12 January 2021

12 January 2021

The National Cancer Institute (NCI) recently announced that they will start tracking breast cancer recurrence. Currently, initial cases of breast cancer are reported, but local / regional (in the breast or underarm lymph nodes) or metastatic (elsewhere in the body, most commonly lungs, liver bones and brain) breast cancer recurrences are not. It is unclear how many patients with early stage breast cancer experience a recurrence, although it has been reported to be approximately 30%.

It will be several years before we see meaningful data, but this is most certainly a step in the right direction. Patients and physicians alike are frustrated by the lack of reliable data on recurrence rates. Patients who develop metastatic cancer are frustrated that they are not “counted.” And much credit to Katherine O’Brien, a woman in Chicago who is living with metastatic breast cancer – she led the creation of a change.org petition, which collected nearly 12,000 signatures, requesting that federal and state registries begin collecting this information.

This most certainly is a step in the right direction to ensure that all cases of breast cancer, both initial and recurrent diagnoses, are captured. It’s also a testament to the power of the patient advocate!

Medscape article

17 August 2020

Last year, we asked the online breast cancer community to participate in a survey to assess experiences with endocrine therapy (ET). We are proud to announce that the study has now been published, in the Journal of Cancer Survivorship*.

First of all, I would like to thank all of the participants – we surpassed our accrual goals and this is the largest survey of ET use by patients who participate in online breast cancer communities! 

About the respondents:

  • 111 respondents did not start the recommended ET, and concern about side effects was the primary reason
  • Of those who took ET (2407), 2353 were women and 54 were men
  • Most of the women (74%) were post-menopausal
  • Mean age at diagnosis was 50 for women (range: 23-82) and 54 for men (range: 24-73)
  • Most (87%) were diagnosed at Stage 1-3
  • 100 (4.2%) were diagnosed with de novo Stage 4 / metastatic breast cancer
  • 12% of those diagnosed at an early stage eventually developed Stage 4 / metastatic breast cancer


  • Aromatase inhibitors (AIs) were the most commonly used medication
  • 91% of respondents reported at least one class of side effect that they felt was related to treatment (92% of women and 74% of men)
  • Musculoskeletal and general physical changes (such as weight gain and unhappiness with body image) were the side effects most commonly reported by women
  • Men most commonly reported sexual and cognitive / mood side effects
  • 33% (33% of women and 50% of men) discontinued therapy early
  • 9% reported that they took treatment breaks or discontinued therapy early either without informing their medical team or against their medical team’s advice

Side effect management:

  • 3 classes of side effect management strategies were felt to be most helpful:
    • Healthy diet, exercise, physical therapy
    • Complementary therapy such as yoga, acupuncture and meditation
    • Vitamins, supplements and herbs including medical marijuana 
  • Only 41% of respondents noted any relief from side effect management strategies

Medical team communication: (multiple responses permitted so this category did not add up to 100%)

  • 70% felt supported by their medical team in attempting to discuss side effects
  • 32% were made to feel that they should be better able to handle side effects or that the side effects were not related to treatment
  • 7% did not discuss side effects with their treatment team, feeling that there were more important issues to discuss, that there was not enough time, or they did not feel comfortable

Some other findings:

  • Respondents with early-stage and metastatic breast cancer reported similar side effects and management experiences, even though these two groups of patients have very different supportive needs
  • Men who responded to our survey were less likely to report side effects but more likely to discontinue therapy early compared to women – more information is needed about the experience of men with breast cancer and those taking endocrine therapy

Clearly, there is room for improvement in terms of medical team support and understanding. In addition, as only 41% of respondents noted any relief from side effect management strategies, we need more effective treatments for ET-related side effects. Thank you to all who participated in this survey! We are hopeful that your responses and comments will inspire researchers devote more time to addressing these important issues.

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

16 August 2020

As part of the pathologist’s evaluation of a breast cancer, the presence or absence of the estrogen and progesterone receptor (ER/PR) and level of Her2/neu gene expression is determined. These are important factors used to help guide treatment recommendations for endocrine therapy, chemotherapy, and Her2-targeted therapy. 

If metastatic breast cancer develops (when the primary tumor spreads to other areas of the body, such as the lungs, liver, bone, or brain), it is recommended that ER/PR and Her2/neu testing be performed on the metastatic cancer. It is known that cancers can sometimes mutate and the metastatic lesion may have different characteristics compared with the primary lesion. While current international guidelines do recommend biopsy of the metastatic tumor, this is not always performed.

A study recently published in Breast Cancer Research and Treatment reported on discordance between the primary and metastatic breast cancer. The study was performed in Germany. Among patients treated for breast cancer between 1982 – 2018, 541 had receptor status from both the primary and the metastatic breast cancer documented in the medical record.

The researchers found that there was a 14% discordant rate for ER, a 32% discordant rate for PR, and a 15% discordant rate for Her2/neu. All of these were felt to be clinically meaningful, in that a change in ER/PR or Her2/neu status would result in a change in treatment recommendations. If a tumor loses the ER/PR receptor, endocrine therapy (such as tamoxifen or aromatase inhibitors) would be ineffective. If a tumor gains the Her2 protein, Her2-targeted therapy should be instituted.

They noted several reasons for discordance including:

  • Variability in the testing process, especially as testing procedures have changed over time
  • Tumor heterogeneity – cancers may not be made up of a single cell “clone”
  • Mutation of the tumor over time

Median follow up was 58 months. They noted that loss of ER/PR positivity was associated with worse overall survival, and gain in Her2 positivity was associated with improved overall survival. However, one limitation of the study is that they could not determine if the survival differences were actually due to the changes in the tumor and subsequent treatment. They noted other limitations of the study including that the dataset included patients with Her2 positive disease who were treated prior to the approval of trastuzumab (Herceptin), there were changes in cut-off values for what was considered ER/PR “positive” during the study period, and receptors were not re-checked in a centralized lab.

However, despite the limitations, it is important to note that treatment recommendations could be altered as a result of testing the metastatic cancer. The researchers concluded that “Where feasible, metastatic lesions should be biopsied in accordance with current guidelines.” If you have been diagnosed with metastatic breast cancer, it is important to discuss biopsy of the metastatic tumor with your oncologist, and not assume that it is the same cell type as the primary lesion. This study found that in at least 14% of cases, knowledge of the metastatic tumor biology could alter treatment recommendations.

7 June 2020

An abstract presented at last week’s virtual meeting of the American Society of Clinical Oncology focused on whether or not there is a benefit to surgery for the primary breast tumor in patients with metastatic, or Stage IV, breast cancer.

Metastatic breast cancer (Met-BC) is when the breast cancer spreads beyond the breast and underarm lymph nodes. Common sites of metastases include the lungs, liver, bones, and brain. Anyone diagnosed with breast cancer has the potential to develop metastatic disease, but approximately 5-10% of patients are found to have Met-BC at the time of initial diagnosis, known as de-novo Stage IV. For these patients, it has been controversial whether or not to recommend some form of breast surgery (lumpectomy or mastectomy) to remove the primary tumor. Some studies have shown a survival benefit when the primary tumor is removed, but widespread adoption of the results of these studies has been limited because in many of these studies, patients who underwent surgery were younger, healthier, and had a lower volume of metastatic disease compared with the general population of patients with Met-BC.

Dr. Seema Khan presented the results of the ECOG-ACRIN Research Group E2108 study. In this study, patients who had stable Met-BC (after 4-8 months of treatment) were randomized to either surgery or no surgery for the primary tumor. The two study groups were well-matched for age, race, and breast cancer subtype. With a median follow up of 59 months, there was no improvement in overall survival or in progression-free survival. Local progression (cancer continuing to grow in the breast) was more common in patients who did not undergo surgery (25.6 versus 10.2% at 3 years). At 18-month assessment, health-related quality of life was significantly worse in those who underwent surgery, but no differences were observed at the 6-month or 30-month assessment intervals.

During her presentation, Dr. Khan acknowledged that there may be situations where surgery for the primary tumor is a reasonable option in the setting of Met-BC. She noted that there is room for individualization, but stressed that as there is no survival benefit and no improvement in quality of life, surgery for the primary tumor in the setting of Met-BC should not routinely be performed. 

It is important to note that any medical meeting abstract, whether an oral presentation or poster, has been evaluated by the meeting program committee but has not been subject to rigorous peer review as would occur with a formal manuscript submission. Abstracts often do not include the full set of results, and additional findings may be included in the eventual publication, some of which may be different than those presented in the abstract. We look forward to the peer-reviewed publication when it is available. 

24 April 2020

A new drug was recently approved by the US Food and Drug Administration (FDA) for the treatment of metastatic breast cancer – breast cancer that has spread to other areas of the body, such as the bones, liver, lungs or brain. Sacituzumab govitecan (Trodelvy), which is given by intravenous infusion, was granted accelerated approval to treat metastatic triple negative breast cancer in patients who have already been on 2 prior treatments for their disease. 

Triple negative breast cancer accounts for approximately 15% of breast cancers. It is more common in younger patients, African Americans, and those with a BRCA1 gene mutation. It can be very challenging to treat since there is no specific cellular target, such as the estrogen receptor or Her2/neu protein. Patients with triple-negative breast cancer very commonly receive chemotherapy but the disease may come back or progress despite aggressive treatment.

Sacituzumab govitecan is an antibody-drug conjugate, which is an antibody that is combined with a chemotherapy drug. The antibody targets a protein (trophoblast cell surface antigen-2, or trop-2) on the surface of the cancer cell, and the chemotherapy drug causes breaks in the tumor cell DNA, which leads to cancer cell death. The FDA approval was based on a non-randomized (meaning all patients received the study drug) study of 108 patients who were experiencing disease progression despite receiving between 2 – 10 prior treatment regimens. Among the study participants, approximately 33% experienced a partial or complete tumor response to the medication. Median duration of treatment response was nearly 8 months. Severe adverse reactions included diarrhea, neutropenia (low white blood cell counts), anemia (low red blood cell counts), fatigue, nausea and vomiting. 2 patients stopped treatment due to side effects.

Any advance in the treatment of metastatic breast cancer is welcome news. It is hoped that as new drugs are developed, a longer-lasting response to therapy will be achieved. 

Additional Information:

19 April 2020

The US Food and Drug Administration (FDA) has recently approved a new treatment for patients with metastatic breast cancer. Tucatinib (Tukysa) was approved for use in combination with 2 other agents, trastuzumab (Herceptin) and capecitabine (Xeloda) in patients with unresectable (too advanced to remove with surgery) or metastatic (spread to other areas of the body, such as bone, liver, lungs or brain) Her2/neu over-expressed breast cancer (Her2+). Tucatinib is approved for patients who have already been treated with one or more anti-Her2/neu treatments.

Tucatinib is a an oral (pill) medication known as a tyrosine kinase inhibitor. Results of the Her2CLIMB trial were presented in December at the San Antonio Breast Cancer Symposium. The study enrolled 612 patients with metastatic or unresectable Her2+ breast cancer who had received at least one other Her2+ targeted agent but were experiencing progression of disease. Unique to this study was that almost half of the participants had metastases to the brain – often these patients are excluded from clinical trials.

Some of the key findings were that in patients who received tucatinib with trastuzuab and capecitabine versus those who received trastuzumab and capecitabine alone:

  • Median progression free survival was 7.8 months versus 5.6 moths
  • Median progression free survival for patients with baseline brain metastases was 7.6 versus 5.4 months
  • Median overall survival was 21.9 versus 17.4 months
  • Confirmed objective response rate was 40.6% versus 22.8%

Serious adverse reactions occurred in 26% of patients and 6% of patients had to stop treatment due to adverse reactions. The most common side effects were diarrhea, hand-foot syndrome, nausea, fatigue, liver toxicity, mouth sores, decreased appetite, abdominal pain, headache, anemia and rash.

The approval of tucatinib provides another option for patients with aggressive breast cancer, including those who have brain metastases. However, as previously discussed, this study is a reminder of how far we have to go to achieve a reliable and long-lasting treatment response in patients with metastatic breast cancer.

Additional Information:

4 December 2020

The actress Shannen Doherty revealed today that she has Stage 4 breast cancer. From media reports, it appears that she was initially diagnosed and treated in 2015 and developed a recurrence within the past year.

“Recurrence” simply means that the cancer has come back. Breast cancer can recur in the breast or chest area, which is called a local recurrence. This is usually treated with surgery to remove the recurrent tumor, most commonly mastectomy if lumpectomy was the original operation. Radiation therapy, chemotherapy, or hormonal therapy may also be recommended. The risk of local recurrence after lumpectomy is generally less than 10% and less than 5% after mastectomy.

Breast cancer cells can travel from the breast to the lymph nodes or through the blood stream and then deposit in other organs. This is termed systemic recurrence, metastatic breast cancer, or stage 4 breast cancer. The lungs, liver, bones and brain are the most common sites for metastatic breast cancer. Metastatic breast cancer is not curable, and patients who develop metastatic disease will require lifelong treatment.

Anyone who has been treated for breast cancer can develop metastatic disease. It is estimated that as many as 30% of patients will eventually develop metastatic disease but it difficult to get exact numbers because recurrences are not tracked like initial diagnoses are. The likelihood of developing metastatic disease is higher in patients who are diagnosed at more advanced stages and in those with more aggressive tumor biology / behavior, but even the less aggressive or slower growing tumors have the potential to spread. 

Since the most common sites of spread are the lungs, liver, bones and brain, attention should be paid to changes such as persistent cough or shortness of breath, abdominal pain, increased abdomen size, jaundice (yellowing of the eyes), persistent bone pain, fractures with no history of trauma, severe headaches, and new onset seizure. However, patients may have metastatic disease without any symptoms. While there is no true prevention, endocrine therapy (for those with estrogen receptor positive breast cancer) can reduce risk. A healthy diet, regular exercise, and weight control can also reduce risk. It is of course possible to do “everything right” and still develop metastatic cancer.

As mentioned, treatment for stage 4 breast cancer is lifelong. There have been many advances in the treatment of metastatic breast cancer – chemotherapy is not always required and newer targeted therapies have been developed. This is an area of active research. However, approximately 40,000 women and 500 men will die each year in the US due to metastatic breast cancer. More work is needed to better understand why some patients develop metastatic breast cancer, how to prevent breast cancer from spreading, and how best to treat it once it does spread.

Metastatic breast cancer information from cancer.net
Metastatic Breast Cancer Network
Metastatic Breast Cancer Alliance

25 December 2019

Two studies recently presented at the recent San Antonio Breast Cancer Symposium focused on a subtype of breast cancer known as Her2/neu over-expressed, which include up to 20% of breast cancers. In these tumors, the gene that codes for the Her2 protein receptor has more than the usual number of copies. These tumors tend to have more aggressive growth patterns and up until the development of targeted antibody therapy, prognosis was very poor. 

Targeted antibody therapy including trastuzumab (Herceptin) and pertuzumab (Perjeta) is now standard of care for Her2 breast cancers, even in the setting of early-stage disease. Trastuzumab emtansine (Kadcyla, T-DM1) is an antibody-drug conjugate (ADC, a combination of the antibody and a chemotherapy agent) and is most commonly used in patients with metastatic disease. Unfortunately, not all Her2 tumors respond to therapy, and some tumors that initially respond can mutate and become resistant to therapy. Brain metastases can occur in up to 50% of patients with metastatic Her2 breast cancer, and can be challenging to treat as medications may not be able to pass through the blood-brain barrier to get to the cancer cells. 

Trastuzumab deruxtecan (DS-8201, Enhertu) is an ADC and results of a phase 2 study (DESTINY-Breast01*) were presented. This study included 184 patients with metastatic Her2 breast cancer, who were experiencing disease progression after receiving 2 or more different anti-Her2 treatment protocols (including trastuzumab emtansine, median 6 prior therapies, range 2-27). This was an “open label” study and patients were not randomized. Median follow up was 11 months and findings included:

  • Median treatment duration was 10 months
  • Overall response rate was 60.3% (at least 2 follow up scans, 6 weeks apart)
  • 11 patients (6%) experienced a complete response (apparent resolution of disease)
  • 101 patients (55%) experienced a partial response
  • Median duration of response to treatment was 14.8 months
  • In patients with brain metastases (24 patients), median progression-free survival (PFS, time to disease advancement) was 18 months
  • Adverse events (AE) occurred in all but one patient. The most common AE were nausea, hair loss, vomiting, constipation and neutropenia (low white blood cell count) 
  • 57% of patients experienced more serious (≥ grade 3) AE
  • 28.8% of patients stopped treatment due to disease progression
  • 15.2% of patients stopped treatment due to AE
  • One of the more serious complications, interstitial lung disease (ILD), was reported in 25 patients and 4 patients died due to ILD-related causes

Shortly after the study was presented, the drug received accelerated FDA approval for patients with unresectable (not able to be removed with surgery) or metastatic Her2 breast cancer who have experienced disease progression after treatment with 2 or more targeted agents. The approval is accompanied by a warning due to risks of ILD as well as embryo-fetal toxicity. 

ASCO Post coverage of trastuzumab deruxtecan

The other study involved Tucatinib, which is a tyrosine kinase inhibitor, administered in pill form. The Her2CLIMB trial* was a Phase 3 study that included patients with Her2 metastatic breast cancer who previously received treatment with trastuzumab, pertuzumab, and trastuzumab emtansine. Patients with and without brain metastases, including untreated brain metastases, were included. Patients in this trial received either tucatinib or placebo, in combination with trastuzumab and capecitabine (Xeloda – an oral form of chemotherapy).

The study included 612 patients. 410 received tucatinib-trastuzumab-capecitabine (T-C) and 202 received placebo-trastuzumab-capecitabine (P-C). 48% of patients in the T-C group and 46% of patients in the P-C group had brain metastases at enrollment. Median follow up was 14 months and findings included:

  • At one year, PFS was 33% in the T-C group and 12% in the P-C group
  • At one year, median duration of PFS was 7.8 months in the patients who received T-C and 5.6 months in the patients who received P-C
  • Overall survival (OS) at 2 years was 45% in the patients receiving T-C and 27% in those who received P-C
  • Median OS was 21.9 months in the patients receiving T-C and 17.4 moths in the patients who received P-C
  • Among patients with brain metastases, estimated PFS at one year was 24.9% in the T-C group and 0% in the P-C group
  • Among patients with brain metastases, median duration of PFS was 7.6 months in the T-C group and 5.4 months in the P-C group
  • The most common adverse effects in the patients in the T-C group were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting
  • 23 (5.7%) patients in the T-C arm and 6 (3.0%) patients in the P-C arm discontinued therapy due to side effects
  • Of the 215 deaths that occurred during the study, the most common reason was disease progression. Adverse events were the cause of death in 6 (1.5%) of patients in the T-C group and 5 (2.5%) in the P-C group

ASCO Post coverage of tucatinib

While these 2 studies demonstrate the progress that has been made in treating an aggressive form of breast cancer, they also serve as a sobering reminder of the work that remains. The hope with targeted therapy is that cancer cells will be killed with minimal toxicity to other cells or the person – we are not quite there yet. In addition, while the improvements in progression free and overall survival is encouraging, we are not yet able to ensure long-term survival for patients with metastatic Her2 breast cancer. If you donate to breast cancer research organizations, please consider this when deciding which groups to support.

*If you are not able to access the full studies and would like a copy, please email me: contact at drattai dot com

13 November 2019

The UCLA Center for Health Policy Research (UCLA CHPR) is developing a report on metastatic breast cancer, with the goal to drive actionable change in policy and practice. On Monday November 18th, the community will be asked to provide their thoughts for the UCLA CHPR team as part of their research study. The goal is to hear from patients, healthcare providers, researchers, caregivers, and advocates about the different types of barriers and challenges that patients with metastatic breast cancer may encounter when seeking and undergoing treatment. 

No idea too small or idealistic – we want creative, actionable solutions! The information gathered in this research study will be shared more broadly with other stakeholders, advocates, and policy makers. Please add your voice to this important conversation! This study has been funded by the California Breast Cancer Research Program

The study team may be contacted by sending an email to: ajscheitler@ucla.edu

If you’ve never joined a tweet chat, click here for information on how to participate in the conversation.

Discussion topics will include: 

  1. What are the most significant healthcare communication barriers faced by patients with metastatic breast cancer? 
  2. What are the most significant barriers to obtaining appropriate palliative care faced by patients with metastatic breast cancer?
  3. What are the most significant financial barriers faced by patients with metastatic breast cancer?
  4. What are the most significant barriers to obtaining disability faced by patients with metastatic breast cancer? 
  5. What health system or policy actions do you recommend to address barriers these barriers to care?
  6. Any other comments or suggestions! 

16 September 2019

The US Food and Drug Administration (FDA) has issued a safety announcement about a “rare but severe” lung inflammation that can result from the use of any of 3 breast cancer medications – palbocilcilb (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). These 3 medications are in a class of drugs called cyclin-dependent kinase (CDK) 4/6 inhibitors. They are used in estrogen receptor positive (ER+), Her2/neu negative metastatic (Stage 4) breast cancer, and work by interfering with cell division

The FDA announcement states that “the overall benefit of CDK 4/6 inhibitors is still greater than the risks when used as prescribed.” Palbociclib has been FDA-approved since 2015, and ribociclib and abemaciclib hae been approved since 2017. In evaluating studies of all 3 of the CDK 4/6 inhibitors, the FDA alert noted that 1-3% of patients taking these medications developed severe lung inflammation, and less than 1% died due to the condition.

The FDA recommended that patients notify their physicians immediately if they develop difficulty or discomfort with breathing or shortness of breath while at rest or at low activity when taking any of these medications. The FDA alert notes that there no specific risk factors that have been identified to determine how likely an individual patient is to develop severe lung inflammation while taking one of the CDK 4/6 inhibitors. They recommended that physicians routinely monitor their patients for lung symptoms that could indicate the development of severe inflammation. They also recommended that any side effects be reported to the FDA MedWatch Program. The alert noted that common side effects include “nausea, vomiting, diarrhea, constipation, decreased appetite, abdominal pain, infections, low red blood cell counts, low white blood cell counts, low platelet count, headache, dizziness, hair thinning or loss, rash, tiredness, and weakness”. I will post an update as more information becomes available.

Additional Information: