Women with Triple-Negative Breast Cancer Very Likely to Carry BRCA1 Gene

Phoebe Starr

February 2013, Vol 4, No 2 - Personalized Medicine


San Antonio, TX—Triple-negative breast cancer (TNBC) was strongly associated with BRCA1 status, but not with BRCA2 status, in a large study of medically insured women. The study showed that the number of patients with BRCA mutations with a TNBC profile is statistically significant.

Findings from a poster presented at the 2012 Annual CTRC-AACR San Antonio Breast Cancer Symposium suggest that patients with TNBC should be referred to a genetics counselor for further evaluation and possible genetic testing.

Women with TNBC are thought to be more likely to be BRCA carriers, but it is controversial whether newly diagnosed women with TNBC should be referred for genetic counseling. The recommendation for genetic counseling in this group of patients rests only on studies with small numbers of BRCA carriers. Thus, there is no clear guideline, explained lead author Reina Haque, PhD, MPH, a research scientist at the Department of Research and Development, Kaiser Permanente Southern California, Pasadena.

The study was conducted by investigators at Kaiser Permanente, a large health plan with >3.5 million diverse members at >200 medical centers throughout southern California. The study was based on a retrospective cohort of 2105 women with breast cancer who were tested for BRCA mutations between 1997 and 2011. The BRCA results were reported in the health plan’s clinical genetics registry. Of the 2105 patients with breast cancer, 249 were carriers of a BRCA mutation; there were 143 BRCA1 carriers and 106 BRCA2 carriers.

Data linkages were performed for all patients with the National Cancer Institute-SEER (Surveillance, Epidemiology and End Results)–affiliated tumor registry; estrogen receptor (ER), progesterone receptor (PR), and HER2 statuses were captured and were assessed by immunohistochemical or fluorescence in situ hybridization techniques. Patients were classified into the 2 main biologic subtypes of TNBC (ER-negative, PR-negative, HER2-negative) and non-TNBC (luminal A, luminal B, and HER2-enriched). The association between TNBC and non-TNBC and BRCA1 or BRCA2 mutation status was examined.

The TNBC subtype was strongly correlated with BRCA status (P <.001). Women with TNBC tumors were 5 times more likely to be BRCA carriers than women with non-TNBC tumors (odds ratio [OR], 5.6; 95% confidence interval [CI], 4.1-7.5).

The association between TNBC and BRCA1 was more robust (OR, 12.2; 95% CI, 8.3-17.9), and was unchanged after adjusting for age, stage at diagnosis, and race or ethnicity. TNBC was not associated with BRCA2 status (OR, 1.6; 95% CI, 0.9-2.7).

These findings in a large sample of women suggest that patients with TNBC should be referred for further evaluation and for genetic testing, because results may inform treatment choice.