HER2-positive grade 1 invasive carcinomas of the breast

Histopathology. 2025 Jan;86(2):278-284. doi: 10.1111/his.15315. Epub 2024 Sep 11.

Abstract

Aims: The American Society of Clinical Oncology and College of American Pathologists HER2-guidelines recommend repeat testing for most grade 1 mammary carcinomas that are HER2-positive in the core biopsy. This study aimed to assess the value of repeat HER2-testing and the histological features of HER2-positive grade 1 carcinomas.

Methods and results: A case-series of HER2-results of grade 1 carcinomas was conducted of patients with no pre-operative systemic treatment over a 5-year period. HER2-positive carcinomas had histological review. Twelve HER2-positive carcinomas were initially reported as grade 1. On review, two were reclassified as grade 2. The remaining 10 carcinomas represented 2% of the 508 grade 1 carcinomas. Eight HER2-positive grade 1 carcinomas from other years were also studied. HER2-positive carcinomas more often had marked nuclear pleomorphism (50 versus 6%) and were more often oestrogen receptor-negative (17 versus 0.8%) and progesterone receptor-negative (28 versus 8%) compared with HER2-negative grade 1 carcinomas. Six carcinomas that were HER2 3+ in the core biopsy were also 3+ on repeat assessment. Five of seven carcinomas that were 2+ amplified in the core biopsy were also HER2-positive in the excision.

Conclusions: HER2-positive grade 1 carcinomas are uncommon, and more often have marked nuclear pleomorphism and lack oestrogen receptor and progesterone receptor expression compared with HER2-negative grade 1 carcinomas. A HER2-poitive result in the core biopsy was confirmed in 11 of 13 tumours that had repeat testing.

Keywords: HER2; breast; carcinoma; histological grade; in‐situ hybridisation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Erb-b2 Receptor Tyrosine Kinases* / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading

Substances

  • Erb-b2 Receptor Tyrosine Kinases
  • Biomarkers, Tumor
  • ERBB2 protein, human