Healthy women who carried the BRCA1 mutation had reduced risk for developing breast cancer and mortality if they underwent bilateral risk-reducing mastectomy, according to results of a prospective study presented at the European Breast Cancer Conference.
However, carriers of the BRCA2 mutation had similar likelihood of mortality regardless of whether they underwent bilateral risk-reducing mastectomy or surveillance alone.
“Counseling regarding the sometimes difficult choice between bilateral risk-reducing mastectomy and breast cancer surveillance should be different for BRCA1 and BRCA2 mutation carriers,” Annette Heemskerk-Gerritsen, PhD, postdoctoral researcher at Erasmus University Medical Center in the Netherlands, told HemOnc Today. “For BRCA1 mutation carriers, bilateral risk-reducing mastectomy not only reduces the risk [for] developing breast cancer, but also the risk for dying of the disease. For BRCA2 mutation carriers, bilateral risk-reducing mastectomy does reduce the risk for developing breast cancer but, when it comes to dying of breast cancer, surveillance may be as effective as bilateral risk-reducing mastectomy.”
Heemskerk-Gerritsen and colleagues evaluated records of 2,835 women enrolled in the national Hereditary Breast and Ovarian Cancer Netherlands database to compare the overall risk for mortality from any cause with risk for mortality from breast cancer between BRCA1 and BRCA2 carriers.
Of the women, 1,696 carried the BRCA1 mutation and 1,139 carried the BRCA2 mutation.
At the time of BRCA1/BRCA2 mutation detection, all women were healthy, had no prior history of cancer and had both breasts and ovaries. Researchers followed women through June 2017, last follow-up appointment or death.
During follow-up, 652 BRCA1 carriers and 361 BRCA2 carriers underwent bilateral risk-reducing mastectomy.
Among BRCA1 carriers, 269 breast cancer cases and 50 deaths occurred over follow-up of 9.5 years. Among BRCA2 carriers, 144 breast cancer cases and 37 deaths occurred over follow-up of 8.5 years. Researchers attributed 19 deaths in the BRCA1 group and seven in the BRCA2 group to breast cancer.
After a mean follow-up of 10.8 years, seven breast cancer cases and 11 deaths occurred among BRCA1 carriers who underwent bilateral risk-reducing mastectomy.
After a mean follow-up of 9.5 years, two deaths — not attributed to breast cancer — and no incidence of breast cancer occurred among BRCA2 carriers who underwent bilateral risk-reducing mastectomy.
The HR for OS in favor or bilateral risk-reducing mastectomy over surveillance was 0.55 (95% CI, 0.28-1.07) for BRCA1 carriers and 0.32 (95% CI, 0.08-1.38) for BRCA2 carriers.
OS at age 65 years among BRCA1 carriers was 83% for the surveillance group compared with 90% for the mastectomy group. OS at age 65 years among BRCA2 carriers was 88% for the surveillance group compared with 95% for the mastectomy group.
Multivariable Cox models showed the HR for breast cancer-specific survival with bilateral risk-reducing mastectomy was 0.07 (95% CI, 0.01-0.55) for BRCA1 carriers.
Breast cancer-specific survival appeared higher among the mastectomy group than the surveillance group at age 65 years (99.6% vs 93%) among BRCA1 carriers.
Breast cancer-specific survival was 98% for BRCA2 carriers in the surveillance group and 100% in the mastectomy group, which indicated that the risk for mortality from breast cancer was low among this patient population, with no difference between the groups.
“We think this is most probably due to the more favorable characteristics of BRCA2-associated breast cancers — which are more often diagnosed at older age, more often in situ, better differentiated, and less often showing a triple-negative phenotype,” Heemskerk-Gerritsen said. “Therefore, the chances of surviving breast cancer when diagnosed under surveillance may be better for BRCA2 mutation carriers than for BRCA1 mutation carriers.”
A patient should know whether their risk for dying of breast cancer is significantly different if they undergo preventive mastectomy rather than just surveillance. This may impact decision-making, Heemskerk-Gerritsen noted.
“For those who are in doubt of having their healthy breasts removed, it may be important to know that their risks of dying from breast cancer are not that different whether they opt for preventive mastectomy or stay under surveillance,” Heemskerk-Gerritsen said. “When remaining under surveillance, though, they will still be at risk [for] developing breast cancer and undergoing necessary treatment after diagnosis.” – by Melinda Stevens
Heemskerk-Gerritsen A, et al. Abstract 134. Presented at: European Breast Cancer Conference; March 18-20, 2018; Barcelona, Spain.
Disclosures: The authors report no relevant financial disclosures.