BRCA Testing and Contralateral Prophylactic Mastectomy

Oncology & Biotech News, January 2015 , Volume 9, Issue 1

In Partnership With:

Partner | Cancer Centers | <b>Wake Forest Comprehensive Cancer Center</b>

Determination of BRCA1 and 2 mutation carrier status has become increasingly important. Estimates suggest that about 80% of breast cancers and 90% of ovarian cancers are sporadic; while only 5% to 10% of breast cancers are hereditary.

Marissa Howard-McNatt, MD

Director, Breast Care Center, Associate Professor Surgery, Comprehensive Cancer Center at Wake Forest Baptist

Determination of BRCA1 and 2 mutation carrier status has become increasingly important. Estimates suggest that about 80% of breast cancers and 90% of ovarian cancers are sporadic1; while only 5% to 10% of breast cancers are hereditary. Hereditary mutations of the BRCA1 and BRCA2 genes account for 60% of inherited breast and ovarian cancers.1 According to recent data, the risk of a BRCA2 mutation carrier developing breast cancer by age 70 years is 45%, and her risk of developing ovarian cancer is 11% to 17%; BRCA1 mutation carriers have a slightly higher risk of breast cancer (55%-65%) and a higher risk of ovarian cancer (39%).2

Testing for BRCA Mutation Status

In our multidisciplinary breast center, we routinely test women who are at high risk for harboring a BRCA mutation. Genetic counselors play a vital role in identifying and evaluating women who are at high risk for hereditary breast cancer syndromes. For a woman with a known cancer, counseling and testing may help her decide whether to undergo a bilateral mastectomy at the time of her cancer surgery, or whether to opt for careful surveillance of the remaining breast tissue.

The National Comprehensive Cancer Network (NCCN) has well-established criteria for consideration of BRCA 1/2 testing among women with a recent breast cancer diagnosis, including the presence of young age (<45 years), bilateral breast cancers, a family history of male breast cancer, and a significant family history of breast and/ or ovarian cancer.3 The NCCN guidelines have formally included triple-negative breast cancers among women aged <60 years as additional eligibility criteria for consideration of genetic testing.3

Next Steps After BRCA Testing

If a BRCA mutation is discovered, then we recommend bilateral prophylactic mastectomies with bilateral oophorectomies or close observation with breast MRI and transabdominal ultrasound with chemoprevention. Some women who test negative for the mutation still opt for bilateral mastectomies.

The rate of contralateral prophylactic mastectomy (CPM) has more than doubled over the last decade, both in invasive breast cancer and ductal carcinoma in situ.4 It has been suggested that CPM may increase cancer-specific survival. A recent retrospective study showed the CPM was associated with an improved disease-free (P = .0002) and overall survival (P = .03) at 17 years.5 However, the majority of studies over the past decade show inconsistent survival advantage. These studies are retrospective in nature.

There are no prospective studies that have examined survival benefit with CPM and there will likely never be a randomized trial of CPM. From a patient’s prospective, choosing a contralateral prophylactic mastectomy is driven by the fear of recurrent breast cancer.6 CPM substantially reduces the risk of developing contralateral breast cancer. However, the risk of systemic metastases from the incident cancer often outweighs the risk of contralateral breast cancer. Thus, many patients may not have a clear understanding of the actual survival benefit from a CPM.

Prospective Analysis of BRCA Testing and CPM

Given the increasing use of CPM and genetic testing, we performed a prospective study looking at preoperative BRCA testing and the use of CPM. We sought to understand the factors before and after genetic testing that contribute to a breast cancer patient’s decision to have a CPM despite being BRCA negative. We performed a demographic and qualitative questionnaire for stage 0 to III female breast cancer patients.7 Data collection after initial diagnosis of breast cancer was done prior to genetic testing and surgery, and 6 months following surgery. Only women who tested BRCA negative and chose a CPM were given the 6-month survey.

From 2010 to 2014, one hundred women were prospectively enrolled in the study. Women who chose CPM presented at a higher stage (P = .012). A BRCA mutation was found in nine women. Twenty-six women who were BRCA negative chose to undergo a CPM. Compared with women who did not have a CPM, women who underwent a contralateral mastectomy presented at a higher stage (P = .0157) and had invasive ductal carcinoma (P = .05). Twelve women who initially chose a unilateral mastectomy changed their surgery to CPM after genetic testing (P = .0023). We asked them why they chose to have a CPM. The main reason was to be alive for their children.

This is the first prospective study examining genetic testing, surgical choice, and CPM. BRCA-negative women were more likely to have a CPM if they presented at a higher stage and initially chose a unilateral mastectomy. Preoperative genotyping resulted in a significant change in a woman’s surgical choice. We believe that patients need to be educated about the role and perceived survival advantage of CPM and genotyping as part of their surgical decision making.

Genetic testing for cancers is an increasing field. With the inception of new tools such as Myriad myRisk™ Hereditary Cancer 25-gene panel, we can now identify eight primary cancer sites a patient is at risk for inheriting, including breast cancer. The role of the breast surgeon, multidisciplinary team, and genetic counselor will increase in helping women to understand what these genes mean and to accurately evaluate their risk of systemic and contralateral disease.

References

  1. Daly MB, Axilbund JE, Buys S, et al. Genetic/familial high-risk assessment: breast and ovarian. J Natl Compr Cancer Netw. 2010;8(5):562—594.
  2. Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117—1130.
  3. National Comprehensive Cancer Network, NCCN Guidelines. Version 2.2013. Hereditary Breast and/or Ovarian Cancer Syndrome. NCCN.org.
  4. Tuttle TM, Habermann EB, Grund EH, et al. Increasing use of contralateral prophylactic mastectomy for breast cancer patients: a trend toward more aggressive surgical treatment. J Clin Oncol. 2007;25(33):5203-5209.
  5. Boughey JC, Hoskin TL, Degnim AC, et al. Contralateral prophylactic mastectomy is associated with a survival advantage in high-risk women with a personal history of breast cancer. Ann Surg Oncol. 2010;17(10):2702—2709.
  6. Herrinton LJ, Barlow WE, Yu O, at al. Efficacy of prophylactic mastectomy in women with unilateral breast cancer: a cancer research network project. J Clin Oncol. 2005;23(19):4275- 4286.
  7. Howard-McNatt M, Isom S, Hurt G, et al. A prospective study of preoperative BRCA status determination and surgical choice. Accepted abstract to be presented at: Society of Surgical Oncology 2015 Annual Cancer Symposium; March 25- 28, 2014; Houston, TX.

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