Evaluation of tolerability and efficacy of incorporating carboplatin in neoadjuvant anthracycline and taxane based therapy in a BRCA1 enriched triple-negative breast cancer cohort

Tal Sella*, Einav Nili Gal Yam, Keren Levanon, Tal Shapira Rotenberg, Moran Gadot, Iryna Kuchuk, Rinat Bernstein Molho, Amit Itai, Tami Mekel Modiano, Raya Gold, Bella Kaufman, Shani Paluch Shimon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The addition of carboplatin (Cb) to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) has been demonstrated to improve pathologic complete response (pCR) at the expense of increased toxicity. We aimed to evaluate the effectiveness and tolerability of dose-dense anthracycline & cyclophosphamide (ddAC) followed by weekly paclitaxel (wT) in combination with weekly Cb. Methods: Retrospective data was collected on patients with clinical stage I-III TNBC treated with neoadjuvant ddAC-wTCb (four cycles of ddA 60 mg/m2 and ddC 600 mg/m2 every 2 weeks followed by 12 cycles of wT 80 mg/m2 with Cb AUC 1.5). Indices of tolerability and pCR were evaluated and compared to a historical cohort (n = 76) treated with ddAC-T. A secondary objective was to evaluate the rates of pCR by BRCA status. Results: For 43 eligible patients, mean age was 41.5 years, 51% had clinical stage II disease, 81.4% were clinically node positive and 32.6% carried a deleterious BRCA1 mutation. Only 35% completed all scheduled doses of chemotherapy. Grade 3/4 neutropenia was observed in 42.5% of patients. Overall pCR was 51.2%; 44.8% in BRCA wild-type compared to 64.3% in BRCA–associated TNBC (p = 0.232). pCR rates with ddAC-wTCb were similar to historic institutional rates with ddAC-T (51.2% vs. 51.3%, p = 0.987) and were comparable when stratified by BRCA status. In pooled multivariate analysis, only BRCA status (HR 4.00, 95%CI 1.65–9.75, p = 0.002) was significantly associated with pCR. Conclusion: Neoadjuvant ddAC-wTCb is less tolerable in clinical practice compared to most clinical trials, with a pCR comparable to historic rates using non-platinum regimen. The role of Cb in neoadjuvant chemotherapy for BRCA mutated TNBC remains uncertain.

Original languageEnglish
Pages (from-to)141-146
Number of pages6
JournalBreast
Volume40
DOIs
StatePublished - Aug 2018

Keywords

  • BRCA
  • Carboplatin
  • Neoadjuvant chemotherapy
  • Triple negative breast cancer

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