimination of CCT disparities. At SC, which serves a more diverse population with a higher percentage of low income and uninsured patients, the patients were significantly more eligible for breast CCTs. As noted in Table 1 , patients at SC had a higher rate of TNBC (29.3% versus 14.3% at BSLMC), which we hypothesize may be one reason for the higher rate of eligibility. More SC patients were eligible for neoadjuvant trials and biobanking trials than at BSLMC (Fig. 1 ), possibly also due to the higher TNBC rates in this population.

Despite the higher rate of eligibility at SC, these patients were significantly more likely to decline the CCT. Our findings in a highly racially and ethnically diverse patient population supports the literature that shows that Black patients are less likely to agree to participate in clinical trials. The causes of discrepancy between eligibility and enrollment are multifactorial and complex. Studies have shown equal willingness among patients of different races to participate in clinical trials 14 , 15 , 16 , 17 , yet disparities in enrollment persist. In 2008, Ford 18 identified three categories of reasons for low accrual: awareness, opportunity, and acceptance/refusal barriers or promoters.

Awareness barriers include lack of knowledge about the purpose and availability of CCTs 13 , 19 . Cancer health literacy has been found in some studies to be significantly lower in Black patients 14 , 20 , 21 , though others found that the role of factual knowledge did not make a significant difference in accrual 22 . The FDA in 2020 published guidelines and potential approaches to increase the diversity of clinical trial populations, including making diversity of enrollment a priority, involving the community, and educating potential participants 23 . When CCTs do not recruit a diverse patient population and fail to be made available to racial or ethnic minorities 17 , the results cannot be assumed to be generalizable to the community at large.

Opportunity barriers include limitations due to socioeconomic status and ineligibility. Research has shown us that CCT participants are less likely to be Black and more likely to be of a higher socioeconomic status 24 , 25 , 26 , 27 , 28 . Black patients are more likely to be deemed ineligible for clinical trials 13 , 16 , 29 . This is partially due to a higher rate of comorbidities such as hypertension, vision loss, or diabetes, as well as benign neutropenia—a condition that has not been shown to increase risk of infection 16 . However, studies have also shown that Black Americans are more likely to be deemed ineligible due to perceived noncompliance or mental status, and that subjective judgements on eligibility more often favor White patients 29 .

Barriers to acceptance include an understandable mistrust in a medical system that has historically caused harm to people of color, perceived financial burden, logistical difficulties including transportation, and family or cultural pressures. When Black American patients are asked about their reasons for opting out of CCT, studies show us that a lack of trust is one of the most common factors influencing their decision 13 , 22 . Barriers relating to logistics or finances are seen more often in safety-net hospitals and clinics 19 .

At BSLMC, where the population is less diverse, we noted a difference in CCT enrollment by race in multivariate analysis. However, this finding was not significant at SC, which has a more diverse population (Supplemental Tables 1 and 2 ). This is an interesting exploratory finding that can be further elucidated in future studies but may point to more diverse clinic experiences encouraging CCT enrollment. This could be due to higher trust in the clinic, awareness of clinical trials, or physicians offering trials more equitably. A limitation of our finding is the low number of patients in each category, and future studies would need to clarify these findings with a larger patient population.

Although it is imperative that we continue to shine a light on these important issues, we must be ready to envision and enact both local and national policy changes. Moving forward, we are focusing on community engagement, patient education, and dialogue with our patients to explore specific interventions designed to improve our Black patient population’s views of trial enrollment. Interventions have been attempted around the country to varying levels of success, including patient navigation systems 30 , 31 , 32 , patient education videos 12 , 13 , the recent ACCURE trial which included multiple levels of intervention including electronic medical record changes and specific physician roles 33 , diversifying staff, ensuring trial resources are in multiple languages, and offering financial incentives 23 . The reason for trial refusal was unfortunately not uniformly captured in the clinical trial database nor in patients’ electronic medical records. This is a limitation of our study; we do not have specific patients’ refusal reasons. In a follow up study that is currently being conducted, we have designed a patient education intervention to collect specific information on patients’ attitudes towards clinical trial enrollment and refusal. This follow-up study will serve as a roadmap for designing patient and community targeted outreach programs to improve our trial enrollment.

Cancer clinical trials have maintained restrictive eligibility criteria that inevitably censor out a large population of patients 34 . It is crucial that efforts continue on all fronts to improve cancer clinical trial diversity, including clinical trial design and challenging long-standing beliefs on eligibility criteria. Prevention and treatment alike need to be considered when designing an equitable future for cancer care, and as others have shown, these efforts must include consideration of structural and institutional inequities as well as social needs. Research and data collection are only the first steps in a necessary journey toward equity in cancer care.

Study population and data collection

This is a retrospective cohort study of new patients seen from 5/2015 to 9/2021, which included 3043 patients screened for breast CCTs at DLDCCC clinical sites. The populations receiving care at the two clinical sites differ greatly. At SC, half of the patients earn less than $25,000 annually, 60% are uninsured and use a county financial assistance program known as the “Gold Card,” and 65% are not proficient in English. Fifty-nine percent of SC patients self-identify as Hispanic and 29% self-identify as Black, with White patients making up 10% of the population. At BSLMC, over 95% of the patients have federal and commercial insurance and 68% are White, 13% are Black, and 3% are Hispanic. We collected information on age at the time of screening for CCTs, patient-reported race, and primary spoken language.

The study was conducted according to the ethical guidelines set forth in the Declaration of Helsinki and in concordance with the Heath Insurance Portability and Accountability Act. The study was approved by the institutional review board (IRB) of Baylor College of Medicine. The requirement of patient informed consent was waived by the IRB as the data was deidentified prior to analysis.

DLDCCC is an active participant in several cooperative group consortia including the Translational Breast Cancer Research Consortium (TBCRC), Southwest Oncology Group (SWOG), and NRG oncology (from the parental organizations of NSABP, RTOG, and GOG), and it is frequently the leading site for national investigator initiated clinical trials (IIT). We collected information on whether there were trials available for the patients’ diagnosis, trial eligibility, and the type of trial the patients were screened for. We designated 5 categories of trials based on the intent of the trial (e.g., scalp cooling trial to prevent chemotherapy-associated hair loss) and the stage of therapy that the trial was offered (e.g., COMPASS RD, an adjuvant trial). The categories were preventive, neoadjuvant, adjuvant, metastatic, and biobanking. The same CCTs were open at both sites under the DLDCCC.

Statistical analysis

We first performed Chi-square tests to determine whether there were differences in trial availability, trial eligibility, and trial acceptance rate according to DLDCCC clinical sites. We then performed univariate and multivariate logistic regression to evaluate whether differences in age, clinic site, race, trial type, and primary language may be underlying the observed differences in CCT enrollment rates. We performed logistic regression on the overall dataset as well as by clinic. We calculated odds ratios with 95% confidence intervals to measure the strength of association between the predictors and enrollment. P-values less than 0.05 were considered statistically significant. Analysis was performed using R version 4.1.0.

Data availability

The participants in this study did not give written consent for their data to be shared. Due to the clinical nature of the dataset, it is not available publicly.

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Acknowledgements

This work was not funded. This work has previously been presented in part in poster format at the San Antonio Breast Cancer Symposium in December 2021 and the ASCO QI symposium in October 2022, as well as in an online-only abstract at the 2022 ASCO meeting in June 2022. We would like to acknowledge and thank all the patients whose deidentified data was used in this study.

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Emily L. Podany, Shaun Bulsara, Katherine Sanchez, Kristen Otte, Matthew J. Ellis & Maryam Kinik

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E.P. performed data collection, data cleaning, data analysis, and wrote the manuscript. S.B. performed data analysis and reviewed the manuscript. K.S. performed data cleaning and reviewed the manuscript. K.O. performed data collection and reviewed the manuscript. M.E. performed data collection and reviewed the manuscript. M.K. performed data collection, data cleaning, study planning, IRB submission, data analysis, and reviewed the manuscript.

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Podany, E.L., Bulsara, S., Sanchez, K. et al. Breast cancer clinical trial participation among diverse patients at a comprehensive cancer center. npj Breast Cancer 10 , 70 (2024). https://doi.org/10.1038/s41523-024-00672-0

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Breast cancer patient experiences through a journey map: A qualitative study

Laura ciria-suarez.

1 Clinical Psychology and Psychobiology Department, Faculty of Psychology, University of Barcelona, Barcelona, Spain

Paula Jiménez-Fonseca

2 Medical Oncology Department Hospital Universitario Central of Asturias, Oviedo, Spain

María Palacín-Lois

3 Social Psychology and Quantitative Psychology Department, Faculty of Psychology, University of Barcelona, Barcelona, Spain

Mónica Antoñanzas-Basa

4 Medical Oncology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain

Ana Fernández-Montes

5 Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain

Aranzazu Manzano-Fernández

Beatriz castelo.

6 Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain

Elena Asensio-Martínez

7 Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain

Susana Hernando-Polo

8 Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain

Caterina Calderon

Associated data.

Relevant anonymized data excerpts from the transcripts are in the main body of the manuscript. They are supported by the supplementary documentation at 10.1371/journal.pone.0244355 .

Breast cancer is one of the most prevalent diseases in women. Prevention and treatments have lowered mortality; nevertheless, the impact of the diagnosis and treatment continue to impact all aspects of patients’ lives (physical, emotional, cognitive, social, and spiritual).

This study seeks to explore the experiences of the different stages women with breast cancer go through by means of a patient journey.

This is a qualitative study in which 21 women with breast cancer or survivors were interviewed. Participants were recruited at 9 large hospitals in Spain and intentional sampling methods were applied. Data were collected using a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data were processed by adopting a thematic analysis approach.

The diagnosis and treatment of breast cancer entails a radical change in patients’ day-to-day that linger in the mid-term. Seven stages have been defined that correspond to the different medical processes: diagnosis/unmasking stage, surgery/cleaning out, chemotherapy/loss of identity, radiotherapy/transition to normality, follow-up care/the “new” day-to-day, relapse/starting over, and metastatic/time-limited chronic breast cancer. The most relevant aspects of each are highlighted, as are the various cross-sectional aspects that manifest throughout the entire patient journey.

Conclusions

Comprehending patients’ experiences in depth facilitates the detection of situations of risk and helps to identify key moments when more precise information should be offered. Similarly, preparing the women for the process they must confront and for the sequelae of medical treatments would contribute to decreasing their uncertainty and concern, and to improving their quality-of-life.

Introduction

Breast cancer is the most common cancer and the one that associates the highest mortality rates among Spanish women, with 32,953 new cases estimated to be diagnosed in Spain in 2020 [ 1 ]. Thanks to early diagnosis and therapeutic advances, survival has increased in recent years [ 2 ]. The 5-year survival rate is currently around 85% [ 3 , 4 ].

Though high, this survival rate is achieved at the expense of multiple treatment modalities, such as surgery, chemotherapy, radiotherapy, and hormone therapy, the side effects and sequelae of which can interfere with quality-of-life [ 5 ]. Added to this is the uncertainty surrounding prognosis; likewise, life or existential crises are not uncommon, requiring great effort to adjust and adapt [ 6 ]. This will not only affect the patient psychologically, but will also impact their ability to tolerate treatment and their socio-affective relations [ 7 ].

Several medical tests are performed (ultrasound, mammography, biopsy, CT, etc.) to determine tumor characteristics and extension, and establish prognosis [ 8 ]. Once diagnosed, numerous treatment options exist. Surgery is the treatment of choice for non-advanced breast cancer; chemotherapy, radiotherapy, and hormone therapy are adjuvant treatments with consolidated benefit in diminishing the risk of relapse and improving long-term survival [ 9 ]. Breast cancer treatments prompt changes in a person’s physical appearance, sexuality, and fertility that interfere with their identity, attractiveness, self-esteem, social relationships, and sexual functioning [ 10 ]. Patients also report more fatigue and sleep disturbances [ 11 ]. Treatment side effects, together with prognostic uncertainty cause the woman to suffer negative experiences, such as stress in significant relationships, and emotions, like anxiety, sadness, guilt, and/or fear of death with negative consequences on breast cancer patients’ quality-of-life [ 10 , 12 ]. Once treatment is completed, patients need time to recover their activity, as they report decreased bodily and mental function [ 13 ], fear of relapse [ 14 ], and changes in employment status [ 15 ]. After a time, there is a risk of recurrence influenced by prognostic factors, such as nodal involvement, size, histological grade, hormone receptor status, and treatment of the primary tumor [ 16 ]. Thirty percent (30%) of patients with early breast cancer eventually go on to develop metastases [ 17 ]. There is currently no curative treatment for patients with metastatic breast cancer; consequently, the main objectives are to prolong survival, enhance or maintain quality-of-life, and control symptoms [ 17 , 18 ]. In metastatic stages, women and their families are not only living with uncertainty about the future, the threat of death, and burden of treatment, but also dealing with the existential, social, emotional, and psychological difficulties their situation entails [ 18 , 19 ].

Supporting and accompanying breast cancer patients throughout this process requires a deep understanding of their experiences. To describe the patient’s experiences, including thoughts, emotions, feelings, worries, and concerns, the phrase “patient voice” has been used, which is becoming increasingly common in healthcare [ 20 ]. Insight into this “voice” allows us to delve deeper into the physical, emotional, cognitive, social, and spiritual effects of the patient’s life. This narrative can be portrayed as a “cancer journey", an experiential map of patients’ passage through the different stages of the disease [ 21 ] that captures the path from prevention to early diagnosis, acute care, remission, rehabilitation, possible recurrence, and terminal stages when the disease is incurable and progresses [ 22 ]. The term ‘patient journey’ has been used extensively in the literature [ 23 – 25 ] and is often synonymous with ‘patient pathway’ [ 26 ]. Richter et al. [ 26 ] state that there is no common definition, albeit in some instances the ‘patient journey’ comprises the core concept of the care pathway with greater focus on the individual and their perspective (needs and preferences) and including mechanisms of engagement and empowerment.

While the patient’s role in the course of the disease and in medical decision making is gaining interest, little research has focused on patient experiences [ 27 , 28 ]. Patient-centered care is an essential component of quality care that seeks to improve responsiveness to patients’ needs, values, and predilections and to enhance psychosocial outcomes, such as anxiety, depression, unmet support needs, and quality of life [ 29 ]. Qualitative studies are becoming more and more germane to grasp specific aspects of breast cancer, such as communication [ 27 , 30 ], body image and sexuality [ 31 , 32 ], motherhood [ 33 ], social support [ 34 ], survivors’ reintegration into daily life [ 13 , 15 ], or care for women with incurable, progressive cancer [ 17 ]. Nevertheless, few published studies address the experience of women with breast cancer from diagnosis to follow-up. These include a clinical pathway approach in the United Kingdom in the early 21st century [ 35 ], a breast cancer patient journey in Singapore [ 25 ], a netnography of breast cancer patients in a French specialized forum [ 28 ], a meta-synthesis of Australian women living with breast cancer [ 36 ], and a systematic review blending qualitative studies of the narratives of breast cancer patients from 30 countries [ 37 ]. Sanson-Fisher et al. [ 29 ] concluded that previously published studies had examined limited segments of patients’ experiences of cancer care and emphasized the importance of focusing more on their experiences across multiple components and throughout the continuum of care. Therefore, the aim of this study is to depict the experiences of Spanish breast cancer patients in their journey through all stages of the disease. To the best of our knowledge, there are no studies that examine the experience of women with breast cancer in Spain from diagnosis through treatment to follow-up of survivors and those who suffer a relapse or incurable disease presented as a journey map.

A map of the breast cancer patient’s journey will enable healthcare professionals to learn first-hand about their patients’ personal experiences and needs at each stage of the disease, improve communication and doctor-patient rapport, thereby creating a better, more person-centered environment. Importantly, understanding the transitional phases and having a holistic perspective will allow for a more holistic view of the person. Furthermore, information about the journey can aid in shifting the focus of health care toward those activities most valued by the patient [ 38 ]. This is a valuable and efficient contribution to the relationship between the system, medical team, and patients, as well as to providing resources dedicated to the patient’s needs at any given time, thus improving their quality of life and involving them in all decisions.

Study design and data collection

We conducted a qualitative study to explore the pathway of standard care for women with breast cancer and to develop a schematic map of their journey based on their experiences. A detailed description of the methodology is reported in the published protocol “Ascertaining breast cancer patient experiences through a journey map: A qualitative study protocol” [ 39 ].

An interview guide was created based on breast cancer literature and adapted with the collaboration of two medical oncologists, three nurses (an oncology nurse from the day hospital, a case manager nurse who liaises with the different services and is the ‘named’ point of contact for breast cancer patients for their journey throughout their treatment, and a nurse in charge of explaining postoperative care and treatment), and two psycho-oncologists. The interview covered four main areas. First, sociodemographic and medical information. Second, daily activities, family, and support network. Third, participants were asked about their overall perception of breast cancer and their coping mechanisms. Finally, physical, emotional, cognitive, spiritual, and medical aspects related to diagnosis, treatment, and side effects were probed. Additionally, patients were encouraged to express their thoughts should they want to expand on the subject.

The study was carried out at nine large hospitals located in six geographical areas of Spain. To evaluate the interview process, a pilot test was performed. Interviews were conducted using the interview guide by the principal investigator who had previous experience in qualitative research. Due to the Covid-19 pandemic, all interviews were completed online and video recorded with the consent of the study participants for subsequent transcription. Relevant notes were taken during the interview to document key issues and observations.

Participant selection and recruitment

Inclusion criteria were being female, over 18 years of age, having a diagnosis of histologically-confirmed adenocarcinoma of the breast, and good mental status. To ascertain the reality of women with breast cancer, most of the patients recruited (80%) had been diagnosed in the past 5 years. Patients (20%) were added who had been diagnosed more than 5 years earlier, with the aim of improving the perspective and ascertaining their experience after 5 years.

Medical oncologists and nurses working at the centers helped identify patients who met the inclusion criteria. Participants went to the sites for follow-up between December 2019 and January 2021. Eligible women were informed of the study and invited to participate during an in-person visit by these healthcare professionals. Those who showed interest gave permission to share their contact information (e-mail or telephone number) with the principal investigator, who was the person who conducted all interviews. The principal investigator contacted these women, giving them a more detailed explanation of the study and clarifying any doubts they may have. If the woman agreed to participate, an appointment was made for a videoconference.

A total of 21 women agreed to participate voluntarily in this research. With the objective of accessing several experiences and bolstering the transferability of the findings, selection was controlled with respect to subjects’ stage of cancer, guaranteeing that there would be a proportional number of women with cancer in all stages, as well as with relapses.

Data analysis

The data underwent qualitative content analysis. To assure trustworthiness, analyses were based on the system put forth by Graneheim, and Lundman [ 40 ]. Interviews were transcribed and divided into different content areas; units of meaning were obtained and introduced into each content area; meaning codes were extracted and added; codes were categorized in terms of differences and similarities, and themes were created to link underlying meanings in the categories. All members of the research team (core team, two medical oncologists, three nurses and two psycho-oncologists) reviewed the data and triangulated the outcomes between two sources of data: qualitative data from the interview and non-modifiable information, such as sociodemographic (i.e., age, marital status, having children) and clinical (i.e., cancer stage and surgery type) data. Following this process, we reached saturation of the interview data by the time we had completed 21 interviews.

Ethical considerations

This study was performed in accordance with the ethical standards of the Declaration of Helsinki, and its subsequent amendments. The study was approved by the Research Ethics Committee of University of Barcelona (Institutional Review Board: IRB00003099) and supported by the Bioethics Group of the Spanish Society of Medical Oncology (SEOM) 2018 grant. All participants received a written informed consent form that they signed prior to commencing with the interviews and after receiving information about the study.

Patient baseline characteristics

In total, 21 women with a mean age of 47 years (range, 34 to 61) were interviewed. Most of the study population was married (66.7%), had a college education (66.7%), and had 2 or more children (42.9%). All cancer stages were represented, up to 23.8% tumor recurrence, and most of the primary cancers had been resected (95.2%) (see Table 1 ).

Description of the breast cancer patient journey

The women diagnosed with breast cancer describe the journey as a process tremendously affected by the different medical stages. Each stage has its own characteristics that condition the experiences, unleashing specific physical, emotional, cognitive, and social processes. Additionally, the patients perceive this entire process as pre-established journey they must undertake to save their life, with its protocols based on the type and stage of cancer.

“ People said to me , ‘What do you think ? ’ and I answered that there was nothing for me to think about because everything is done , I have to go on the journey and follow it and wait to see how it goes” (Patient 6)

Fig 1 displays the various phases of the journey that patients with breast cancer go through; nevertheless, each woman will go through some or others, depending on their type of cancer.

Throughout the entire patient journey

Processes of loss and reinterpretation of the new circumstance . What stands out the most in the process these women go through during the diagnosis and treatment of breast cancer is loss; specifically, the loss of health and a reinterpretation of the new circumstance and the new bodily reality. In the most extreme cases, the loss of health emerges with the fear of death that many women report at the time of diagnosis or during treatment, due to the distress generated. The loss of identity seems to be related to the evolutionary (existential) moment in which the woman is; there are patients who report feelings of disability or loss of attractiveness, or fear of not being able to get pregnant in the future, especially the youngest.

I felt a terrifying fear and thought , “You have cancer you tell yourself , you’re going to die tomorrow .” (Patient 6) I feel like after the hysterectomy , as a woman , I no longer have anything , only the physical . Sure , I look great , but I tell myself that it’s just a shell , the shell I inhabit , because as a woman , I only have one breast left . (Patient 6) At that moment , I had to make the decision that I was no longer going to be a mother . (Patient 14)

Personal change . Most of the women report that with the diagnosis of breast cancer, their life stands still and from that point forward, a different journey begins. The sole focus on this journey is the disease and its implications. During all those months, the patients stop working; they focus on their medical treatments, and reflect a lot on their current situation and on life. Most of the participants state, especially those who have already been discharged, that they know themselves better now; they take better care of themselves, and they enjoy their day-to-day and the small moments more, making the most of their time, with more initiatives and fewer trivial complaints.

Clearly , you’re not the same person you were before; I don’t think she’ll ever come back; your mindset changes completely and I have sequelae from all the treatments . (Patient 1) I re-think wasting energy on lost causes; what’s more , I’ve also learnt to say no . If I’m not in the mood to go somewhere , I just say no . (Patient 7) I take much more advantage of the present now , because you realize that things can change on any given day . (Patient 3)

Trust and appreciation for their physician . Most of the interviewees stated that they fully trusted the doctors who care for them, without question or objection to the treatments proposed. They reported that, as they go forward, they discuss the tests and treatments that are going to be performed, as well as possible side effects. Several stated that they are unaware of the stage of their cancer; similarly, most also do not know the benefits expressed in X% of the treatments. A few of the participants claimed that they did talk in detail about the different types of treatments with their oncologists, that they had sought another opinion, and one of them even reported having decided to stop chemotherapy, which was very hard for her, given her physician’s insistence that she continue.

The truth is that the oncologist didn’t say much about percentages; what she told me were the steps that I had to take; I thoroughly trusted her and she gave me a lot of peace of mind . (Patient 5) I told him , “I’m going to do whatever you tell me to . ” It never occurred to me to dispute whatever the oncologist might tell me . I was willing to do whatever was needed . (Patient 8)

Most of the women, at some point during the interview, state that they are grateful for the care they received and that, within the seriousness of their situation, there is a treatment for their condition.

I am super grateful for the treatment I’ve received and with the doctors assigned to me . (Patient 2) I’m very lucky; I’m only on my second line of treatment for metastasis and I’ve got a lot more ahead of me , but I consider myself lucky and I believe things are going very well . (Patient 20)

Role of the woman . We can see that the women adopt a role of care-givers and managers of their surroundings. They worry about the disease negatively affecting the people around them, which is why they make an effort to manage the family’s activity for when they can’t do it and they try to avoid being a physical burden or cause emotional distress to the people around them.

I was very strong ; I made everything easy for people , but making it very easy , doesn’t mean that it was easy for me , but that I made it easy for everyone . (Patient 8) I didn’t want to worry anyone because that’s just the way I am , I push forward and that’s that . (Patient 5)

Support network . In all cases, the family appears to be one of the elements that is most involved in the disease process. Within the family, the partner deserves special mention. The testimonies in this regard reveal a wide spectrum of possibilities that range from the feeling of having had great support to a lack of attention and understanding that, in many situations, causes the relationship to be strained or to end. Friends tend to appear more occasionally.

I can’t complain about my husband; he was up to the challenge , very attentive toward me and he fully understood how I was feeling ; I felt very supported . (Patient 14) We’ve had a period of a lot of arguing; I’ve had to sit down with him and tell him that life had changed for me . (Patient 18) I had a partner I had lived with for five and a half years and he told me , literally , that he looked at me like a little sister , no longer as a woman , and he left me , and that hurt me tremendously . (Patient 6)

On the other hand, many patients commented on the importance of social media, where they have met people in the same situation as them. They report feeling understood and in good company; likewise, they commented on the importance of being able to share their doubts and get to know about other experiences.

It’s a situation that only someone who has gone through can understand; you can have all the good intentions in the world , but if you haven’t gone through it , you can’t even begin to understand . (Patient 8)

Use of complementary treatments . Most patients follow conventional medical treatment. However, many resort to other disciplines that help them improve their quality-of-life, like dietary changes, getting more exercise than usual, visits to a psychologist or physical therapist, or using other integrative therapies, such as acupuncture, yoga, reiki, flowers of Bach, homeopathy, cannabis, or meditation.

I started to read a whole bunch of books to see what I could do to take care of myself in terms of nutrition and exercise ; you consider everything you can do . (Patient 5)

Diagnosis/unmasking

This phase encompasses the time from when the woman detects some symptom or goes to a check-up until the medical diagnosis is made. For the woman, this is a time of a series of tests and results. We have observed that the procedures, especially the healthcare professionals that deal with the patients, and the timing vary, depending on the medical center where they are being cared for. Emotionally, this is one of the most complicated stages.

Emotional whirlwind . The wait to obtain test results has a huge emotional impact for the women, given that it is a time of great uncertainty and fear.

An entire month with all the anguish of finding out if you have something . (Patient 3) The worst part is waiting 15 days to find out the magnitude of the tragedy , if it’s throughout your entire body or only in your breast; you go through a brutal emotional whirlwind; the wait is horrible because there’s nothing else you can do , so that anguish that you carry inside is dreadful; it was hell for me . (Patient 10)

Additionally, the interviewees described many other emotions that included fear of death, fear of having no time, feeling of unreality, rage, anger, sadness, avoidance, denial…

The first thing I thought was that I was going to die and that I wouldn’t finish watching my children [grow up]; my father had died of lung cancer 25 years ago . (Patient 9) My only aim was to get back to normal , as if there were nothing wrong . (Patient 4) You have a lot of conflicting feelings; you wish this weren’t happening; you want to run away , but you say , “Where am I going to run to ? ” . (Patient 14)

Impact of medical communication . Several women comment that, when given the diagnosis, they dissociate because of the emotional impact and that they don’t listen to all the information that the medical professional is giving them.

I remember that she talked and talked , but I didn’t know what she was saying until she said , “Isabel , you’re going to be cured , okay ?”. (Patient 9)

During the diagnostic testing, the women are highly sensitive to the healthcare professionals’ words and gestures.

I looked at the face of the person who was doing the mammogram and that’s when I started to imagine the worst . (Patient 20) I say to them , “ But , is there a solution to this ? ” , and they say to me , “Don’t worry , I’m sure there is a solution . ” That “sure” is etched in my mind . (Patient 10)

Communication and managing their surroundings . After the diagnosis, the patients feel that they have to tell the people around them about their situation, especially those closest to them, the family. They all agree on how hard it is to share. Normally, the people it’s hardest to tell are their mother and their children. When they do, they try to put the most positive spin on it possible, in an attempt to keep them from worrying.

You no longer think only about yourself , you think , “Good grief , now I’ve got to tell my mother .” It’s hard . (Patient 16) I wanted to tell my kids the way I say things , always trying to look for the upside , and positive , although it was hard , but , anyway , in the end , it went well . When I finished , my husband told me , “You’ve convinced me that it’s no big deal .” (Patient 9) I told my son , “Son , don’t cry , your mom’s going to get over this , this is nothing .” (Patient 1)

During this period, the women contemplate how their situation will affect their surroundings and they try to organize it as much as possible.

I devoted myself to planning everything , to organizing what to do with my daughter , and to thinking about work , too , how I had left things at work . (Patient 4)

Surgery/cleaning out the cancer

Uncertainty and fear . The participants express that before going into surgery, they are told about the kind of procedure that will be done, but that, depending on what they find and the analysis, it may change. In light of this, they exhibit an enormous feeling of uncertainty and fear. In addition, many voice concern about how the surgery will go.

They tell you conservative surgery , but if we open up and see something we didn’t see on the tests , then everything could change . (Patient 10) Aside from the anesthesia , that I’m terrified of , you spend several hours in surgery and you don’t really know how things will go; when they clean it out , they analyze it , and you go into the operating room and you don’t know what can happen . (Patient 9)

Feeling of loss . Considering that the breast is associated with an intimate, feminine part [of their body], many women experience the operation as a loss. This loss is more acute if the operation is a mastectomy and there is no reconstruction at the same time. The loss also involves a loss of identity, compounded by the side effects of chemotherapy, such as hair loss. The interviewees who had undergone mastectomy say that following surgery, when the bandaging is removed and the scar is revealed, is one of the most critical moments, which is why they express difficulty in managing it and appreciate the caring assistance from the professionals.

It is identification with yourself , you know , it’s what you’ve seen in the mirror , what you think you’re like and , suddenly , you’re no longer like that; there’s an incredible personal crisis because you no longer recognize what you’re seeing . (Patient 11) I closed my eyes and I removed the bandaging and I didn’t dare look … with my eyes , I imagined the worst . (Patient 12)

Acceptance or demand for more aggressive intervention . The patients perceive the surgery as essential to recovering their health, which is why the process is widely accepted. Some patients who demand a more invasive intervention, normally a bilateral mastectomy, do so because that way, they feel safer with respect to a possible relapse, as well as more comfortable esthetically.

If they have to remove my breast , let them take it; what I want is to get better . (Patient 16) They say that I am in full remission , so they only removed the lump , but at first , I said that I wanted my whole [breast] removed ; then they assessed how to do it . (Patient 13) They told me that I had a genetic mutation and more possibilities of developing breast cancer and , since I felt such rejection toward my remaining breast , I decided to get rid of that one , too . (Patient 20)

Chemotherapy/loss of identity

The chemotherapy phase is one of the phases that affects the women’s lives the most, because of its physical impact and how long it lasts. No differences have been found in how they experience chemotherapy depending on whether it was neoadjuvant or adjuvant.

Negative impact of side effects . Chemotherapy is associated with many side effects that vary from one woman to another. Many indicate that they have suffered physical discomfort, such as fatigue, dysgeusia, pain, nausea and vomiting, mucositis, diarrhea, etc.

One day when I didn’t want to go to bed , I went to bed crying because I had the feeling that I wasn’t going to wake up . That day it was because I felt awful . (Patient 1)

Furthermore, all of the women suffer hair loss, which is one of the most-feared effects. Likewise, their body hair also falls out, especially on their face, and their weight fluctuates. All of these changes lead to a loss of identity that is experienced as taking away from their femininity. It must be remembered that oftentimes, chemotherapy is administered after surgery, further exacerbating this physical change. On top of all that, several women comment having to decide at the beginning of treatment whether to freeze their eggs or not; at that moment, many of them forfeit the possibility of becoming a mother or of becoming a mother again, which also adds to this loss of femininity.

Losing my hair was hard , but when it grew out again , I had an identity crisis . I didn’t recognize myself; people said I was really pretty like that , with my hair so short . I looked at myself in the mirror and I said that I’m not that woman , I can see that that woman is pretty , but it’s just that I don’t recognize myself . That’s not me or , it was like , I looked at myself and I didn’t recognize myself . That’s when I suffered a serious identity crisis , psychologically serious , but also serious because I sobbed because I looked at myself , but it wasn’t me . (Patient 6) Where’s that sexy lady , where is she ?, because you don’t feel good . I didn’t like myself at all . I was several sizes larger and I looked at myself and said , “What a monster . ” I didn’t feel good about myself . (Patient 1)

Many patients say that chemotherapy decreases their libido and dries up their mucous membranes, which is why they prefer not to have sex. For those who live as a couple, this situation can strain the relationship.

Sexually , I just didn’t feel like it , I wasn’t in the mood; not only did I not feel like it , my mucous membranes were dry and , what’s smore , I just couldn’t , I couldn’t , I felt bad for my husband , but he said , “Don’t worry .” (Patient 16)

Finally, some interviewees expressed a feeling of being poisoned by the treatment. These women tend to be highly focused on taking care of their body and have a very natural attitude toward life.

I had to really work my awareness that I was poisoning myself; at night I was at home and I thought that all that red liquid was circulating through my veins … I think I even had nightmares . (Patient 4)

Balance between caring for oneself and caring for others . The patients feel that it is time to take care of themselves, so they prioritize resting when they need it. Moreover, they worry about getting a haircut and, most of the times, they look for turbans and wigs. Some also learn how to put on make-up, which they rate as being very positive. On the other hand, those who have children or another person in their care, try to take care of them as much as they are able.

Around 11 : 00 , I no longer felt good , so I’d go to the armchair to rest and it’s like I had an angel , because I’d wake up a minute before I had to set the table and get lunch for my son who would be coming home from school . (Patient 1) While I was getting chemo , I went with the gadget and I told myself , “I’m going to teach you to apply make-up; for instance , your eyelashes are going to fall out . Make a line like this ” and at that moment when you look in the mirror , and we look like Fester in the Addams family . (Patient 13)

Vulnerability . The women experience great uncertainty and feelings of vulnerability the first times they receive chemotherapy, since they don’t know what side effects they will suffer.

With chemo , I started with a lot of fear and , later on , I became familiar with it little by little until the time comes when you go to the hospital like someone who’s going to pick up a bit of paper . (Patient 9)

In addition, those participants who join a social network or who are more closely tied to the hospital setting, know about the relapses and deaths of people around them diagnosed with breast cancer, which makes them feel highly vulnerable.

There are some people who leave the group because … it’s not like there are a lot of relapses and , geez , I think that it messes with your head . (Patient 13) We were almost always the same people at chemotherapy ; there was one guy who was really yellow who looked terrible and , there was one time when we stopped seeing him and another lady asked and the nurse said that he had died . (Patient 15)

At the same time, given the physical changes, especially those that have to do with body hair, many women feel observed when they leave home.

If I have to go out and take off my scarf because I’m hot or go straight out without any scarf on my head and whoever wants to look… let them ; I think that it’s up to us , the patients , to normalize the situation; unfortunately , there are more and more cases . (Patient 9)

Telling the kids . Since when the chemotherapy stage is going to entail many physical changes, the women look for ways to talk to their children about the treatment. Most of them comment that it is a complicated situation and all of them try to talk to their children in such a way as to protect them as much as possible.

I asked the nurse for help before I started chemotherapy to see if she had any pointers about how to talk about this with the kids and she recommended a story , but when I saw it , I didn’t like it … so , in the end , I decided to do it off the cuff . (Patient 10)

Radiotherapy/transition to normality

The “last” treatment . When the patient reaches radiotherapy, normally, they have already spent several months undergoing physically aggressive medical procedures, which is why they feel exhausted. There is a physical exhaustion resulting from the previous treatments and made worse by the radiation therapy. Furthermore, many women also report feeling emotionally drained by the entire process. However, this is generally accompanied by joy and relief because they feel that they are in the final stage of treatment.

Emotionally , it’s a marathon that has to end up at some point . (Patient 10) For me , radiotherapy was like a lull in the battle , with a winning mind-set . (Patient 4)

Comparison with chemotherapy . There is a widespread perception that radiotherapy has fewer side effects than chemotherapy, although later, when they receive it, several patients suffer discomfort, above all fatigue and dizziness. Several report that at this point, they are mentally worn out and just want to be done with the process, which is why they have less information than about chemotherapy.

I feel like radiotherapy is unknown , that you think it’s more “light ” and it turns out not to be so light . (Patient 13)

Follow-up care/the “new” day-to-day

Difficulty in getting back to normal . Once the patients are discharged, many feel that they need some time to recover, that it will be slow, in order to restore a more normalized pace of life. They are still working on their emotional and personal process.

When they tell you that you have cancer , they make it very clear : you have a goal; you have some months of chemo , some months of radio , and when you finish , you say , “And now , what do I do ?”. I say that because now I have to get back to my normal life , but I don’t feel normal . I still don’t feel cured , I’m not 100% . And you’re glad you’ve that you’ve finished it all and you’re alive , but at the same time , you say , “Gosh… this is very odd . ” It was a very strange feeling . (Patient 8)

Most patients report that their quality-of-life has diminished, due to the sequelae from the treatments. Lymphedema is one of the sequelae they name most often, although they also mention other symptoms, like digestive upset, weight issues, eye problems, scar pain, etc. The women who are on hormone therapy also suffer side effects, such as joint and muscle pain.

I have lymphedema and , although I have good mobility , I’m a little bit weak; when I go out for dinner , I generally order fish , because I can’t always cut meat well . (Patient 6)

Several interviewees also express difficulty in their affective-sexual relations. Many of them feel insecure because of all the physical changes; others have sequelae that hinder their relations, and still others are suffering symptoms of early menopause. This can cause problems in the couple and for those who don’t have a partner, suffer many complications when it comes to meeting other people.

I haven’t had sex with my husband for 2 years because , it’s also really complicated to get over; I’ve gone for pelvic physical therapy; I’ve used gels , but nothing works . (Patient 8) It’s taken me many months for me to have a relationship again; it’s been really hard because , even though everyone told me that I looked fine , I didn’t feel fine . My breast cancer had taken away all my attributes as a woman . (Patient 6)

Some women also experience difficulties when it comes to returning to work. Several state that they had been fired when they went back. They also report that when interviewing for a job, it’s complicated for them because they have to explain what happened and they mention the schedule of doctor’s visits that they have. Other women comment that they’ve been given early retirement or disability.

You go to the interview and if you tell them that you’ve had the disease , they look at you like you’re a weirdo . (Patient 13)

Breast reconstruction . How reconstruction is experienced, as well as its timing, are highly contingent upon they type of reconstruction. Each one has its pros and cons, but the opinions collected with respect to the type of reconstruction have been positive.

Although it took 18 months for the entire process to be over , I’m delighted with reconstruction with the expander . (Patient 16)

Some patients state that after the whole process, which has been long and complicated, they prefer not to undergo reconstruction immediately. In these cases, they report having felt a subtle pressure from the outside to undergo reconstruction.

Every time I went for my check-ups , they said , “You’re the only one left [who hasn’t undergone reconstruction]” and in the end , the truth is that I’m really happy because I think I look pretty . (Patient 12)

Check-ups and fear of relapse . Check-ups are one of the times that generate most worry and insecurity. The women remark that, starting a few days before and until they receive the results of the follow-up studies, they are more anxious about the possibility of relapse.

At every check-up my legs start shaking again and my stomach is in knots, although at my last one, everything turned out okay and I’m thrilled. (Patient 6) During the first stage , I did everything I had to do and I got over it , but it’s a lottery . You can do whatever you want , but it’s the luck of the draw and when you start going for check-ups , it’s like going to play Russian roulette . (Patient 8)

Maintenance hormone therapy . Hormone therapy is understood differently depending on age and on the major decision of whether or not to be a mother or to have another child. If the woman does not want to have more children, the treatment is accepted better. The patients who take it also report effects derived from menopause, for instance, joint pain or dry mucous membranes.

I did notice joint pain , but since I exercised , [I felt it] much less than my fellow women , although , for instance , when it comes to getting up from a chair , you get up like an old lady . (Patient 10)

Position of support . Several patients mention that, after discharge, they stay active on social media, they volunteer when they find out about someone or to participate in activities related to breast cancer, with the aim of being able to help other people who are in this situation.

It’s really good to meet other people who are going through the same thing , so , now that I’ve finished , I like it and I always help whenever I can , because I can share what was good for me . (Patient 13)

Relapse/starting over

Emotional impact . The diagnosis of a relapse is experienced much the same as the initial diagnosis. All of the women report fear, although they also state that they are more familiar with the processes. Other emotions emerge, such as why me, blame, disbelief, etc.

Since they had told me that it wasn’t going to happen again , I believed it , of course , I wanted to believe it and it totally surprised me; I couldn’t stop crying and crying . (Patient 17)

Telling the family again . Patients repeat that telling the family about it again, especially the children and parents, is tough and they try to minimize it in an attempt to protect them emotionally.

On the very same day that I had my mammogram , my mother says that she wants to come a see the kids . We’re in the park , when she arrives , I have to tell her that everything’s fine and when we get home , I tell her everything . My mother’s devastated again and I tell her not to worry , that everything is going to be fine . (Patient 16)

Thinking about whether something could have been done differently . Several women comment that, after their relapse, they think about whether the treatment was enough or there must have been something they could have done to avoid the relapse.

You get furious , because you say , “I wasn’t supposed to get sick , because if , 2 years ago when the first microcalcifications appeared I had had them removed , then I wouldn’t have metastasis , or maybe I would . (Patient 19)

Metastatic breast cancer/time-limited chronic

Re-interpreting the concept of metastasis . Most of the participants in this stage state that they have had to give new meaning to the word, “metastasis,” since their first perception was directly related to death. In this way, they come to understand that cancer can become chronic, although they now have to take medication and go to the hospital on a regular basis. Nevertheless, they know that their life expectancy may be a few years. The women who are involved in a group point out how hard it is to see their fellow member pass away.

What I now call my “ new normal” consists of lots of visits to the hospital and never going back to work . (Patient18)

They also state that at this stage, they do not identify with the disease generally known socially as “breast cancer”, where there is great emphasis placed on early detection and on their chances of being cured. This causes them to feel more isolated.

These pink ribbon campaigns hurt us because they tend to underscore that everything is going to turn out fine because breast cancer has a very high cure rate; there is huge lack of awareness . (Patient 20)

Physical and emotional discomfort . Most of the women in this stage report side effects from the treatments, although some comment that good quality-of-life can be preserved. On an emotional level, they say that they sometimes feel a certain agony due to not knowing how much longer the treatment will be effective. They live in a state of uncertainty that they try to cope with by focusing on their day-to-day and experience the good times deeply.

When I’m not in pain , I try not to even remember what I have and go out and have fun with my family and live . (Patient 20)

Several women who have children express with regret that they worry about their children enjoying them and remembering them when they were well. They are sad that they won’t be able to grow up in a normal family. Some also comment the impact this diagnosis is having on their partner.

What I don’t want is for them to carry this baggage of having a sick mother . (Patient 18)

A conflict with disability also appears, as many women report their desire to continue working, but feel that they can’t keep up with the pace of work. Additionally, several state that going through the medical board is a strenuous process, given that they look good physically.

It’s hard to deal with , I’m a non-practicing lawyer and I have degrees galore , but I worked the first year and I couldn’t continue . (Patient 21) Every year they call me again for the disability monitoring and they always threaten me . To be honest , the treatment doesn’t make me sick , but I don’t know how long it’s going to be like this . (Patient 19)

Social invisibility . The participants say that they do not have any physical signs of being ill, that they look fine, although they know and feel that inside, they are not well. They say that it is sometimes hard to manage socially, since on occasion, they feel misunderstood and disparaged.

I’m much sicker now , but people think or want to think that I’m fine . When I was doing chemo , it was like wearing a sign that said “cancer . ” (Patient 17)

This study describes the patient journey of women with breast cancer, specifying the different phases with the most relevant aspects of each, as well as the different cross-sectional features they report throughout the entire treatment process.

The results portray breast cancer as a process in which there is a striking feeling of loss of health and self-identity, changes in routines, personal and employment transformation, as well as emotional hardship during and after breast cancer treatment, aspects that are also reported in the literature [ 41 , 42 ]. Earlier studies state that experiencing cancer is highly stressful. It involves a major threat to life or physical integrity, in addition to mental health, interfering with the path, projects, and plans patients have for their life over the short, medium, and, on occasion, long term as well [ 6 ]. Along with reporting adverse physical and psychological impacts, patients also report positive ways in which they have grown psychologically or emotionally from the experience [ 7 , 42 ]. The diagnosis of breast cancer not only impacts the women individually, but also affects their surroundings. As reported in the literature, despite going through a very challenging time, the women struggle to put on a positive face and attempt to conserve the family’s well-being, specifically that of their children [ 7 ]. At the same time, the family is a fundamental source of support and usually provide indispensable support; however, it is not always effective, because family members do not fully understand the stresses involved in living with cancer [ 43 ]. Previous studies also reveal that for some women, their partners are one of their most significant supports; nonetheless, research also suggests that a cancer diagnosis predicts marital breakup more strongly for female survivors than males [ 44 ]. Our results reflect that the women frequently resort to other women in the same situation, possibly because they face significant unmet supportive care needs [ 30 ]. The need for social support may lead patients to seek social support groups consisting of people who are experiencing similar health crises, because such groups allow them to interact with those who best understand their suffering [ 43 ]. Another aspect that appears across the board is the relationship the participants have with the medical team. In this study, we have noted their trust in the medical team and acceptance of the treatments proposed without going into the clinical data of the disease and without needing to know the benefit provided by the treatment. Cancer patients are confronted with a potentially life-threatening [condition], feeling vulnerable, and need to rely heavily on their care providers, expecting the physician to act in their best interests [ 5 ]. Therefore, they need to have a close relationship, as well as comprehensive care [ 30 ]. Patients’ trust in a physician has been associated with a reduction of their fears and anxiety and [increased] satisfaction and adherence to treatment [ 5 , 30 ]. We believe that it would be important to provide patients with accurate information, so as to avoid misunderstandings (such as cancer being synonymous with death, regardless of stage) as several participants in this study have reported, which can lead them to believe that the risk of relapse with and without chemotherapy is much greater than the oncologists estimate [ 45 ]. We believe that in future studies that it would be worthwhile to examine the peculiarities of each kind of patient information with the aim of determining how to break it up and make it both comprehensible and tolerable to promote patients’ well-being.

A breast cancer diagnosis is generally unexpected and practically all patients suffer psychological distress, such as feelings of uncertainty, disbelief, hopelessness, vulnerability, anger, fear, anxiety, and sadness [ 46 , 47 ]. The literature has reported that many women experience peritraumatic distress or dissociation during the medical conversation in which they are given their diagnosis of cancer [ 48 ], which might account for the reactions of the respondents. Given that, when they receive their diagnosis, additional information is generally given to them, such as clinical aspects and preferred treatments. Repeating this information at subsequent appointments could contribute to improving communication with patient, since several participants stated that they found it hard to pay attention to the physician, given the emotional impact. Additionally, breast cancer patients tend to be diagnosed when they are relatively young, and often when they are in the middle furthering their career or raising children [ 12 ]. In spite of everything, the women try to put on as brave a face as they can and focus on maintaining their children’s well-being [ 7 ]. Telling children about their diagnosis is reportedly one of the biggest challenges; parents are usually unsure of how to tell them, because at the same time that they want it to be open and honest and cover their children’s developmental needs, they also want to protect them children [ 49 ].

Once diagnosed, breast cancer patients go through different treatments. The most salient experiences of these phases pertain to the impact of side effects on physical quality-of-life and psychological well-being, which is consistent with the literature [ 11 ]. Moreover, cancer therapy entails physical changes that affect their feminine identity, fertility, self-esteem, sexual functioning, and makes them more vulnerable [ 10 , 50 ]. Women described their inner self as being on an emotional rollercoaster with highs and lows throughout the various phases of treatment [ 7 ]. Given treatment side effects and sequelae, these women are more likely to experience physical symptoms and psychological disorders than patients with other kinds of tumors [ 51 ]. The side effects involve an acute sense of loss of health and quality-of-life, as well as identity and femininity. It would be interesting for future research to explore the therapies used in grief counseling with cancer patients, as understanding and exploring this perspective could comprise an additional clinical aid.

Once the women have completed their treatments, they gradually get back to normal and many contemplate returning to work. However, in line with our results, the literature reveals that even though they want to normalize their lives, female breast cancer survivors feel that they will never return to their baseline status [ 7 ]. A significant number of patients experience difficulties in physical, cognitive, and emotional functioning after their treatment, such as symptoms like lymphedema, fatigue, pain, sleep disorders, cancer-related cognitive impairment, emotional stress, symptoms of depression and anxiety, problems with relationships, reduced sexual identity, fertility problems, and fear of cancer relapse [ 13 , 14 ]. Furthermore, patients with hormone therapy suffer hot flashes, sweats, joint pain, weight gain, decreased libido, and low energy [ 52 ]. A sizeable number of these women also experience changes in employment status which can happen even 5–10 years following diagnosis [ 15 ]. Given that all these changes alter the structure of the woman’s everyday life, personalized care and treatment plans in cancer survivors are highlighted in the literature with extended specialized support being proposed that enables them to make a better psychosocially adjusted transition from treatment to follow-up [ 53 ] and advocating for the patient’s participation in all decisions that affect her during this period [ 54 ]. Further research is needed concerning how to structure the follow-up and support offered to these women during this stage so as to meet their needs and help them adjust to their new reality with the chronic sequelae caused by cancer and its treatment. On the other hand, the personal transformation of the initial stages of the journey are best seen during this phase. The literature shows that women who have had breast cancer report changes in their philosophy of life, such as embarking on a new life path, changing their priorities in life, as well as valuing life in general [ 42 ]. Most of the participants in our study place special emphasis on appreciating life, enjoying it more, and living each day to the fullest. Cancer survivors report being aware of how precarious life is, while also feeling the joy of being alive [ 55 ]. Similarly, they have been found to be more resilient and better able to repair their mood than healthy women [ 56 ].

About 5% of all patients with breast cancer are diagnosed when the disease is metastatic, whereas some 30% have suffered a relapse of an early breast cancer [ 17 ]. We saw that some women suffering a relapse after initial treatment with curative intent tend to wonder if the treatment was sufficient or if they should have done something more to prevent the relapse. Metastatic breast cancer is uncurable, which is why these women’s main psychosocial challenges are not the same as those who are diagnosed in early stages [ 18 ]. Faced with incurability, the women react with shock and fear of imminent death, but this anxiety diminishes once they begin treatment and learn that there are more treatment options [ 17 ]. During this phase, the interviewees reported impaired physical QoL and functioning, being hindered by pain, fatigue, or menopausal symptoms. Emotionally, they report suffering bouts of depression and anxiety, as well as fear because of the spread of their cancer. As for their relational QoL, their children’s welfare is their number one concern, especially for mothers of young children [ 17 , 57 ]. What’s more, these women felt isolated from society in general and, more specifically, from the non-advanced breast cancer community, inasmuch as they feel that nobody understands what they are going through [ 18 ]. A psychosocial approach is especially important in this phase to help these women to continuously adapt to the changes of their individual clinical situation and to the progression of the disease, thereby improving their coping.

Clinical implications

Having first-person information enables us to comprehend in detail the experiences of breast cancer patients, their situation, and emotional state, which favors holistic cancer care for health professionals.

Healthcare professionals should prepare women for a changed life situation, as well as to face prolonged, multimodal treatment (surgery, chemotherapy, hormone therapy, radiotherapy), and to confront physical and psychological sequelae, as well as the fear surrounding an uncertain prognosis. It is important to help them manage their expectations and fears and, to identify and address the issues and concerns that arise at different time points during treatment. The information and support offered should be adjusted to each woman’s individual needs, her life situation, her coping style, and the time and stage of their cancer. This more empathic, understanding outlook can also contribute to improving the physician-patient rapport, promoting communication, understanding, and shared decision-making.

Finally, a comprehensive understanding of the women’s psychosocial support endorses their belonging to groups of women with breast cancer, in which there is a relationship among equals. Further research is needed to specify the type needed so as to decrease both the impact of the death of women in the group, as well as the vast amount of information that they may end up obtaining, without needing it or requesting it.

Limitations

This study was performed with Spanish participants, which is why certain aspects cannot reflect the experiences of breast cancer patients from other countries, given the particularities of both the Spanish healthcare system and Spanish culture. Likewise, the data attained were specific to women with breast cancer, which can scarcely be extrapolated to individuals with other cancers. Moreover, the findings do not reflect men’s experiences with breast cancer and research with this group would enrich the field further. In addition, the age of our participants ranged from 34 to 61 years; hence the results should be interpreted for a middle-aged population and do not reflect the experiences of women diagnosed at very early or very old ages. Finally, we believe that there may be a bias regarding the women who agree to participate, as this group has probably accepted their condition more, as well as having worked on it more.

Despite these limitations, we hope that our findings can contribute to better understanding the experiences of women with breast cancer.

Acknowledgments

The authors are grateful to the investigators of the Neoetic study and the Bioetic Group of the Spanish Society of Medical Oncology (SEOM) for their contribution to this study. We would like to thank all the women who generously shared their experiences with us, the support of HealthyOnco ( www.healthyonco.com ), and Priscilla Chase Duran for editing and translating the manuscript.

Funding Statement

This work was funded by the Spanish Society of Medical Oncology (SEOM) in 2018. The sponsor of this research has not participated in the design of research, in writing the report, or in the decision to submit the article for publication.

Data Availability

• Open access
• Published: 13 August 2024

Knowledge, skills, and confidence gaps impacting treatment decision making in relapsed/refractory chronic lymphocytic leukemia and mantle cell lymphoma: a quantitative survey study in France, Germany, and the United States

• Sophie Peloquin 1   na1 ,
• Florence Cymbalista 2   na1 ,
• Martin Dreyling 3   na1 ,
• Nirav N. Shah 4   na1 ,
• Suzanne Murray 1 ,
• Romano Del Fiacco 5 ,
• Catherine E. Muehlenbein 6 &
• Patrice Lazure 1  

BMC Cancer volume  24 , Article number:  1003 ( 2024 ) Cite this article

Metrics details

With recent advancements in the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), healthcare specialists may face challenges making treatment and management decisions based on latest evidence for the optimal care of patients with these conditions. This study aimed to identify specific knowledge, skills, and confidence gaps impacting the treatment of CLL and MCL, to inform future educational activities.

Hematologists and hemato-oncologists (HCPs, n  = 224) from France (academic settings), Germany, and the United States (academic and community settings) responded to a 15-minute quantitative needs assessment survey that measured perceived knowledge, skills, and confidence levels regarding different aspects of treatment and management of CLL and MCL patients, as well as clinical case questions. Descriptive statistics (cross tabulations) and Chi-square tests were conducted.

Four areas of educational need were identified: (1) sub-optimal knowledge of treatment guidelines; (2) sub-optimal knowledge of molecular testing to inform CLL/MCL treatment decisions; (3) sub-optimal skills when making treatment decisions according to patient profile (co-morbidities, molecular testing results); and (4) challenges balancing the risk of toxicities with benefits of treatment. Over one-third of the respondents reported skill gaps when selecting suitable treatment options and prescribing therapies and reported a lack in confidence to initiate and manage treatment. Larger gaps in knowledge of guidelines and skills in patient assessment were identified in MCL, compared to CLL.

Conclusions

This study suggests the need for continuing medical education specifically to improve knowledge of treatment guidelines, and to assist clinicians in developing skills and confidence when faced with clinical decision-making scenarios of patients with specific comorbidities and/or molecular test results, for example, through case-based learning activities.

Peer Review reports

Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are two relatively rare conditions that although distinct, share some biological, epidemiological, and clinical features [ 1 ]. The clinical progression of both hematological malignancies vary, as some tumors are indolent, while others behave aggressively. Understanding the mechanisms underlying disease heterogeneity is increasingly relevant due to the ability to target high risk mutations with novel therapeutics [ 1 ]. It is recommended that mutation status of tumor protein p53 (TP53) and the immunoglobulin heavy-chain variable region gene (IGHV) is determined in order to guide treatment of patients with CLL [ 2 ] and MCL [ 3 ].

The treatment landscape for patients with CLL and MCL has significantly changed with the approval of oral targeted therapies such as B-cell lymphoma 2 (BCL-2) inhibitors, and Bruton’s tyrosine kinase (BTK) inhibitors [ 4 , 5 , 6 ]. Knowledge of best practices in incorporating and sequencing novel therapies and utilizing risk-adapted treatment approaches are crucial for improved outcomes in the treatment of CLL and MCL [ 7 ]. Decisions on the optimal treatment should take into account a patient’s prior therapy, remission duration, and preferences. Integrating all of these complex factors when managing relapses can be challenging, especially in the context of time-limited outpatient consultations.

Covalent BTK inhibitors such as ibrutinib have had an important impact on the management of both CLL and MCL with high efficacy and favorable tolerability even in heavily treated patients [ 8 ]. BCL2 inhibitors and BTK inhibitors have improved outcomes for patients with CLL, including patients with genetic mutations or unmutated IGHV [ 9 , 10 ]. While these agents are now standard of care in both CLL and MCL, relapse is inevitable [ 8 , 11 ]. In addition, the combined use of BTK and BCL2 inhibitors is still investigational [ 12 ] and is associated with certain cardiovascular and gastrointestinal toxicities (both CLL and MCL) [ 13 ] and with hematological complications (CLL) [ 14 ] making long-term usage challenging.

Patients with CLL disease progression after BTK inhibitors and BCL2 inhibitors are generally high-risk patients with poor outcomes, and an approach to monitoring and management should account for their specific clinical needs. New options for this double refractory group now include targeting BTK through a different mechanism, such as with non-covalent BTK inhibitors, utilizing cell therapy such as CD19 Chimeric antigen receptor (CAR) T cells, or allogeneic stem cell transplant which remains an option in certain patient scenarios [ 8 , 15 , 16 , 17 , 18 ].

Though the treatment of MCL has similarly evolved with incorporation of rituximab and high dose cytarabine based induction regimens along with BTK inhibitors, these approaches are associated with short and long-term toxicity [ 7 ]. Incorporating targeted therapies, such as BTK inhibitors, into frontline therapy is being investigated as a way to increase response durability, offer more tolerable combination therapy options, and limit use of procedures such as a consolidative autologous stem cell transplant [ 19 , 20 ]. For patients with relapsed or refractory MCL or CLL, it is recommended that providers discuss advanced treatment options with them, and engage them in treatment decisions as well as care and symptom management for their condition [ 21 ].

Treating relapsed/refractory CLL and MCL requires complex decision making and patient input at different stages of treatment. Therefore, patient education about their therapies by providers is crucial. Both oncologists and hematologists play a critical role in making decisions on molecular testing and treatment, and it is essential that they engage and educate patients on the complicated factors associated with their care [ 13 , 22 , 23 ].

The rapidly evolving treatment landscape described above may create challenges for hemato-oncologists and hematologists (HOs/HMs hereafter). To the authors’ knowledge, there has been limited research conducted to understand the specific educational needs of the healthcare providers (HCPs) that provide care to patients with relapsing or refractory disease in CLL or MCL. It is important to identify these challenges, to inform future continuing education initiatives aimed to adequately support HOs/HMs. This study aims to identify the education needs of HOs/HMs in the treatment and management of patients with relapsed-refractory CLL or MCL. This study aimed to assess the knowledge, skill, confidence levels, and gaps reported by HOs/HMs in addition to attitudinal, systemic, and contextual challenges which may interfere with the application of latest knowledge in practice in France, Germany, and United States.

Overall approach

A survey-based, quantitative needs assessment approach [ 24 ] was used to identify the educational needs (in the form of current knowledge, skills, and confidence gaps) of HOs/HMs in relation to the treatment and management of patients with relapse-refractory CLL or MCL. The study design and initial tool development were informed by well-established frameworks in the development of evidence-based continuing medical education [ 25 , 26 ], a review of current literature (including findings from an unpublished qualitative report on clinical challenges in this area), guidelines, and discussions between educational experts (co-authors SP, PL) and clinical experts (co-authors FC, MD, NS). All components of this study were approved by an international independent ethical review board (Veritas IRB, Canada, Tracking Number 2021-2930-9264-1), and all participants agreed to informed consent forms describing the nature and confidentiality of their participation, as well as their rights as a participant. All surveys were completed online.

Survey design

The data collection tool comprised of an initial screening to ensure eligibility according to the inclusion criteria described above, and a survey. The survey items were grouped into three sections that inquired about CLL only, MCL only, and CLL and MCL together. The first two disease-specific sections included self-report questions to measure respondents’ knowledge and skill levels, (using a 5-point Likert-type scale, from 1-none to 5- expert), confidence level (5-point scale, from 1-not at all to 5-very confident), agreement (6-point Likert-like scale, from 1-strongly disagree to 6-strongly agree), and the frequency of specific practices related to CLL or MCL care (5-point scale, from 1-never to 5-always). Survey respondents were presented with disease-specific case scenarios and asked to select the most appropriate option among the nominal response choices presented, and to provide a short justification of their response, to objectively measure knowledge and skills when using molecular tests to guide treatment selection, initiation, and sequencing in relation to current guidelines and best practices. The last section included questions of self-reported confidence, frequency of specific practices and agreements, using the same scales as the first two sections. These questions focused on items unlikely to vary based on the specific disease, such as patient education, management of patient adherence, or perceptions and processes for integration of novel therapies into practice.

The data collection tool was developed in English and translated into French and German so all targeted respondents could participate in their local language. After programming, beta-testing was performed by researchers to verify the quality and functionality of the online survey as intended. The survey was strategically designed to ask relevant questions based on the respondent’s expected knowledge and skills. For example, USA respondents were asked about NCCN guidelines [ 27 , 28 ], while European respondents were asked about European Society for Medical Oncology (ESMO)/European Hematology Association (EHA) [ 29 , 30 , 31 ].

Participants

To be eligible, respondents were required to have: (1) 50% or more of their professional time dedicated to direct patient care (i.e., not solely in research, teaching or in an administrative role); (2) over two years of post-residency experience in hematology or hemato-oncology; (3) a minimum of five CLL and two MCL patients treated in the past year; and (4) prescribed a BTK inhibitor for the treatment of CLL or MCL. In addition, France community settings were not included as these settings were thought by the authors to seldom treat patients with relapsed CLL and MCL. Exclusion was made on the basis of participants not meeting inclusion criteria or quotas for purposive sampling already being full.

Purposive sampling [ 32 ] was employed to ensure inclusion of professionals who are most involved in the care of patients with CLL and MCL, and who would therefore be the intended audience of future educational activities that this study seeks to inform. This approach aimed to obtain a balanced distribution of participants across countries and practice settings. Setting was categorized as either academic (including university-affiliated hospitals) or community (private clinics, public non-academic hospitals, solo-practice clinics, community clinics).

Data collection

Participants were recruited based on their profession and specialty, from a panel of potentially eligible respondents registered to receive invitations for research studies operating in accordance with the guidelines of the ICC/ESOMAR International Code on Market, Opinion and Social Research and Data Analytics [ 33 ]. Email invitations included a secure link to a screener to ensure interested respondents met the inclusion criteria. Eligible respondents were provided with a consent form then directed to the online survey.

Data collection occurred between March 16 and April 29, 2022. Participants received compensation according to their country of practice and profession or specialty. As with all study components, compensation was IRB approved in accordance with international ethical guidelines for equity, transparency, and integrity.

Responses to knowledge and skill items were regrouped into two categories for analysis, out of 5 options: 1 = none, 2 = basic, or 3 = intermediate were labelled “sub-optimal” and 4 = advanced, 5 = expert were re-coded as “optimal”. Responses to the 6-point Likert scale for agreement items were regrouped into four categories: “disagree or strongly disagree,” “slightly disagree,” “slightly agree”, and “agree or strongly agree.” The 5-point confidence scale was regrouped as: “sub-optimal” (1 = not, 2 = slightly, 3 = somewhat) and “optimal” (4 = confident, 5 = very confident). Descriptive statistics such as cross-tabulations were applied for the data analysis using SPSS 27.0 software (IBM Corporation, Armonk, NY, USA). Analysis focused on five sub-groups, based on country and practice setting: France academic, Germany academic, Germany community, USA academic, and USA community. Sub-group analysis by years of practice is also reported, comparing respondents with 2–10, 11–20 and 21 years or more of practice. Findings reported here focus on areas that showed important gaps, with the aim of informing future education.

Demographics and clinical characteristics

Results are based on data from 224 eligible survey participants. The median number of patients with CLL and MCL treated by the respondents of the last two years was 90 and 40, respectively. Table  1 details sample demographics and clinical characteristics.

Main findings

Five key areas of educational needs amongst HOs/HMs were found: (1) knowledge of treatment guidelines; (2) knowledge of molecular testing to inform CLL/MCL treatment decisions; (3) skills when making treatment decisions according to patient profile (comorbidities, molecular testing); (4) challenges balancing the risk of toxicities with benefits of treatment; and (5) challenges related to patient-provider communication and shared decision making. This article will focus on the first four findings, as the fifth one has been described previously [ 34 ].

Knowledge of treatment guidelines

In relation to CLL, higher knowledge gaps about latest guidelines were identified from the community settings in Germany, with 70% reporting sub-optimal knowledge levels of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL). In France, most respondents were knowledgeable of the national guidelines for CLL, however over 34% of participants had a knowledge gap of all other international or European guidelines referenced. In the USA, those in community settings reported sub-optimal knowledge levels of NCCN CLL (36%) guidelines (see Table  2 ). When respondents were asked what the next steps would be if they suspected CLL disease progression in a case scenario of an older patient progressing on ibrutinib, 21% of respondents selected to start treatment while 79% opted to first order molecular or cytogenic testing. Community-based respondents in Germany (33%) were more likely to start treatment (See Fig.  1 ). When asked more specifically about their next treatment, 50% selected to start the patient on venetoclax, while 35% selected to start the patient on a second generation BTK inhibitor, such as acalabrutinib.

Response to a CLL case scenario

In relation to MCL, higher knowledge gaps were also identified from the German community settings, with 69% reporting sub-optimal knowledge levels of the EHA ESMO guidelines for MCL. Slightly over half (51%) of participants for France Academic settings reported sub-optimal knowledge levels of these guidelines. Nearly a third of respondents (32%) were sub-optimally knowledgeable of their national guidelines for MCL. In the USA, those in community settings reported sub-optimal knowledge levels of NCCN MCL (38%) guidelines (see Table  2 ).

No significant differences in years of practice were observed regarding knowledge of the guidelines, or for the case presented above.

Molecular tests to inform CLL/MCL decision making

When asked which molecular tests are most important to plan treatment for patients with refractory/relapse CLL, while del 17p was selected by 87% of respondents and detection of TP53 mutation by 84%, only 57% reported IGHV as important. The molecular test that was the least frequently selected by respondents as important to plan treatment for CLL was presence of Phospholipase C Gamma 2 ( PLCG2) mutation (21%) (see Table  3 ).

When asked the same question to plan treatment for patients with refractory/relapse MCL, del 17p was also the most often selected by 74% of respondents, followed by detection of TP53 mutation (73%). The molecular test that was the least frequently selected was again presence of PLCG2 mutation (19%) (see Table  3 ).

Knowledge of the impact of molecular test results on CLL treatment planning was reported at sub-optimal levels for a PLCG2 mutation (66% of respondents). This was followed by BTK mutation (39%), with a significant difference between years of practice (2–10 years 52%, 11–20 years 60%, 21 + years 74%, p  = 0.032). Other knowledge gaps were reported, in a lesser proportion, for the del 17p (30%; 2–10 years 41%, 11–20 years 30%, 21 + years 20%, p  = 0.048) and TP53 mutations (31%; 2–10 years 45%, 11–20 years 31%, 21 + years 18%, p  = 0.005). Table  3 provides details per country and practice setting.

When considering treatment planning for MCL, knowledge was reported at sub-optimal levels for a PLCG2 mutation (59% of respondents). This was followed by IGHV mutation status for MCL (sub-optimal knowledge 54% compared to CLL: 7%) and BTK mutation (48%; 2–10 years 65%, 11–20 years 44%, 21 + years 39%, p  = 0.008). Other knowledge gaps were reported, in a lesser proportion, for the del 17p mutation (43%; 2–10 years 62%, 11–20 years 37%, 21 + years 33%, p  = 0.001) and the TP53 mutation (41%; 2–10 years 59%, 11–20 years 34%, 21 + years 33%, p  = 0.003), except in community settings in Germany, where the gaps remained high for both mutations (del 17p: 56%) and (TP53: 59%) (see Table  3 ).

Skills when making treatment decisions according to patient profile (comorbidities, molecular testing)

In relation to CLL, over a quarter of participants (27%; 2–10 years 39%, 11–20 years 27%, 21 + years 17%, p  = 0.025) reported their skills at sub-optimal levels when assessing which patients needed molecular tests. Nearly one third reported sub-optimal skill levels making treatment decisions based on those tests (32%; 2–10 years 48%, 11–20 years 29%, 21 + years 22%, p  = 0.005; see Table  4 ). 35% of respondents reported skill gaps in treatment decision making with patients with CLL who have many comorbidities (Germany, community, 40%; USA academic, 30%, community, 32%; see Table  4 ) (2–10 years 45%, 11–20 years 26%, 21 + years 22%, p  = 0.008).

In relation to MCL, over a third of participants reported their skills at sub-optimal levels when assessing which patients needed molecular tests (34%) or when making treatment decisions based on those tests (37%; see Table  4 ). No significant difference between experience sub-groups were observed.

Regarding sequencing second line therapy for CLL, fewer skill gaps were reported in the academic setting of Germany (14%, vs. 34% in total sample, Table  5 ), and in more experienced participants (2–10 years 49%, 11–20 years 32%, 21 + years 22%, p  = 0.006). However, 40% of all respondents reported sub-optimal skill levels when selecting next line of treatment for CLL after discontinuing BCL-2 inhibitors (2–10 years 54%, 11–20 years 35%, 21 + years 33%, p  = 0.025). Respondents reported skill gaps when selecting next line of treatment after discontinuing BTK inhibitors (33%), with elevated levels in in Germany’s community setting (40%, in contrast to the academic settings in the USA where only 29% reported a skill gap in this area; Table  5 ) and differences between experience sub-groups (2–10 years 46%, 11–20 years 30%, 21 + years 27%, p  = 0.043). This.

Similar skill gaps were reported when considering MCL, with lower frequency of sub-optimal levels in the academic setting of Germany for sequencing second line therapy (23%, vs. 32 for overall sample; Table  5 ). Differences by experience sub-group were observed (2–10 years 45%, 11–20 years 31%, 21 + years 20%, p  = 0.012). Respondents reported skill gaps when selecting next line of treatment for MCL after discontinuing BTK inhibitors (39%; no significant difference by experience), with higher levels in in Germany’s community setting (53%) followed by the academic setting in France (47%).

A skill gap in sequencing treatment in patients on anti-coagulation medication with a bleeding disorder, or with cardiac risk factors was found amongst over a third of respondents (both CLL and MCL) mainly in the academic setting of France (42%). The respondents in academic settings in Germany (18%) reported a relatively low level of skill gaps when sequencing treatment in patients with such conditions. No difference by experience was observed.

Challenges balancing the risk of toxicities with benefits of treatment

When considering CLL, 42% of participants slightly agreed that “certain BTK inhibitors have a reduced risk for cardiac toxicity” (Fig.  2 ), while another 42% agreed or strongly agreed. Elevated percentages of strong to light disagreement were observed in Germany’s community setting (20%) and France’s academic setting (21%), while more experienced participants agreed or strongly agreed with the statement in a higher proportion (2–10 years 35%, 11–20 years 38%, 21 + years 53%, p  = 0.026).

When considering MCL, similarly, the majority of respondents (76%) strongly to slightly agreed with that statement, with elevated numbers of disagreement in Germany’s community setting (27%) (Fig. 2), and more experienced participants more frequently agreed or strongly agreed with the statement (2–10 years 26%, 11–20 years 35%, 21 + years 45%, p  = 0.038).

Back to CLL, the responses from more than one-third (34%) of respondents showed skill gaps weighing risks and benefits of using BTK inhibitors according to CLL patient profile (Table  5 ). This gap was more pronounced in less experienced respondents (2–10 years 51%, 11–20 years 29%, 21 + years 27%, p  = 0.006). In the USA academic setting, 32% reported low confidence when selecting treatment for patients with relapsed/refractory CLL in consideration of potential side effects and toxicities (Table  6 ). When initiating treatment of CLL with acalabrutinib after discontinuing ibrutinib treatment due to intolerance or toxicity, suboptimal confidence level was found among 33% of respondents. No difference by experience was observed for these two confidence gaps.

When considering MCL, 26% of respondents reported low confidence when selecting treatment for patients with relapsed/refractory MCL in consideration of potential side effects and toxicities (Table  6 ; no difference by experience), with elevated sub-optimal levels in the USA academic setting, where 32% reported low confidence.

When asked to consider both CLL and MCL, 30% of respondents had a confidence gap avoiding cumulative toxicities when initiating treatment with new agents, and lower confidence levels were reported when selecting treatment in consideration of potential side effects and toxicities for MCL compared to CLL. (see Table  6 ; no difference by experience).

% Agree / Disagree: “Certain BTK inhibitors have reduced risk for cardiac toxicity”

This study assessed the current educational needs for HCPs involved in CLL and/or MCL, identifying specific knowledge, skills, and confidence gaps in the treatment of patients with relapsed/refractory CLL or MCL. The findings indicate a need to improve, in both disease conditions, use of current guidelines, knowledge of molecular tests to guide treatment decisions, and the skills to select the right treatment according to the patient profile of comorbidities and molecular test results. In addition, efforts should be made to increase HCP’s confidence when faced with complex patient needs.

Knowledge of guidelines was lower in community settings, especially when treating MCL, which is not surprising given the rarity of this disease, even compared to CLL, and complex cases are typically referred to academic centers. Certain gaps were anticipated due to regional variation in access, setting and standard of care [ 35 ], however the lack of familiarity with current standards of care may limit possible treatment options offered to patients, prioritizing agents HCPs are most familiar with, which can contribute to inconsistencies in patient care depending on the treating HCP [ 36 ]. The fact that over a third of HCPs would sequence acalabrutinib after progression on ibrutinib (see second question of case scenario) is not aligned with the recommendations of guidelines [ 27 , 30 , 31 ], and demonstrate an important need for education.

BTK mutation testing is relatively new, particularly in Europe, which may necessitate education to enhance understanding on when it may be appropriate [ 19 ]. The clinical utility of PLCG2 is currently limited [ 37 ] but considering practice trends, it may have increased utility in the future [ 38 ]. In anticipation of emerging needs, early continuing education for oncologists and hematologists should be planned and developed. Furthermore, this study confirms that del p17, TP53, and IGHV are currently the most frequently used tests for treatment decision making [ 39 ]. However, it remains surprising that even these tests were not ordered with greater fidelity, especially with IGHV which was only deemed to be important by 57% of providers. This might be attributed to the shifting treatment landscape. IGHV mutation status, while providing useful prognostic information, is only essential when considering chemoimmunotherapy as a treatment option and in recent years, more targeted approaches have surpassed chemoimmunotherapy among the preferred treatment options [ 40 ]. This suggests that educational efforts should seek to focus on improving knowledge of these molecular tests.

This study observed that when a given molecular test was perceived as less relevant in treatment decision making, the HCP’s level of knowledge of it was low. Increasing awareness of current and potential relevance of a test may encourage HCPs to improve their knowledge and familiarity broadening their repertoire of valuable treatment options to address the observed challenges in treatment selection, especially in complex cases. Similarly, access to different molecules in the treatment of patients with CLL or MCL (e.g., BTK inhibitors, BCL2 inhibitors) may have influenced the level of importance at which they were perceived, which in turn would influence the HCP’s reported levels of knowledge and skills. Even when molecules were approved around the same time in the three countries, official reimbursement processes may differ, which ultimately impact access.

Shanbhag (2021) [ 41 ] has described concerns about the side effects of therapeutic advancements in the treatment landscape of CLL. Although such advancements have improved treatment tolerability, they have not completely mitigated the risk of cardiac toxicity. This study found skill gaps when selecting treatment that avoids those risks posed by potential toxicities. Likewise, skill gaps were also identified regarding HCPs’ selection of treatment for patients with cardiac risk factors and other comorbidities, or those with a full treatment history and a need for novel therapies. This suggests management of patients with complex profiles should be a priority of future educational efforts, based on emerging evidence for best practices. Recent studies have shown that interactive problem-based continuing medical education (CME) using case studies [ 42 ], and online certified CME activities [ 43 ] relevant to the HCP’s practice needs, can improve skills.

As we found relatively smaller gaps when HCPs are based in academic settings, a greater focus should be placed on offering education on this topic for those in community settings, especially for HCPs treating more patients with relapsed MCL. This study pointed to country and setting variations that should be considered when designing relevant educational initiatives, but some more local differences may exist. For example, though our results show that overall, German HCPs in academic settings show less need for continuing education on selecting 2nd line treatments, there could be value in a closer examination to quantify needs in specific settings, to inform local initiatives. Pre-test evaluations prior to education sessions may help focus the conversation on areas of deficiencies, rather than a one-size fits all approach to instruction.

In both CLL and MCL, for most of the items that showed a difference in years of practice, the gaps were higher among respondents with the least amount of experience. To be the most effective, medical education solutions should target community oncologists early in their practice, while still including more experienced practitioners, given that in most cases, the percentage of these experienced practitioners having knowledge or skill gaps was still sufficiently high enough to warrant medical education.

Our findings suggest that future education should build core knowledge and appreciation of the established clinical relevance of molecular tests, support standard algorithms for clinical management with a goal to improve provider confidence in the management of complex malignancies like CLL and MCL. This could involve peer-guided hands-on training, combined with more traditional knowledge building efforts in the form of lectures and journal clubs within the hematology and oncology departments.

Limitations

Most survey items asked participants to self-assess their current knowledge and competencies according to what is expected of them in their professional role, and hence reflects individual perceptions, rather than objective and validated assessments by a third-party evaluator. Thorough and objective knowledge and competency-based assessments may be possible in the scope of an in-depth course lasting multiple weeks, but is highly difficult to achieve in the scope of a research-based needs assessment, that utilizes reasonable methods (i.e., 15-minute online survey) to attract sufficient interest. To address this limitation, a few case studies were included in the survey to gather a more objective assessment of respondents’ clinical decision-making and applied knowledge of best practices. In addition, the quantitative nature of the study limits the nuances in responses that would best reflect the actual knowledge, judgment, or belief of a respondent. These issues were mitigated in part by the inclusion of open answer options for some, though not all items, to ensure the survey length is within its stated duration. While the survey was critically reviewed by both educational and clinical experts collaborating on this project to verify full and consistent comprehension of survey questions and items, the divergence in individual interpretation of survey questions by the respondents themselves was not assessed. The validity of few findings could be questioned, as was the case for the reported caseload of MCL and CLL patients; numbers were higher than expected, which suggests that facility, rather than individual, numbers were reported (see Table  1 , range and median values). This did not impact the conclusions of the study, as patient caseload was not a core variable in the final analysis. However, as in any evidence-base generation, validation of findings could be strengthened by other research groups conducting similar initiatives using complementary methods (e.g., interviews, third-party observations). Unfortunately, to co-authors knowledge, these types of studies are currently missing on the topic of educational needs for HCPs treating MCL and/or CLL. Sample size by country was small and may not be a comprehensive representation of the experience of all HCPs who treat CLL and MCL in each country. Data should be interpreted as an identification of trends, which can provide relevant indicators for educators planning and developing continuing education activities [ 25 , 26 ], but should not replace local validation of the challenges when appropriate.

Implications

The findings of this study have implications for clinical practice and CME, continuing professional development, and performance improvement / quality improvement initiatives for CLL and/or MCL treatment decision making. The results can be applied in the design of curriculum for HCP workplace training, for example in the management of cardiac toxicity with covalent BTK inhibitors [ 35 , 36 ]. Novel educational approaches for HOs/HMs have shown significant impact on knowledge, competence and confidence – a recent interactive CME program in CLL used educational videos and in-person facilitation along with assessment with positive results [ 43 ]. Our study and others suggest that incorporating educational initiatives in a real-world setting (clinical practice) can demonstrate the relevance and broad impact of addressing practice gaps, while maximizing the capacity of the setting and the care they provide.

Overall, there is a need for additional research to better understand the factors explaining gaps observed in this study. Further empirical research on the effectiveness and factors that support utilization of CLL and MCL guidelines in practice would be necessary. Research to understand barriers that HCPs face when trying to engage patients in treatment planning and when adopting the latest tests or practices for CLL and/or MCL would enrich these efforts. Similarly, qualitative research could also complement and add depth and insight into any of the issues mentioned.

As new treatments emerge, and overall survival increases, HCPs in this field will have access to a broadening arsenal of treatment to choose from. Continuing professional development programs must stay current with the educational needs resulting from these scientific and clinical advancements and consistently aim to support HCPs in acquiring and further developing relevant knowledge, skills and confidence. Findings from this study can be leveraged by curriculum developers and education providers to develop tailored educational programs that meet the needs of oncology professionals caring for patients with relapsed or refractory CLL or MCL.

Data availability

Aggregated and anonymized data used and/or analysed in the current study will be made available to the editors of the journal for review or query upon reasonable request to the corresponding author.

Abbreviations

chronic lymphocytic leukemia

mantle cell lymphoma

tumor protein p53

Immunoglobulin heavy-chain variable region gene

B-cell lymphoma 2

Bruton’s tyrosine kinase

chimeric antigen receptor

National Comprehensive Cancer Network

European Hematology Association

European Society for Medical Oncology

the International Workshop on Chronic Lymphocytic Leukemia

hemato-oncologists/hematologists

Healthcare Providers

Independent review board

Phospholipase C Gamma 2

Continuing Medical Education

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Acknowledgements

The authors would like to acknowledge the support provided by Monica Augustyniak (senior researcher, AXDEV Group) and Lu Fan (researcher, AXDEV Group) who supported the development of this manuscript, as well as Randa Dalle (senior project manager, AXDEV Group) who supported communications, project planning and coordination of data collection. The authors would also like to thank all the participants who took part in this study.

This study was financially supported by educational research funds from Eli Lilly & Company to AXDEV Global Inc. A representative of the funder’s medical education department (co-author RDF) contributed to the initial conceptualization of the study, the interpretation of aggregated data, and critically reviewed the draft of this article. The funder had no role in the data collection and analysis of the data.

Author information

Florence Cymbalista, Martin Dreyling and Nirav N. Shah contributed equally to this work.

Authors and Affiliations

AXDEV Group Inc, Brossard, QC, Canada

Sophie Peloquin, Suzanne Murray & Patrice Lazure

Université Sorbonne Paris Nord, Bobigny, France

Florence Cymbalista

Ludwig-Maximilian-University Hospital Munich, Munich, Germany

Martin Dreyling

Medical College of Wisconsin, Milwaukee, WI, USA

Nirav N. Shah

Eli Lilly and Company, Florence, Toscana, Italy

Romano Del Fiacco

Eli Lilly and Company, Indianapolis, IN, USA

Catherine E. Muehlenbein

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Contributions

SP, SM, and RDF contributed to project conceptualization and funding acquisition. SP, PL, and SM designed the study. PL led the development of data collection tools, monitoring of data collection, and analysis of quantitative data. FC, MD, and NS formed a steering committee of clinical subject matter experts who contributed to the refinement of the study design and tools. All authors contributed to the interpretation of the findings. SP and PL directly supervised development of the original draft of the manuscript, which was critically reviewed by FC, MD, NS, RDF, CEM, and SM for important intellectual content. All authors have approved of the final version of the manuscript and have agreed to be accountable for all aspects of the work.

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Correspondence to Sophie Peloquin .

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Ethics approval and consent to participate.

All components of this study were approved by an international independent ethical review board (Veritas IRB, Canada, Tracking Number 2021-2930-9264-1), and all participants agreed to informed consent forms describing the nature and confidentiality of their participation, as well as their rights as a participant.

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Competing interests

SP and PL are employees of AXDEV Group Inc. SM is CEO & founder of AXDEV Group Inc., AXDEV Global Inc., and AXDEV Europe GmbH. NS reports participation on advisory boards and/or consultancy for Kite Pharma, BMS-Juno, TG therapeutics, Miltenyi Biotec, Lilly-LOXO, Epizyme, Incyte, Novartis, Janssen, Seattle Genetics, and Umoja; and research funding and honoraria from Miltenyi Biotec.FC reports participation on advisory boards and/or consultancy for AbbVie, Lilly, Janssen, Astra Zeneca.MD reports participation on advisory boards for Astra Zeneca, Beigene, BMS/Celgene, Gilead/Kite, Janssen, Lilly/Loxo, Novartis, Roche. He has research funding from Abbvie, Bayer, BMS/Celgene, Gilead/Kite, Janssen, Roche, and honoraria from Astra Zeneca, Beigene, Gilead/Kite, Janssen, Lilly, Novartis, Roche. MD is an associate editor for HemaSphere. NS, FC, and MD received research honoraria from AXDEV Global for their contribution to the study design, review of research tools, and interpretation of the findings from this study. RDF and CEM are employees of Eli Lilly and Company.

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Peloquin, S., Cymbalista, F., Dreyling, M. et al. Knowledge, skills, and confidence gaps impacting treatment decision making in relapsed/refractory chronic lymphocytic leukemia and mantle cell lymphoma: a quantitative survey study in France, Germany, and the United States. BMC Cancer 24 , 1003 (2024). https://doi.org/10.1186/s12885-024-12745-1

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DOI : https://doi.org/10.1186/s12885-024-12745-1

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• Chronic lymphocytic leukemia (CLL)
• Mantle cell lymphoma (MCL)
• Treatment decisions
• Continuing medical education
• Continuing professional development
• Needs assessment

ISSN: 1471-2407

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