Tampere University of Technology

TUTCRIS Research Portal

Very high quantitative tumor HER2 content and outcome in early breast cancer

Research output: Contribution to journalArticleScientificpeer-review

Details

Original languageEnglish
Pages (from-to)2007-2013
Number of pages7
JournalANNALS OF ONCOLOGY
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 2011
Publication typeA1 Journal article-refereed

Abstract

Background: It is unknown how a very high tumor total HER2 (human epidermal growth factor receptor-2) content (H2T) influences outcome in early breast cancer treated with adjuvant trastuzumab plus chemotherapy. Patients and methods: H2T was measured using a novel quantitative assay (HERmark®) from formalin-fixed tumor tissue of 899 women who participated in the FinHer trial (ISRCTN76560285). In a chromogenic in situ hybridization (CISH) test, 197 (21.9%) patients had HER2-positive cancer and were randomly assigned to receive trastuzumab or control. Results: Cancer H2T levels varied 1808-fold. High H2T levels were correlated with a positive HER2 status by CISH (P <0.0001). A nonlinear association was present between H2T and the hazard of distant recurrence in a subpopulation treatment effect pattern plot analysis in CISH-positive disease. Patients with very high H2T (defined by ≥ 22-fold the median of HER2-negative cancers; 13% of CISH-positive cancers) did not benefit from adjuvant trastuzumab [hazard ratio (HR) 1.23; 95% confidence interval (CI) 0.33-4.62; P = 0.75], whereas the rest of the patients with HER2-positive disease by CISH (87%) did benefit (HR 0.52; 95% CI 0.28-1.00; P = 0.050). Conclusion: Patients with HER2-positive breast cancer with very high tumor HER2 content may benefit less from adjuvant trastuzumab compared with those whose cancer has more moderate HER2 content.

ASJC Scopus subject areas

Keywords

  • Adjuvant therapy, Breast cancer, Human epidermal growth factor receptor-2, In situ hybridization, Prognosis, Trastuzumab