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%).2Testing 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.3Next 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.