Evaluation of HER2-Low breast carcinoma in metastatic settings: a cytological approach to proliferation and survival.

Abstract

Introduction: Human epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by HER2 immunohistochemistry scores of 1+ or 2+ without gene amplification, represents a unique subgroup with emerging therapeutic implications. Limited data describe the behavior of HER2-low tumors, particularly in metastatic settings. This study evaluated the frequency of HER2-low expression, Ki-67 proliferation index, and survival outcomes across HER2 subtypes in metastatic breast carcinoma using cytology specimens.

Methods: A 3-year retrospective analysis identified 43 patients with metastatic breast carcinoma diagnosed via fine-needle aspiration or exfoliative cytology. HER2, ER, PR, and Ki-67 status were determined by immunohistochemistry, with equivocal HER2 cases assessed by in situ hybridization. Survival outcomes were estimated using the Kaplan-Meier method, with Cox regression identifying predictors of survival.

Results: Among 43 cases, 31 (70.5%) were HER2-low, 6 (13.6%) HER2-positive, and 6 (13.6%) HER2-zero. HER2 discordance between primary and metastatic lesions occurred in 19%, mainly involving transitions to HER2-low status. Hormone receptor positivity was more frequent in HER2-low tumors (71%) than HER2-zero tumors (33%) (P < 0.001). Mean Ki-67 was highest in HER2-low (45%) versus HER2-negative (34%) and HER2-positive (33%) cases (P = 0.549). Median survival was 13 months for HER2-low and 5 months for HER2-negative patients; survival differences were not significant (P = 0.225). Younger age (HR = 0.240, P = 0.048) and hormone receptor positivity (HR = 0.273, P = 0.011) were significant predictors of survival.

Conclusion: HER2-low expression is prevalent in metastatic breast carcinoma with a unique hormone receptor profile. Findings highlight the need for reassessment of HER2 status in metastatic settings, with potential therapeutic implications.