BRCA 1/2 Status in Triple-negative Breast Cancer May Affect Responsiveness to Carboplatin

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Patients with triple-negative breast cancer without BRCA1 and BRCA2 germline mutations may benefit from the addition of carboplatin to a chemotherapy regimen.
Patients with triple-negative breast cancer without BRCA1 and BRCA2 germline mutations may benefit from the addition of carboplatin to a chemotherapy regimen.

Patients with triple-negative breast cancer (TNBC) without BRCA1 and BRCA2 germline mutations may benefit from the addition of carboplatin to a chemotherapy regimen, according to a study published in JAMA Oncology.1

The GeparSixto Trial (ClinicalTrials.gov Identifier: NCT01426880) demonstrated that patients with TNBC have higher rates of pathological complete response (pCR) if carboplatin is added to the nonstandard regimen of anthracycline, taxane, and bevacizumab.

In this secondary analysis of the GeparSixto Trial, researchers analyzed cancer family history and DNA samples to determine BRCA1 and BRCA2 mutation status.  Of the 291 enrolled patients with TNBC, 50 patients were BRCA1- and BRCA2-positive. The primary outcomes measured were disease-free survival after treatment and the proportion of patients who achieved pCR.

Overall, the pCR rate was 56.8% in the carboplatin arm vs 41.4% in the non-carboplatin arm (odds ratio [OR], 1.87; 95% CI, 1.17-2.97; P = .009).

Patients with BRCA1 and BRCA2 mutations in the non-carboplatin arm had a pCR rate of 66.7% vs 36.4% for those without (OR, 3.50; 95% CI, 1.39-8.84; P = .008). Patients who were BRCA1 and BRCA2 mutation-positive did not have any increases in pCR with the addition of carboplatin (66.7% vs 65.4%).

Patients without BRCA1 and BRCA2 saw increased response rates with the addition of carboplatin. The carboplatin arm had a pCR rate of 55% vs 36.4% for those in the non-carboplatin arm (OR, 2.14; 95% CI, 1.28-3.58; P = .004).

Disease-free survival rates were increased in patients without BRCA1 and BRCA2 mutations when carboplatin was added (85%; 95% CI, 77.0%-90.8%) vs without carboplatin (73%; 95% CI, 64.1%-80.8%), (hazard ratio, 0.53; 95% CI, 0.29-0.96; P = .04).

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The authors concluded that “additional prospective studies stratified by BRCA1 and BRCA2 mutation status are needed to elucidate the effect of carboplatin in polychemotherapy regimens.”

Reference

  1. Hahnen E, Lederder B, Huake J, et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer. JAMA Oncol. 2017 Jul 13. doi: 10.1001/jamaoncol.2017.1007 [Epub ahead of print]

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