Retrospective Analysis Confirms Poor Prognosis for Breast Cancer Patients With BRCA1 Mutations

Oncology & Biotech News, June 2013, Volume 7, Issue 6

Women with breast cancer who are carriers of BRCA1 mutations have increased mortality compared with noncarriers, according to a retrospective study carried out in the Netherlands.

Marjanka Schmidt, PhD

Women with breast cancer who are carriers of BRCA1 mutations have increased mortality compared with noncarriers, according to a retrospective study carried out in the Netherlands between 1970 and 2002, and reported at the 2013 AACR Annual Meeting. However, survival was not significantly different for BRCA2 carriers in this analysis.

“We have analyzed data from one of the largest, least biased, BRCA1- and 2-genotyped breast cancer cohorts. These findings were not surprising to us. We expected worse survival in mutation carriers, who have an enormously increased risk of developing breast cancer, including contralateral breast cancer,” said lead author Marjanka Schmidt, PhD, of Netherlands Cancer Institute in Amsterdam.

Schmidt commented that it is interesting that studies show that BRCA mutation carriers with ovarian cancer actually have improved survival compared with noncarriers.

Previous smaller studies in breast cancer patients showed overall worse survival for BRCA1/2 carriers, but those studies focused on Ashkenazi Jews, who typically carry only three of the hundreds of possible mutation variants. Schmidt and colleagues sought to determine whether these findings could be validated in the Dutch population, who would be likely to carry a broader spectrum of BRCA mutations.

The study included 5518 women diagnosed with breast cancer before the age of 50 at one of 10 clinics in the Netherlands; 3.6% were found to be BRCA1 mutation carriers and 1.2% were BRCA2 carriers. At a median follow-up of 11.3 years, overall survival (OS) rates were 1.2 times worse in BRCA1 carriers than in noncarriers, and the difference was statistically significant (P = .07); recurrence-free survival rate was 1.5 times worse in BRCA1 carriers, and the difference was also statistically significant (P = .004). A trend toward poorer survival was observed in BRCA2 carriers, but this result was not statistically significant.

Interestingly, 86% of patients who were non-BRCA mutation carriers, 81% of BRCA2 carriers, and 29% of BRCA1 carriers had estrogen receptor (ER)—positive tumors, which generally have a better prognosis than ER-negative tumors.

In a preliminary analysis, after adjusting for known tumor characteristics, the effect of BRCA1 status on survival remained strong but was somewhat attenuated. “So, part of the worse survival in BRCA1 mutation carriers may be related to tumor characteristics as well as mutation status,” Schmidt said.

The next step will be to assess survival in various subgroups of patients in this large retrospective dataset, including characteristics like ER status, progesterone receptor status, HER2 status, as well as luminal A and B types of basal-like breast cancer.

Schmidt said that BRCA carrier status and data from the subgroup analyses could be factored into decision making regarding the need for more-aggressive treatment.

Schmidt MMK, van den Broek AJ, Tollenaa Rob AEM, et al. Breast cancer survival of BRCA1/2 carriers compared to non-BRCA1/2 carriers in a large breast cancer cohort. Presented at: the AACR Annual Meeting 2013; April 6-10, 2013; Washington, DC. Abstract 1338.