ASCO: Treating BRCA-Positive Breast Cancer

Susan M. Domchek, MD

As part of our coverage of the 2014 American Society of Clinical Oncology (ASCO) Annual meeting, being held May 30–June 3 in Chicago, we spoke with Dr. Susan Domchek, professor of oncology and director of the Basser Research Center, who specializes in breast cancer genetics, screening, and treatment at the University of Pennsylvania in Philadelphia. Dr. Domchek discussed treatment strategies for treating patients with both early and advanced breast cancer who harbor either the BRCA1 or BRCA2 mutation in a presentation at the meeting.

  -Interviewed by Anna Azvolinsky  

Cancer Network: What are the current recommendations for cancer screening and prophylaxis for those women who harbor a germline BRCA1 or BRCA2 mutation?

Dr. Domchek: We generally divide our recommendations into the management of breast cancer and ovarian cancer risk. For breast cancer risk, we discuss starting MRI breast cancer screening at age 25, with the addition of a mammogram at around age 30. In addition, women can chose to have a bilateral mastectomy and the benefit of this is discussed extensively with patients. For ovarian cancer risk, we do certainly recommend prophylactic removal of the ovaries. This decreases the risk of both ovarian cancer, the risk of breast cancer, and also is associated with an improvement in overall survival. So the real keys are screening of breast cancer, prophylactic removal of the ovaries, and the option for a bilateral mastectomy.

Cancer Network: Since the Supreme Court ruling partly invalidating the patent on the BRCA genes, there are now several commercial laboratories that offer commercial BRCA screening tests, providing new testing options. Has this changed screening practice at all, or is there a trend toward a change that you see in practice?

Dr. Domchek: The decision has certainly opened up competition in the testing field and there are now multiple companies who offer BRCA1 and BRCA2 testing. There are a lot of options out there, and it is also dependent on the patient’s insurance company [coverage], because some patients are confined to specific testing laboratories. With regard to cost, the cost can be different across laboratories, although most patients have insurance coverage for their genetic testing. So it is really a matter of working with your provider to figure out what makes the best sense given your insurance and co-pays-to decide which lab you may wish to use. There are a lot of good options, and that is always good for patients. 

Cancer Network: In terms of treatment management, for those women with localized BRCA-positive breast cancer. What is the typical management of the disease?

Dr. Domchek: One of the issues we always deal with when it’s a younger patient, or woman of any age with a strong family history who may be at risk for carrying a BRCA1 or BRCA2 mutation, is how that may affect what a clinician does at the time of initial diagnosis. And there are a few things that we consider. If a woman has a breast cancer diagnosis, she is at increased risk for developing a second breast cancer, either in the other breast or in the same breast at a later time. So that can impact local therapy decisions. There are definitely many women who chose to have a bilateral mastectomy at the time of their initial diagnosis rather than, for instance, a lumpectomy and radiation therapy. And this is really a specific issue in BRCA1/2 mutation carriers, because there is a very high risk of a second primary breast cancer. The other factor to consider is an oophorectomy or a removal of the ovaries in this situation. Again, ovarian cancer is a real issue and we know that women with breast cancer who have these gene mutations are at risk of developing ovarian cancer and therefore, dependent on a patient’s age and where she is in her reproductive decision making, an oophorectomy can be incorporated into that initial surgical planning decision. In terms of other systemic therapy options, that is more in flux at this time. Regarding pre-operative and adjuvant therapy there are a number of sets of evolving data regarding this issue. There are studies looking at platinum regimens, pre-operative chemotherapy for mutation carriers, and that is something that we are all trying to nail down-the exact benefit of doing something like that. 

Cancer Network: What about management of patients with advanced disease?

Dr. Domchek: For women who have metastatic breast cancer related to BRCA1/2, there are two main issues that we consider. One is the role of platinum therapy. There are some data that the use of platinum is associated with higher response rates, particularly for BRCA1-associated metastatic breast cancer. So it is very reasonable to at some point, incorporate platinum therapy. The other major issue is the evolution of clinical trials using PARP inhibitors. There are a large number of clinical trials that are open or about to open looking at PARP inhibitors in BRCA-associated metastatic breast cancer. And in this situation, it is important to realize that a lot of those PARP inhibitor trials are now aimed at more early-stage situations, first- or second-line, and some also in third-line disease. Some trials also restrict prior platinum use, so trying to really identify BRCA carriers and investigating options for clinical trials is quite important. There is a great deal of interest in clinical trials in BRCA1 and BRCA2 mutation carriers right now, but this is not a super common patient population, and so folks need to look out for potential clinical trials to get their patients referred to these studies.

Cancer Network: Are there any study results from trials focusing on the BRCA mutation carrier population at this year’s ASCO meeting that you would like to highlight?

Dr. Domchek: Well there were 91 abstracts that included the term BRCA, which is very exciting for our field, to see the explosion of research in this area. There are certainly studies looking at PARP inhibitors, either follow-up from studies or ongoing studies that are being highlighted at the meeting. Again, these are mostly PARP inhibitor trials. There is also a study from our group (abstract 1508) looking at the impact of oophorectomy on the quality-of-life measures in BRCA carriers, and the point there is that, unfortunately, people do have a detriment in their quality of life related to a prophylactic oophorectomy. Like everything we do in oncology, there are risks and benefits, and we need to balance these. Finally, there is provocative data (abstract 1507) on the potential of an oophorectomy to impact breast cancer-specific survival in BRCA1 and BRCA2 mutation carriers, which is very interesting data, but as mentioned, an oophorectomy is strongly recommended based on the ovarian cancer risk alone, and a lot of what we need to do is to figure out optimal timing and ways to minimize the negative consequences of that procedure.

Cancer Network: Thank you so much for joining us today, Dr. Domchek.

Dr. Domchek: Thank you.