Heterogeneity of Hormone Receptors and HER2 in Breast Cancer Cutaneous Metastases: An Institutional Experience

Cutaneous metastases are an uncommon but clinically relevant manifestation of breast cancer (BC), often indicating advanced disease and biological progression. Temporal heterogeneity between primary tumors and metastatic lesions, particularly involving hormone receptors (HRs) and HER2 status, may influence prognosis and treatment decisions. We retrospectively analyzed BC patients with cutaneous metastases diagnosed at a tertiary care center between 2015 and 2024. Clinical data, histopathological features, and immunohistochemical profiles of estrogen receptor (ER), progesterone receptor (PgR), and HER2 were evaluated in paired primary tumors and cutaneous metastatic lesions under uniform pre-analytic and analytic conditions. Receptor discordance and survival outcomes were assessed. Among 660 patients with metastatic BC, 28 (4.2%) developed cutaneous metastases. Median age at diagnosis was 63 years, with chest wall as the most frequent site of skin involvement. HR-positive/HER2-negative tumors were predominant, while triple-negative breast cancer accounted for 19.4% of cases and was associated with a shorter disease course and earlier cutaneous metastatic spread. Receptor discordance occurred in 18.2% for ER, 36.4% for PgR and 41.4% for HER2, mainly involving transitions to or from HER2-low status. After skin involvement, prognosis remained poor. Cutaneous BC metastases show marked receptor heterogeneity, reflecting dynamic tumor evolution. These findings support re-biopsy and biomarker reassessment to guide personalized treatment in metastatic BC.