Therapeutic strategies in male breast cancer: clinical implications of chromosome 17 gene alterations and molecular subtypes

Breast. 2013 Dec;22(6):1066-71. doi: 10.1016/j.breast.2013.08.008. Epub 2013 Sep 27.

Abstract

Male breast cancer (MBC) is a rare disease. To date, therapy is mainly based on studies and clinical experiences with breast cancer in women. Only little is known about molecular typing of MBC, particularly with regard to potential biological predictors for adjuvant therapy. In female breast cancer tumors with chromosome 17 centromere (CEP17) duplication, HER2 and/or Topoisomerase II alpha (Topo II-α) gene alterations have been suggested to be associated with poor prognosis and increased sensitivity to anthracycline-containing regimens. In a well characterized cohort of 96 primary invasive MBC, we studied CEP17, HER2 and Topo II-α alterations by fluorescence in-situ hybridization (FISH), and expression of hormone receptors (HR), HER2 and Ki67 by immunohistochemistry to define molecular subtypes. Tumor characteristics and follow-up data were available and correlated with molecular findings. HER2 amplification and Topo II-α amplification/deletion were exceptionally rare in MBC (6.3% and 3.1%, respectively). CEP17 polysomy were found in 9.4% of tumors. HER2, Topo II-α and CEP17 gene alterations were not correlated to patients outcome. 96.9% of our cases were HR positive. Triple negative tumors were found in only 3.1% of the cases. In nodal negative tumors luminal A subtypes were significantly associated with better overall survival. Our results provide evidence for a predominant male breast cancer phenotype, characterized by HR expression and a lack of HER2/Topo II-α alterations and CEP17 duplicates. Therefore, the impact of anthracycline sensitivity linked to HER2/Topo II-α alterations as found in female breast cancer has low clinical significance for this specific male breast cancer phenotype.

Keywords: CEP 17; ER; HR; MBC; Male breast cancer; PR; Prognosis; Subtypes; Topo II-α; Topoisomerase II-α; chromosome 17 centromere; estrogen receptor; hormone receptor; male breast cancer; n.s.; not significant; progesterone receptor; topoisomerase II-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anthracyclines / therapeutic use
  • Antigens, Neoplasm / genetics*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms, Male / chemistry*
  • Breast Neoplasms, Male / drug therapy
  • Breast Neoplasms, Male / genetics*
  • Carcinoma / chemistry*
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • Centromere / genetics
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA Topoisomerases, Type II / genetics*
  • DNA-Binding Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis
  • Male
  • Phenotype
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics*
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Retrospective Studies
  • Survival Rate

Substances

  • Anthracyclines
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II