Do Breast Cancer Treatment Outcomes Vary Based on Germline Variant Status?

A new study evaluated the effectiveness of breast cancer treatment based on germline variant status.

“The GeparOcto randomized clinical trial compared the efficacy of 2 neoadjuvant breast cancer (BC) treatment regimens: sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) vs weekly paclitaxel and nonpegylated liposomal doxorubicin (PM) in patients with different biological BC subtypes. Patients with triple-negative BC (TNBC) randomized to the PM arm received additional carboplatin (PMCb). Overall, no difference in pathologic complete response (pCR) rates was observed between study arms. It remained elusive whether the germline variant status of BRCA1/2 and further BC predisposition genes are associated with treatment outcome,” the researchers explained. The present study sought to answer that question.

This was a retrospective, secondary analysis of the GeparOcto study, which was a multicenter, prospective, randomized clinical trial that took place from December 2014 through June 2016. The researchers conducted genetic analyses to evaluate variants in BRCA1/2 and 16 other breast cancer predisposition genes in 914 of 945 women at the Center for Familial Breast and Ovarian Cancer, Cologne, Germany, from August 2017 through December 2018. The main outcome measure was the proportion of patients who achieve pCR following neoadjuvant treatment based on germline variant status.

BRCA1/2 Variants May Affect Treatment Outcomes

The mean age at breast cancer diagnosis of the 914 women included in this study sample was 48 (range, 21 to 76) years. Patients who had BRCA1/2 variants had higher pCR rates compared to patients without BRCA1/2 variants (60.4% vs. 46.7%; odds ratio [OR]=1.74; 95% confidence interval [CI], 1.13 to 2.68; P=0.01). No association was observed between variants in non-BRCA1/2 breast cancer predisposition genes and therapy response. Triple-negative breast cancer patients who had BRCA1/2 variants attained the highest pCR rates. In analyses of triple-negative breast cancer patients, a correlation was observed between positive BRCA1/2 variant status, compared to non-BRCA1/2 variant status, and therapy response, in the PMCb group (74.3% vs. 47.0%; OR=3.26; 95% CI, 1.44 to 7.39; P=0.005) as well as the iddEPC group (64.7% vs. 45.0%; OR=2.24; 95% CI, 1.04 to 4.84; P=0.04). In patients with ERBB2-negative, hormone receptor–positive disease, a relationship was observed between positive BRCA1/2 variant status, compared to non-BRCA1/2 variant status, and higher pCR rates (31.8% vs. 11.9%; OR=3.44; 95% CI, 1.22 to 9.72; P=0.02).

The study authors, whose research appeared in JAMA Oncology, concluded, “Effective chemotherapy for BRCA1/2-mutated TNBC is commonly suggested to be platinum based. With a pCR rate of 64.7%, iddEPC may also be effective in these patients, though further prospective studies are needed. The elevated pCR rate in BRCA1/2-mutated ERBB2-negative, hormone receptor–positive BC suggests that germline BRCA1/2 testing should be considered prior to treatment start.”