The clinical value of HER-2 overexpression and PIK3CA mutations in the older breast cancer population: a FOCUS study analysis

Breast Cancer Res Treat. 2016 Apr;156(2):361-70. doi: 10.1007/s10549-016-3734-y. Epub 2016 Mar 11.

Abstract

Studies to confirm the effect of acknowledged prognostic markers in older breast cancer patients are scarce. The aim of this study was to evaluate the prognostic value of HER-2 overexpression and PIK3CA mutations in older breast cancer patients. Female breast cancer patients aged 65 years or older, diagnosed between 1997 and 2004 in a geographical region in The Netherlands, with an invasive, non-metastatic tumour and tumour material available, were included in the study. The primary endpoint was relapse-free period and secondary endpoint was relative survival. Determinants were immunochemical HER-2 scores (0/1+, 2+ or 3+) and PIK3CA as a binary measure. Overall, 1698 patients were included, and 103 had a HER-2 score of 3+. HER-2 overexpression was associated with a higher recurrence risk (5 years recurrence risk 34 % vs. 12 %, adjusted p = 0.005), and a worse relative survival (10 years relative survival 48 % vs. 84 % for HER-2 negative; p = 0.004). PIK3CA mutations had no significant prognostic effect. We showed, in older breast cancer patients, that HER-2 overexpression was significantly associated with a worse outcome, but PIK3CA mutations had no prognostic effect. These results imply that older patients with HER-2 overexpressing breast cancer might benefit from additional targeted anti-HER-2 therapy.

Keywords: Anti-HER2 therapy; Breast cancer; Competing risk; Epidemiology; Geriatric oncology; HER-2; PIK3CA; Prognostic markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Class I Phosphatidylinositol 3-Kinases
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation*
  • Netherlands
  • Phosphatidylinositol 3-Kinases / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Survival Analysis
  • Up-Regulation*

Substances

  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2