Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer

Matthew J. Ellis, Li Lin, Robert Crowder, Yu Tao, Jeremy Hoog, Jacqueline Snider, Sherri Davies, Katherine Deschryver, Dean B. Evans, Jutta Steinseifer, Raj Bandaru, Weihua Liu, Humphrey Gardner, Vladimir Semiglazov, Mark Watson, Kelly Hunt, John Olson, José Baselga

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Mutations in the alpha catalytic subunit of phosphoinositol-3-kinase (PIK3CA) occur in ∼30% of ER positive breast cancers. We therefore sought to determine the impact of PIK3CA mutation on response to neoadjuvant endocrine therapy. Exons 9 (helical domain) and 20 (kinase domain-KD) mutations in PIK3CA were determined samples from four neoadjuvant endocrine therapy trials. Interactions with clinical, pathological, and biomarker response parameters were examined. A weak negative interaction between PIK3CA mutation status and clinical response to neoadjuvant endocrine treatment was detected (N = 235 P ≤ 0.05), but not with treatment-induced changes in Ki67-based proliferation index (N = 418). Despite these findings, PIK3CA KD mutation was a favorable prognostic factor for relapse-free survival (RFS log-rank P = 0.02) in the P024 trial (N = 153). The favorable prognostic effect was maintained in a multivariable analysis (N = 125) that included the preoperative endocrine prognostic index, an approach to predicting RFS based on postneoadjuvant endocrine therapy pathological stage, ER, and Ki67 levels (HR for no PIK3CA KD mutation, 14, CI 1.9-105 P = 0.01). PIK3CA mutation status did not strongly interact with neoadjuvant endocrine therapy responsiveness in estrogen receptor-positive breast cancer. Nonetheless, as with other recent studies, a favorable interaction between PIK3CA KD mutation and prognosis was detected. The mechanism for the favorable prognostic impact of PIK3CA mutation status therefore remains unexplained.

Original languageEnglish
Pages (from-to)379-390
Number of pages12
JournalBreast Cancer Research and Treatment
Volume119
Issue number2
DOIs
StatePublished - Jan 2010

Keywords

  • Estrogen receptor-positive breast cancer
  • Neoadjuvant endocrine therapy
  • Phosphatidyl-inositol-3-kinase
  • Prognosis
  • Somatic mutation

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