# Histopathological and Clinical Features of HER2-Positive Breast Cancers across Hormone Receptor Subgroups: A Cross-Sectional Analysis

## TL;DR

This study compares clinicopathological features of HER2-positive breast cancers across hormone receptor subgroups, finding that the HER2-enriched subtype is more aggressive.

## Contribution

The study provides new insights into the distinct clinicopathological profiles of HER2-positive breast cancers based on hormone receptor status.

## Key findings

- The HER2-enriched subgroup (ER-/PR-/HER2+) is associated with older age and higher tumor grade.
- Triple-positive (ER+/PR+/HER2+) and HER2-enriched subgroups show significant differences in age and histological grade.
- HER2-enriched tumors exhibit a more aggressive phenotype with advanced nodal stage.

## Abstract

HER2-positive breast carcinomas are a heterogeneous group with various clinicopathological characteristics depending on hormone receptor (HR) status. This study aimed to analyze and compare the clinical and histopathological features of HER2-positive breast carcinomas across three subgroups: Group 1: Triple-positive (ER+/PR+/HER2+), Group 2:ER-positive only (ER+/PR-/HER2+), and Group 3: HER2-enriched (ER-/PR-/HER2+).

This was a single-institution, retrospective, cross-sectional study conducted over 42 months (January 2021–June 2024) at a tertiary care center comprising of 117 HER2-positive breast carcinoma cases. The demographic, clinical, and histopathological parameters were studied retrospectively. Statistical analysis was performed via SPSS Version 29.0, employing ANOVA and chi-square tests, with p < 0.05 considered significant.

Among 117 HER2-positive breast cancer patients, left and right breast involvement was nearly equal. Most were diagnosed via core biopsy (83.8%), with the upper outer quadrant most commonly affected (42.9%). Invasive breast carcinoma of no special type was the predominant subtype. The HER2-enriched group (Group 3) had the highest mean age (57.28 years;
p = 0.001) and the most Grade 3 tumors (36.1%;
p = 0.005). Although Group 2 (ER-positive) had the largest mean tumor size (4.31 cm), the difference was not statistically significant (
p = 0.143). Lymphovascular invasion, necrosis, Ductal carcinoma in situ (DCIS), and skin involvement showed no significant differences across groups. ANOVA showed significant variation in age and grade, and post-hoc analysis confirmed that Group 1 vs Group 3 differed significantly in both age (
p = 0.001) and grade (
p = 0.004).

HER2-positive breast carcinomas show variability by HR status. The HER2-enriched subtype is associated with older age, higher histological grade, and advanced nodal stage, suggesting a more aggressive phenotype. Recognizing these patterns aids in accurate prognostication and guiding individualized therapy.