Platinum salts in the treatment of BRCA-associated breast cancer: A true targeted chemotherapy?

Research output: Contribution to journalReview article

Abstract

Germline pathogenic mutations in breast cancer (BC) susceptibility genes (gBRCA1/2) are the most frequent inherited alterations in BC and are involved in the homologous recombination pathway, the principal mechanism of DNA double strand break repair. Platinum salts which act as DNA cross-linking agents are therefore more likely to be active in BRCA-deficient tumors. Women with gBRCA-associated tumors, particularly with triple negative BC, receiving neoadjuvant platinum containing regimens achieved higher pCR rates as compared to wild-type BC. However in two large randomized trials the addition of carboplatin significantly increased pCR rate only in wild-type tumors. On the contrary, the randomized TNT trial showed a significant benefit for carboplatin vs docetaxel in terms of response rate and PFS specifically in patients with advanced gBRCA -associated tumors. Biomarkers of sensitivity to DNA damaging agents beyond gBRCA mutations predicting activity of platinum salts have been proposed and should be validated prospectively.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalCritical Reviews in Oncology/Hematology
Volume135
DOIs
Publication statusPublished - Mar 2019

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Keywords

  • Antineoplastic Agents/therapeutic use
  • BRCA1 Protein/genetics
  • BRCA2 Protein/genetics
  • Breast Neoplasms/drug therapy
  • Carboplatin/therapeutic use
  • Cisplatin/therapeutic use
  • DNA Repair/genetics
  • Female
  • Germ-Line Mutation
  • Humans
  • Mutation

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