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.
https://drattai.com/wp-content/uploads/2019/11/centerLogo.jpg6191326drdeannaattaihttps://drattai.com/wp-content/uploads/2019/06/logo.pngdrdeannaattai2019-11-14 02:37:582019-11-15 17:04:02Public Policy and Metastatic Breast Cancer
Especially during October, when everything seems to be painted pink, it’s easy to overlook the fact that breast cancer is a disease of women and men. Male breast cancer accounts for 0.6 – 1.0% of all breast cancer cases. In the US, approximately 2600 men will be diagnosed with breast cancer each year. The lifetime risk is about 1 in 1000, versus 1 in 8 for women. Male breast cancer accounts for approximately 500 deaths in the US per year. Risk factors include increasing age, family history including BRCA gene mutations, obesity, alcohol intake, prior chest wall radiation, and low androgen hormone levels.
Male breast cancer tends to be diagnosed in later stages compared with breast cancer in women, and previous studies have come to conflicting conclusions about whether the poorer outcomes are due to higher stage at diagnosis or other factors. A study recently published in JAMA Oncology* looked at mortality rates among men and women diagnosed with breast cancer. The researchers used the National Cancer Database (NCDB) and compared men and women who were diagnosed with breast cancer between January 2004 – December 2014. Their data analysis included approximately 16,000 men and 1.8 million women. Some of the key findings:
Mean age at diagnosis was 63.3 for men and 59.9 for women
3-year survival was 86.4% for men and 91.7% for women
5-year survival was 77.6% for men and 86.4% for women
Overall survival was 45.8% for men and 60.4% for women
Men diagnosed with breast cancer were older, were more likely to be diagnosed at advanced stages, and were less likely to receive conventional therapy. However, differences in survival persisted even after controlling for clinical characteristics of the disease, age, race and ethnicity, and access to care. Limitations of this study are that cause of death could not be determined (so it is not clear if all of the deaths are related to breast cancer) and the NCDB does not contain information on recurrence, BRCA gene status, adherence to treatment recommendations, and other medical conditions. However, the researchers concluded that male sex remained a significant risk factor for poorer outcomes, which suggests that there are biological differences in male versus female breast cancer.
Another study recently published in the journal Cancer* also used NCDB information to look at treatment trends for men treated for breast cancer from a similar time period. The authors evaluated approximately 10,000 cases and noted that:
24% underwent breast conserving surgery (lumpectomy)
70% of those undergoing lumpectomy received radiation
44% of patients received chemotherapy
62% of those with estrogen receptor positive (ER+) breast cancer received endocrine therapy
35% of those with ER+ / lymph node negative breast cancer had Oncotype Dx testing on their tumor to help determine need for chemotherapy
These findings are consistent with a point made in the JAMA Oncology study noting that men were less likely to receive conventional therapy – for example only 62% with ER+ breast cancer received endocrine therapy and only 70% of those undergoing breast conserving surgery were treated with postoperative radiation therapy. Some of the same limitations apply to this study, in that reasons for differences in therapy could not be determined, and there was no information on disease recurrence.
A few other important points to make about male breast cancer:
Most male breast cancer presents as a lump, but as in women, most lumps are not cancerous. It is important that a proper evaluation (usually including a mammogram and ultrasound, and possibly biopsy) be performed for any change
As in women, male breast cancer may present with nipple discharge (especially blood), “puckering” or “pulling in” of the skin, or severe redness of the skin which can be mistaken for infection – the latter may indicate a more aggressive type of breast cancer known as inflammatory breast cancer
ALL men with breast cancer, and anyone with a family history of male breast cancer, should undergo genetic counseling and testing. As in women, most cases of male breast cancer are “sporadic” (not related to an inherited mutation), but men with breast cancer are more likely to carry deleterious BRCA (especially BRCA 2) mutations
Men who carry a deleterious BRCA mutation have an approximately 8% lifetime risk (to age 80) of developing breast cancer. So while that is considered “high risk” for men, they are still more likely to NOT develop breast cancer. We do not currently recommend prophylactic mastectomy in men who carry a deleterious BRCA mutation but who have not been diagnosed with breast cancer
Men who carry a deleterious BRCA mutation are also at higher risk for prostate cancer, melanoma, and pancreatic cancer
Men with breast cancer are usually treated using the same protocols that are used for women. Unfortunately there is limited data to support this. Male breast cancer is not common, so it is challenging to enroll large numbers of patients in clinical trials. However, men have historically been excluded from many breast cancer clinical trials, so how can we even make progress? The US FDA has recently issued draft guidelines encouraging the inclusion of male breast cancer patients in clinical trials – this is certainly a step in the right direction.
*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com
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Mastectomy (breast removal) rates continue to increase in the US. While reconstructive surgery is commonly performed after mastectomy, some patients opt to “go flat” or have no reconstruction. Some patients who have had reconstruction need to or choose to have the reconstruction reversed.
The aim of this study is to survey the “Going Flat” patient communities to assess patient satisfaction with their decision and results.
This survey is being conducted for research purposes. It is a UCLA research survey.
Patients should meet one of the following criteria to participate:
Single or double mastectomy for any reason (including if lumpectomy was performed first) and decided not to have reconstruction (decided to “go flat”)
Single or double mastectomy for any reason (including if lumpectomy was performed first), initially had reconstruction but then had reconstruction reversed or removed for any reason
This survey is voluntary and is completely anonymous. No identifying information, including internet protocol (IP) addresses, will be collected. There is no industry funding or sponsor for this survey. The survey should take approximately 15 minutes to complete. We value your time and your opinions. The anonymous data will be securely stored by the principal investigator and may be used for future research studies.
By mail: 191 S. Buena Vista #415 Burbank, CA 91505
UCLA Office of the Human Research Protection Program (OHRPP): If you have questions about your rights as a research subject, or if you have concerns or suggestions and you want to talk to someone other than the researchers, you may contact the UCLA OHRPP
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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.
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Last week, the US Food and Drug Administration (FDA) issued draft guidelines for industry, which encourage the inclusion of male breast cancer patients in clinical trials that evaluate breast cancer therapies. The guidelines note that “eligibility criteria for clinical trials of breast cancer drugs should allow for inclusion of both males and females” and that “scientific rationale should be included in the protocol when proposing to exclude males from breast cancer trials.” There is a 60-day open comment period on the guideline.
In the US, approximately 2600 men are diagnosed with breast cancer each year, approximately 1% of all new breast cancer cases. Men tend to be diagnosed at more advanced stages compared with women, and there are about 500 male breast cancer related deaths in the US annually. Breast cancer in men is usually treated in a similar manner as in women. However, because men are typically not included in breast cancer clinical trials, it is not known if this is an optimal approach. One of the primary reasons that men are excluded from breast cancer clinical trials is that the disease is uncommon – setting up a vicious cycle where little progress is made. The statement noted that “FDA does not intend to consider low expected accrual rates of male patients with breast cancer to be a sufficient scientific rationale for excluding them from a clinical trial.”
This is most certainly a welcome step towards improving the understanding and treatment of male breast cancer.
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The FDA announcement notes that 573 cases of BIA-ALCL have been diagnosed worldwide, and the majority of the cases (481) have been linked to Allergan implants. While BIA-ALCL is thought to be curable by removing the implant and capsule, the FDA announcement reports that 33 patients have died. In 13 of the cases (of patient death) where the implant manufacturer was known, 12 patients had Allergan implants. The FDA announcement was prompted by information received since March 2019, when the FDA issued a letter to healthcare providers and held a public meeting to increase awareness of BIA-ALCL and to request that suspected cases be reported.
The plastic surgeon’s office typically keeps a record of the type of implant placed. Today’s FDA announcement stated that the majority of implants placed in the US are NOT the textured form, and that the specific type of Allergan implant implicated accounts for about 5% of all implants placed in the US. BIA-ALCL is not common, and typically presents with rapid accumulation of fluid (that a patient would notice as swelling) sometime after placement. As always, report any changes to your physician.
Update after 7/25/19 FDA call: I had the opportunity to sit in on a call with the FDA and several other surgical societies this morning and a few points were made:
The implants implicated in the recall were not marketed in the US prior to March 2000.
A small percentage of cases of BIA-ALCL have occurred in patients who have no history of textured implants.
Tissue expanders, the temporary “spacers” that are often used prior to stretch the skin and muscle, are often textured. They are not usually left in place for more than a few months, but the FDA did not have any information or insights as to whether these might be the cause of BIA-ALCL in patients with no history of textured implants.
The FDA is not recommending removal of implants in asymptomatic patients. They stressed that if implants are removed, the implant capsule (the fibrous scar tissue that normally forms after implant placement) also needs to be removed, because that is where the ALCL develops.
It was discussed that there is no “early detection” for BIA-ALCL, and that patients may not be comfortable with a “watch and wait” approach.
Concerns were raised about insurance coverage for implant removal and replacement, especially in patients who are asymptomatic. The FDA commented that insurance coverage issues are out of their scope of practice but they recognize the problem. They did note that they had met with patient advocate groups earlier today
All of the representatives from the surgical organizations that were on the call agreed that education of their members as well as the larger physician community is necessary. A representative from the American Society of Plastic Surgeons noted that they have been educating their members for some time and have patient resources on their website. They also stressed that if patients note any changes, they should seek out a board-certified plastic surgeon
Symptoms of BIA-ALCL include the sudden development of swelling (due to fluid accumulation) with or without a mass. Any changes should be promptly reported.
We tend to think of most cancers as a single cell line, or clone – one normal cell develops a mutation, and that abnormal cell continues to divide. However, many tumors exhibit what is termed “heterogeneity” – meaning they are composed of cells with different genetic makeups. These cells can have different behaviors, growth patterns and response to treatment.
A study recently published in the Annals of Surgical Oncology looked at the association between tumor heterogeneity and immune cells. They found that tumors with high heterogeneity (more diverse cell population) were associated with worse overall survival. They also found that these tumors were associated with lower levels of anti-tumor T-cells (an immune system cell) and “immune checkpoint molecules”, and had a higher percentage of immunosuppressive T-cells. Their finding was noted primarily in estrogen-receptor positive (ER+) breast cancers.
Testing for different cell populations within a tumor is not routinely performed at this point in time. In addition, the authors noted that it is up for debate (and further research) which comes first – do the diverse tumor cell populations attract immune cells, or do the immune cells act to control tumor cell diversity. They noted that additional work is needed to better understand the changes that influence tumor cell heterogeneity and to develop methods to prevent it from occurring. This is just one of the reasons why a “cure” for cancer is not that simple. Cancer – even a single tumor in one patient – is not just one disease.
Note – if you would like a copy of the studies discussed below but are not able to access them from the journal website, please email me: contact at drattai dot com
In a study recently published in the Annals of Surgical Oncology, Bateni et al used the National Cancer Database to assess outcomes in patients with male breast cancer based on surgical therapy. The authors found improved 10-year survival in patients who underwent breast conserving therapy (BCT) which they defined as partial mastectomy (also called lumpectomy) plus radiation therapy.
Male breast cancer makes up about 1% of all new breast cancer diagnoses; approximately 2500 men are diagnosed in the US each year. Treatment guidelines for male breast cancer are similar to those for post-menopausal women despite growing evidence that breast cancer in men is a biologically different disease versus that in women. One of the challenges for clinical trials is the relatively small numbers of male breast cancer patients diagnosed each year. However, many clinical trials have not included men.
A total of 8445 patients with stage I and II breast cancer, treated between 2004-2014, were included for analysis. 61% underwent mastectomy, and 18% underwent BCT. 12% had mastectomy with radiation, and 8% had partial mastectomy without radiation. Median follow up was 52 months. At 10 years, overall survival was as follows:
56% mastectomy with radiation
56% partial mastectomy without radiation
The image below is Figure IA from the manuscript, which show the “crude” overall survival for male breast cancer patients depending on surgical therapy.
Evaluating patients who had breast conservation with or without radiation, the authors noted that patients who were older, had higher tumor stage, higher cellular grade, and triple negative histology had poorer overall survival rates. They noted that there were differences in patient age, co-morbidities (other medical conditions), margin status and chemotherapy use for patients who underwent BCT versus partial mastectomy alone. However, after accounting for these differences, survival rates still favored BCT, suggesting that radiation therapy is an important component of improved outcomes.
Limitations of the study noted by the authors include the retrospective nature, and the inability to understand some of the factors that influenced the decision for mastectomy versus breast conservation. Her2/neu status was not uniformly reported in the NCDB until 2010, so almost half of the patients in this study did not have this information. They also noted a larger percentage (4.9 vs 1.4%) of patients in the BCT group had triple negative breast cancer, which might explain why more of these patients were also treated with chemotherapy. It is also not clear how much of an influence the use of chemotherapy and endocrine therapy had in terms of the survival rates that were noted.
In a separate article, De La Cruz et al performed a systematic literature review of the studies evaluating breast conservation in men (excluding the Bateni et al study discussed above). The authors found 8 publications meeting their criteria. Among these studies, there were 859 patients who underwent breast conservation, 14.7% of all male breast cancer surgeries in the combined papers. Reporting on the “weighted average”, local recurrence (cancer returning in the breast) was 9.9%, disease-free survival was 85.6% and 5 year survival was 84.4%. As with the retrospective database analysis, there are limitations to this type of literature review – studies may use the same data points for inclusion, including use of radiation therapy, chemotherapy, and margin status. There may be significant differences in the patient populations in the various studies reviewed. As in the Bateni et al paper, there may be multiple unknown factors that influenced a decision for surgery type.
Men tend to present with larger tumors, especially relative to breast size, so often mastectomy is recommended. However, the authors of both papers were of the opinion that breast conservation is oncologically safe and a very reasonable option for men with early stage breast cancer, if they desire. Bateni et al stressed the importance of radiation therapy if breast conservation is utilized. Both papers highlight the importance of clinical trials for male breast cancer, so that treatment recommendations can be based on the best available evidence.
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The MONALEESA-7 Phase III trial evaluated the use of ribociclib in combination with endocrine therapy. Patients who received ribociclib and endocrine therapy were found to have improved overall survival rates compared to those who received endocrine therapy alone. Prior studies demonstrated improved progression free survival, but this was the first demonstration of an improvement in overall survival. Patients enrolled in this study were pre- or peri-menopausal.
Ribociclib is an oral medication belonging to the CDK 4/6 inhibitor class of targeted agents. The CDK 4/6 pathway is important for cell division. CDK 4/6 inhibitors block progression through the normal cell cycle, so cancer cells are “arrested” in a resting phase and cannot divide. This study found that at 42 months, patients treated with ribociclib had a 70% overall survival rate, compared to 46% for the patients who received endocrine therapy alone. In absolute numbers, there were 26 fewer deaths (83 or 337 versus 109 of 335) in the treatment group. Because patients who develop metastatic breast cancer after a diagnosis of early-stage disease are not re-staged, it is not possible to determine with certainty how many patients this medication may be appropriate for. Approximately 40,000 women and 500 men die from metastatic breast cancer every year. ER+ is the most common breast cancer subtype.
Prior studies have evaluated a similar drug, palbociclib, which has been approved for use in women and men with metastatic breast cancer. There are ongoing studies evaluating all 3 of the “ciclib” agents to get a better sense of whether the results will be similar across all patient populations or if a particular drug will be better for a particular subset of patients. All 3 agents are oral (pills). While side effects may be an issue for some patients, these medications are much better tolerated compared to traditional chemotherapy. Unfortunately, cost and insurance coverage may be an issue in some situations.
In addition, I do think that it is important to point out that in the current study, the majority of patients (67% in the ribociclib arm and 73% in the endocrine therapy alone arm) went on to receive other therapy – meaning that the disease progressed. We are still a long way from a “cure” despite improvements in overall survival, and we’re a long way from single-agent therapy in patients with metastatic breast cancer. Patients with metastatic breast cancer are still expected to need more than one, and in some cases multiple, agents over time as the cancer finds ways to mutate and continue to grow. The findings of this study are a step in the right direction, but much more research is needed.
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Note – the survey closed on July 7th 2019. Thank you to all who participated and shared, and we will be sure to post the results when they are available!
Approximately 25-30% of patients with breast cancer who are prescribed endocrine therapy do not complete the full course of treatment, and some patients never start. Side effects of endocrine therapy are well documented but there is very little literature on the role of the medical team in helping patients manage treatment-related side effects.
This survey is being conducted for research purposes. It is a UCLA research survey, open to women and men with a history of breast cancer who have been treated with or who have received a recommendation for endocrine therapy.
This survey is voluntary and is completely anonymous – no identifying information, including internet protocol (IP) addresses, will be collected. The survey should take approximately 15 minutes to complete. We value your time and your opinions.
For questions regarding this study, you may contact principal investigator Dr. Deanna Attai By phone: (818) 333-2555; by email: email@example.com; or by mail: 191 S. Buena Vista #415, Burbank, CA 91505
UCLA Office of the Human Research Protection Program (OHRPP): If you have questions about your rights as a research subject, or if you have concerns or suggestions and you want to talk to someone other than the researchers, you may contact the UCLA OHRPP By phone: (310) 206-2040; by email: firstname.lastname@example.org; or by mail: Box 951406, Los Angeles, CA 90095-1406
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This website does not provide medical advice and should not be used to diagnose or treat any medical condition. The opinions expressed on this website are those of Dr. Attai and do not reflect the views of the University of Southern California Los Angeles or the David Geffen School of Medicine. Dr. Attai does not consult for or have financial relationships with any websites, companies or products, including those that are referenced on this website.