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Association of Germline Variant Status and Response to Neoadjuvant Chemotherapy in High-Risk Early Breast Cancer


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In a study of the GeparOcto trial population reported in JAMA Oncology, Pohl-Rescigno et al found that presence of germline BRCA1/2 variants was associated with increased rates of complete pathologic response (pCR) to neoadjuvant chemotherapy in women with high-risk early breast cancer, and that a nonplatinum regimen produced a high pCR rate in patients with BRCA1/2-mutated triple-negative breast cancer.

“Effective chemotherapy for BRCA1/2-mutated triple-negative breast cancer 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 [HER2]-negative, hormone receptor–positive [breast cancer] suggests that germline BRCA1/2 testing should be considered prior to treatment start.”
— Pohl-Rescigno et al

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Study Details

The trial compared two neoadjuvant regimens: sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) vs weekly paclitaxel and nonpegylated liposomal doxorubicin (PM) in patients with different biological breast cancer subtypes. Patients with triple-negative breast cancer randomly assigned to the PM group also received carboplatin (PMCb). In the primary analysis, no difference in pCR rates was observed between treatment groups.

The current retrospective biomarker study involved genetic analysis for variants in BRCA1/2 and 16 other predisposition genes in 914 of 945 women from the trial.

Key Findings

Overall, higher pCR rates were observed in patients with BRCA1/2 variants vs patients without such variants (60.4% vs 46.7%; odds ratio [OR] = 1.74, P = .01). Overall, variants in non-BRCA1/2 predisposition genes were not associated with response.

Patients with triple-negative breast cancer with BRCA1/2 variants exhibited the highest pCR rates. Among patients with triple-negative breast cancer, positive BRCA1/2 variant status was associated with significantly higher pCR rates in both the PMCb group (74.3% vs 47.0% without BRCA1/2 variant; OR = 3.26, P = .005) and in the iddEPC group (64.7% vs 45.0%; OR = 2.24, P = .04).

Positive BRCA1/2 variant status was associated with a higher pCR rate in patients with HER2-negative, hormone receptor–positive disease vs negative variant status (31.8% vs 11.9%; OR = 3.44, P = .02).

The investigators concluded, “Effective chemotherapy for BRCA1/2-mutated triple-negative breast cancer 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 [HER2]-negative, hormone receptor–positive [breast cancer] suggests that germline BRCA1/2 testing should be considered prior to treatment start.”

Eric Hahnen, PhD, of University Hospital Cologne, is the corresponding author for the JAMA Oncology article.

Disclosure: The GeparOcto study was supported by Roche, Amgen, Teva Pharmaceutical Industries, and Vifor Pharma. Support for research and genetic analyses was provided by the Koeln Fortune Program, Faculty of Medicine, University of Cologne. For full disclosures of the study authors, visit jamanetwork.com.

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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