Expression Patterns and Clinical Relevance of HSP70 and Metallothionein in Triple-Negative and Luminal A Breast Cancer: A Croatian Cohort Study

Metallothioneins (MTs) and heat shock protein 70 (HSP70) are key regulators of cellular stress response and metal homeostasis and play important roles in tumor biology. The aim of this study was to examine their expression patterns and potential prognostic significance in different molecular subtypes of breast cancer (BC), with special emphasis on triple-negative breast cancer (TNBC) and the Luminal A subtype, compared with benign breast lesions (fibroadenomas). A total of 90 tissue samples were included, and the expression of MTs in the cytoplasm and nucleus and HSP70 in the nucleus of tumor cells was analyzed immunohistochemically and correlated with clinicopathological features and treatment outcomes. Distinct expression patterns of HSP70 and MTs were observed between malignant and benign samples, as well as among the analyzed molecular subtypes of BC, suggesting their involvement in cellular adaptive mechanisms associated with malignant transformation. TNBC was characterized by less favorable clinicopathological features compared to the Luminal A subtype, including higher histological grade, increased proliferative activity, and a higher incidence of recurrence and metastatic disease. Survival analyses confirmed a worse outcome for patients with TNBC, while HSP70 and MTs expression did not show independent prognostic value in multivariate models. In conclusion, although HSP70 and MTs play important biological roles in the cellular response to stress and tumor adaptation, their expression in this study does not represent an independent prognostic indicator of clinical outcome. Nevertheless, the observed expression patterns provide insight into the complex mechanisms of tumor adaptation and emphasize the need for integrative approaches in BC biomarker research.