EBCC-11: Double Mastectomy in BRCA1 and BRCA2 Carriers

Key Points

  • At the age of 65, overall survival among BRCA1 mutation carriers was 90% in the bilateral risk-reducing mastectomy group compared to 83% in the surveillance group. At the same age, breast cancer–specific survival was 99.6% in the bilateral risk-reducing mastectomy group compared to 93% for the surveillance group.
  • In BRCA2 mutation carriers at the age of 65, while overall survival was 95% for the bilateral risk-reducing mastectomy group compared to 88% for the surveillance group, breast cancer–specific survival was 100% for the bilateral risk-reducing mastectomy group compared to 98% for the surveillance group. 

Healthy women who carry a breast cancer–causing mutation in the BRCA1 gene not only reduce their risk of developing the disease but also their chances of dying from it if they have both breasts removed, according to new research presented at the 11th European Breast Cancer Conference (EBCC-11) (Abstract 134). However, the study also found that for women with a mutation in the BRCA2 gene, there was no difference in their chances of dying from the disease whether they opted to have bilateral risk-reducing mastectomy or chose to have closer surveillance instead.

The study of 1,696 BRCA1 mutation carriers and 1,139 BRCA2 mutation carriers in The Netherlands is the first to prospectively follow healthy women who opted for either bilateral risk-reducing mastectomy or surveillance in order to compare their overall risk of dying from any cause and their risk of dying from breast cancer.

The women were selected from the national Hereditary Breast and Ovarian Cancer Netherlands (HEBON) database. They were healthy with no previous history of cancer, and had retained both breasts and ovaries at the time of the DNA diagnosis that detected the BRCA1/2 gene mutations. The women were followed from the time of their DNA diagnosis (the earliest was in January 1995) through to June 2017, or the time of their death or last follow-up appointment. During this time 38% (652) of the BRCA1 carriers and 32% (361) of the BRCA2 mutation carriers underwent bilateral risk-reducing mastectomy.

Findings

After an average follow-up time of approximately 9 to 11 years, there were 7 cases of breast cancer and 11 deaths (one due to breast cancer) among the BRCA1 mutations carriers who had bilateral risk-reducing mastectomy, while there were 269 breast cancer cases and 50 deaths (19 due to breast cancer) in the surveillance group. At the age of 65, overall survival among BRCA1 mutation carriers was 90% in the bilateral risk-reducing mastectomy group compared to 83% in the surveillance group. At the same age, breast cancer–specific survival was 99.6% in the bilateral risk-reducing mastectomy group compared to 93% for the surveillance group.

For BRCA2 mutation carriers, after an average follow-up time of approximately 9 to 10 years, there were no cases of breast cancer and two deaths (none due to breast cancer) in the bilateral risk-reducing mastectomy group, and 144 breast cancer cases and 32 deaths (7 due to breast cancer) in the surveillance group. However, at the age of 65, while overall survival was 95% for the bilateral risk-reducing mastectomy group compared to 88% for the surveillance group, breast cancer–specific survival was 100% for the bilateral risk-reducing mastectomy group compared to 98% for the surveillance group.

Annette Heemskerk-Gerritsen, PhD, a postdoctoral researcher at the Erasmus University Medical Centre in Rotterdam, The Netherlands, told the conference, “For BRCA1 mutation carriers, [bilateral risk-reducing mastectomy] not only drastically reduces the risk of developing breast cancer but, as a consequence, also improves breast cancer–specific survival when compared to surveillance. For BRCA2 mutation carriers, however, [bilateral risk-reducing mastectomy] seems to lead to similar breast cancer–specific survival as surveillance, despite the reduced breast cancer risk.”

Differences Between BRCA1 and BRCA2

She said the difference in the chances of dying from breast cancer between BRCA1 and BRCA2 mutation carriers supports the idea that these two mutations result in different types of tumors.

“We observed that BRCA2-associated breast cancers were diagnosed with more favorable characteristics than BRCA1-associated breast cancers. BRCA2-associated cancers were diagnosed at an older age, better differentiated, and were more likely to have receptors for the hormones estrogen and progesterone and for the human epidermal growth factor (HER2), suggesting that BRCA2 mutation carriers face a better prognosis at diagnosis than BRCA1 mutation carriers.”

The results of the study mean that women with BRCA2 gene mutation can choose between bilateral risk-reducing mastectomy or surveillance knowing that it makes little difference to whether or not they will die from breast cancer. However, they will still be at increased risk of developing the disease.

Dr. Heemskerk­-Gerritsen said, “For those BRCA2 mutation carriers who are struggling with the difficult choice between breast cancer surveillance and [bilateral risk-reducing mastectomy] because they wish to keep their breasts—and who are willing to face the risk of developing breast cancer and undergoing essential treatment after diagnosis—it might be a relief to know that ongoing intensive surveillance may be as good as [bilateral risk-reducing mastectomy] when it comes to breast cancer–specific survival. Our findings contribute to a more individualized counselling process regarding the difficult choice between [bilateral risk-reducing mastectomy] and surveillance based on the type of BRCA mutation.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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