Molecular characterization of patients with pathologic complete response or early failure after neoadjuvant chemotherapy for locally advanced breast cancer using next generation sequencing and nCounter assay

Oncotarget. 2015 Sep 15;6(27):24499-510. doi: 10.18632/oncotarget.4119.

Abstract

Neoadjuvant chemotherapy (NAC) has the added advantage of increasing breast conservation rates with equivalent survival outcomes compared with adjuvant chemotherapy. A subset of breast cancer patients who received NAC experienced early failure (EF) during the course of therapy or within a short period after curative breast surgery. In contrast, patients with pathological complete response (pCR) were reported to have markedly favorable outcomes. This study was performed to identify actionable mutation(s) and to explain refractoriness and responsiveness to NAC. Included in this analysis were 76 patients among 397 with locally advanced breast cancer for whom a preoperative fresh-frozen paraffin-embedded tumor block was available for next-generation sequencing using AmpliSeq. The incidence of missense mutations in KRAS was much higher in patients with EF than in other groups (p < 0.01). In contrast, polymorphisms of the cMET gene were found in patients with pCR exclusively (p < 0.01).

Keywords: breast cancer; neoadjvant chemotherapy; pathologic complete response; refractory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Base Sequence
  • Breast / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Disease-Free Survival
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Mutation, Missense / genetics
  • Neoadjuvant Therapy*
  • Polymorphism, Single Nucleotide / genetics
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Sequence Analysis, DNA
  • Treatment Failure

Substances

  • KRAS protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins p21(ras)