Subtyping of male breast cancer by PAM50 and immunohistochemistry: a pilot study of a consecutive Danish cohort

APMIS. 2020 Sep;128(9):523-530. doi: 10.1111/apm.13068.

Abstract

Male breast cancer (MBC) is a rare disease that is still to be fully understood. In female breast cancer, molecular subtyping by gene expression has proven its significance. In this study, we characterize a consecutive cohort of MBC patients surgically treated from 1997 to 2017, identified at our institution (N = 37), and report the association between molecular subtypes found by a surrogate panel of immunohistochemical (IHC) markers, and the PAM50 signature, as well as risk of recurrence score and overall survival for the different subtypes. PAM50 subtypes were determined using the nCounter FLEX system instrument and software. The distribution of molecular subtypes according to the PAM50 signature was as follows: 56% luminal B, 39% luminal A, and 5% basal-like. None of the tumors were HER2-enriched. Using IHC surrogate markers, we found 80% luminal B-like, 15% luminal A-like, and 5% basal-like. None were HER2-positive (non-luminal). We found a strong statistical association between subtypes found by PAM50 signature and the IHC surrogate markers (p < 0.001). Furthermore, we found luminal A tumors to be smaller in size compared to luminal B tumors (p = 0.04). Patients with luminal A subtype tumors had the lowest ROR scores with a mean of 39, whereas patients with luminal B subtype tumors had a mean ROR score of 69. Significant worse overall survival for luminal B tumors compared to luminal A tumors was seen (p = 0.02). Male breast cancer seems to be a mainly luminal disease, with luminal B being the most frequent subtype. Further studies are needed to ensure correct therapeutic strategies for this select group of patients.

Keywords: Genomic subtyping; histopathology; male breast cancer; molecular pathology; surgical pathology.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms, Male / genetics
  • Breast Neoplasms, Male / metabolism
  • Breast Neoplasms, Male / pathology*
  • Cohort Studies
  • Denmark
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Pilot Projects
  • Recurrence
  • Risk

Substances

  • Biomarkers, Tumor