Moderate immunohistochemical expression of her-2 (2) without her-2 gene amplification is a negative prognostic factor in early breast cancer

Valentina Rossi, Ivana Sarotto, Furio Maggiorotto, Paola Berchialla, Franziska Kubatzki, Nicoletta Tomasi, Stefania Redana, Rossella Martinello, Giorgio Valabrega, Massimo Aglietta, Riccardo Ponzone, Filippo Montemurro

Research output: Contribution to journalArticle

Abstract

Background. Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined "HER-2-" tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm. Methods. We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis. Results. Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2- by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2-/HER-2+ by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2- status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649. Conclusion. A HER-2 2-/HER-2- status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/ HER-2- status are ideal candidates for studies testing this hypothesis.

Original languageEnglish
Pages (from-to)1418-1425
Number of pages8
JournalThe oncologist
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Breast cancer
  • Fluorescence in situ hybridization
  • Her-2
  • Immunohistochemistry
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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