Chromosome 17 polysomy without human epidermal growth factor receptor 2 amplification does not predict response to lapatinib plus paclitaxel compared with paclitaxel in metastatic breast cancer

Leona Downey, Robert B. Livingston, Maria Koehler, Michael Arbushites, Lisa Williams, Angela Santiago, Roberta Guzman, Ivonne Villalobos, Angelo Di Leo, Michael F. Press

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Purpose: It has been suggested that a subgroup of human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with chromosome 17 (Chr-17) polysomy benefit from HER2-directed therapy. This hypothesis was examined using the data from a phase III trial that randomized patients with HER2-negative or HER2-untested metastatic breast cancer to first-line therapy with paclitaxel along with either lapatinib or placebo. Experimental Design: HER2 expression level by immunohistochemistry, fluorescence in situ hybridization (FISH), and mean HER2 ratio of Chr-17 values were determined centrally using archival tissue. Polysomy means of 2.0 and 2.2 served as thresholds. Results: Of 580 patients on the original trial, 406 were HER2 negative by FISH. Progression-free survival (PFS) data were available for 405 patients, of whom 44 (11%) met the definition of polysomy (Chr-17 ≥2.2, FISH negative for HER2). Median PFS in the polysomy group was 20.9 and 24.4 weeks for paclitaxel plus lapatinib and paclitaxel plus placebo, respectively. In the nonpolysomy group, median PFS was 24.6 and 23.1 weeks for paclitaxel plus lapatinib and paclitaxel plus placebo, respectively. Log-rank testing showed no treatment advantage for either group. Similar results were found using a Chr-17 polysomy cutoff of 2.0. Response rates in the polysomy group were 17% for paclitaxel plus lapatinib and 10% for paclitaxel plus placebo. In the nonpolysomy group, response rates were 32% for paclitaxel plus lapatinib and 25% for paclitaxel plus placebo. Neither comparison was statistically significant. Conclusion: This analysis could not confirm the hypothesis that Chr-17 polysomy in HER2-nonamplified patients improved chemotherapy outcome when lapatinib is added as a HER2-targeted treatment.

Original languageEnglish (US)
Pages (from-to)1281-1288
Number of pages8
JournalClinical Cancer Research
Volume16
Issue number4
DOIs
StatePublished - Feb 15 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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