Tuesday, September 16, 2014

The 2014 Breast Cancer Symposium was held September 4-6 in San Francisco. This is a unique meeting as it is multidisciplinary, co-sponsored by 6 organizations: the American Society of Clinical Oncology (ASCO), The American Society of Breast Surgeons (ASBrS), the Society of Surgical Oncology (SSO), the American Society for Radiation Oncology (ASTRO), the National Consortium of Breast Centers (NCBC) and the American Society of Breast Disease (ASBD). This is a unique meeting as it brings together all of the specialists involved in treating patients with breast cancer.
As usual, this was a well-attended meeting. Many interesting abstracts were presented, and the general sessions covered timely issues related to the care of breast cancer patients. However, I did hear several patients and advocates (via twitter) who were in attendance express frustration about the lack of consensus for management of certain conditions, the focus on obesity and exercise as methods to reduce the risk of disease development and recurrence, and the lack of “real” progress.
Unfortunately, while we currently know more about breast cancer than at any other point in time, meetings like this reinforce that what we know is just the tip of the iceberg – cancer is incredibly complex. Various pathways have been identified as targets for treatment, but no one treatment will work in all patients. Targeted therapies, immune system modulators, and other novel treatments are in development, but may not come fast enough for the individual patient, especially those living with metastatic disease. Trust me, this is just as frustrating for the physicians as it is for patients. But this is also what motivates us to keep asking questions and researching, until we have some real solutions – ones that work for everyone.
Some of the topics that stood out for me:
Mammography and MRI screening: we are trying to identify which women should be screened and with what technology (mammogram, ultrasound, MRI). Personalized screening based on an individual’s risk is the ideal, but we cannot yet truly pinpoint an individual patient’s risk. Even in those with BRCA gene mutations, not all will develop breast cancer. Dr. Steven Feig discusses that personalized screening must be based on only well-established medical knowledge.
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Can we identify patients with breast cancer who do not need treatment? We know that many early-stage breast cancers, especially ductal carcinoma in-situ (stage 0 breast cancer, or DCIS) will never progress to invasive disease, and are not a threat to a woman’s breast or life. DCIS Treatment vs. Observation was the subject of a debate between Drs. Henry Kuerer (MD Anderson) and Shelly Hwang (Duke University). Both surgeons made excellent points, but in the end, there was no consensus on how to identify an individual patient who would not progress without treatment. The best we can do right now is use assessments of tumor biology, volume of disease, and patient factors to help guide discussions with our patients.
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An excellent talk was given by Dr. Susan Boolbol (Mount Sinai Beth Israel in New York) on genetic testing. A key point made is that all cancer is genetic, but not all cancer is hereditary. All cancers have at their core a mutation in one or more genes, but not all cancer-inducing mutations are passed down from one generation to the next.  Approximately 5-10% of breast cancers are hereditary; the majority are sporadic. Taking a thorough family history is essential to provide a cancer risk assessment, to identify other family members who may be at increased risk, and to recommend risk management options such as increased surveillance, genetic testing, chemoprevention and prophylactic surgery.
Red flags for hereditary breast cancer –
-       3 or more family members with the same or similar type of cancer
-       2 or more generations affected
-       1 or more cancers diagnosed before age 50
BRCA 1 and 2 are the most common DNA repair genes; there are 2 copies in each cell. When one copy of BRCA 1 or 2 is defective, other malignant DNA mutations (which occur from time to time for various reasons) cannot be repaired, which leads to uncontrolled cell reproduction and cancer growth.  Approximately 1 in 500-800 patients in the general population are estimated to have a BRCA 1/2 mutation; in patients of Ashkenazi Jewish ancestry, approximately 1 in 40 may carry a mutation.
When possible, the family member who has had cancer should be tested, and if a mutation is found, then other family members can undergo targeted testing. If testing is negative, counseling is still required as it can have a variable meaning depending on the overall family history. The risk of breast and ovarian cancer development depends on the specific mutation as well as the age of the patient.  Contralateral (opposite side) breast cancer incidence is increased, and is also related to age of the patient and her age at initial diagnosis.
Dr. Boolbol touched on the 2013 Supreme Court decision regarding gene copyrights. This has increased the number of companies offering genetic testing.  Many companies now offer extended panel testing, as it is recognized that other gene mutations may also be responsible for breast cancer development. However, guidelines for treatment do not necessarily exist for many of these other mutations (such as PALB2). An additional caution in evaluating any genetic test results is that an abnormal test may not necessarily indicate an increased risk of developing breast cancer. Some of the mutations detected (including in the BRCA 1/2 genes) may be variants of unknown significance (VUS) which may or may not lead to an increased risk of breast and/or other cancers.  It is important for patients undergoing genetic testing to have thorough consultations with their physicians and/or a genetic counselor, as “not all genetic mutations are created equal”.
Dr. Banu Arun from MD Anderson discussed the management of patients with hereditary mutations or who are otherwise considered to be high-risk.  Options include surveillance / screening, prophylactic surgery, and chemoprevention.
For surveillance / screening, clinical breast exams (an exam by your physician) is recommended every 6-12 months starting around age 25. Annual MRI is recommended from age 25-29 (mammogram if MRI not available), annual mammogram and MRI age 30-75, and after age 75 individualized management is recommended.  These recommendations may change depending on a relative’s age at diagnosis. Note that at this point, the 2014 NCCN guidelines do not specify the use of screening ultrasound although it is often used.
Preventive mastectomy can reduce the risk of breast cancer by >95%. Patients already diagnosed with breast cancer  may have as high as a 65% risk of developing a contralateral breast cancer which is why bilateral mastectomy is often recommended. A bilateral salpingo-oophorectomy (BSO – removal of the ovaries and fallopian tubes) can reduce the risk of breast cancer by 50%, and is ideally performed between age 35-40 (for maximum breast cancer risk reduction).  BSO is also associated with a 95% reduction in the risk of developing ovarian cancer.
75% of BRCA1 related breast cancers are ER negative; 58% are triple negative. Studies evaluating tamoxifen for chemoprevention in BRCA positive patients have conflicting results.
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Dr. Ann Partridge from Dana Farber discussed the non-medicinal approach to risk modification. Opportunities to modify risk factors include reducing exposure to environmental toxins and health behaviors. Much of the research to date has focused on individual points in time, but current research is focusing on the exposure a woman faces over her lifetime.
Modifiable exposures include radiation exposure, exposure to contributor chemicals, combination hormone replacement therapy, active / passive smoking, alcohol intake, and diet.
Exercise and weight control are crucial to helping to reduce the risk of breast cancer – we’ve all heard this many times, but the evidence continues to grow. Clearly this is not the only factor – we all know women who exercised regularly and still developed breast cancer – but it is important. The benefit appears to be with 3+ hours of moderate paced walking per week. No studies have looked at survival benefits to weight training, but weight training does help with overall weight maintenance.
Interestingly, a low body mass index (BMI) as a young adult or premenopausal woman is associated with an increased breast cancer risk, yet in postmenopausal women, an elevated BMI is associated with an increased breast cancer risk. The reasons are unclear, but Dr. Partridge did not recommend that premenopausal women gain unhealthy amounts of weight!
It’s very challenging to study nutrition and cancer. Many food items are inter-related, and nutrition is often related to weight and other health behaviors.  Long-term dietary habits are more important than short-term, and she reinforced that the concept of a “magic bullet” is not likely. She also cautioned about over-interpreting the results of small nutritional studies.  Regarding alcohol, there does not seem to be any increased risk of breast cancer with consumption of <3 drinks per week, but increased consumption is associated with an increased risk.
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The metastatic breast cancer tumor board was also a good session. As with the other sessions, there was no true “news”. However, it was a good example of the multidisciplinary discussions that we all have with our colleagues in order to decide what treatment options are best for an individual patient.  Dr. Ben Anderson (a surgical oncologist with Seattle Cancer Care Alliance) also stressed that the patient needs to be treated, not the disease – we need to work with our patients to get their thoughts on quality of life and symptom control, and then tailor our treatments to their preferences.
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Finally, I had the opportunity to present the #BCSM research as a poster. Based on the survey earlier this year, we found that knowledge regarding various aspects of breast cancer increased, and anxiety was diminished. Obviously these are the results as a whole, and as they say, “individual results may vary”.  I believe we have a lot to do to improve this community, but these results tell me that we’re on the right track.

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