BRCAness predicts resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy

Clin Breast Cancer. 2015 Feb;15(1):80-5. doi: 10.1016/j.clbc.2014.08.003. Epub 2014 Sep 28.

Abstract

Background: To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.

Patients and methods: We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information.

Results: We obtained 45 CNB and 60 surgical specimens from the 73 patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14 had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P = .03) and for TNBC (50% vs. 100%, P = .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8% vs. 14.3%, P = .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P = .002) and in TNBC cases (P = .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P = .049).

Conclusion: Identifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue.

Keywords: Multiplex ligation-dependent probe amplification; Platinum salts; Predictive marker; Prognostic marker; Taxane resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation
  • Neoadjuvant Therapy
  • Prognosis
  • Retrospective Studies
  • Taxoids / administration & dosage*
  • Triple Negative Breast Neoplasms / congenital
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Taxoids