Abstract
Objective: Breast cancer exhibits biological heterogeneity that varies across age groups and influences treatment decisions. This study aimed to evaluate age-related differences in biomarker profiles, surrogate molecular subtypes, and treatment patterns in a single-center real-world breast cancer cohort.
Material and Methods: This retrospective cohort study included 1,124 patients with invasive breast cancer diagnosed or followed between January 2020 and June 2025. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and Ki-67 proliferation index were analyzed. Tumors were classified into surrogate molecular subtypes according to the St. Gallen and European Society for Medical Oncology recommendations. Biomarker distributions, molecular subtypes, and treatment modalities were compared across age groups. Multivariable logistic regression analyses were performed to identify independent predictors of HER2 positivity and triple-negative breast cancer (TNBC).
Results: Significant age-related differences were observed in ER status, HER2 status, Ki-67 index, and surrogate molecular subtype distribution. Younger patients more frequently exhibited ER negativity, HER2 positivity, high proliferative activity, and aggressive molecular subtypes, whereas older patients predominantly presented with hormone receptor-positive, lower-proliferation tumors. Neoadjuvant therapy was more frequently used in younger patients, while treatment de-escalation was observed in older age groups. The HER2-low phenotype was identified in 18.4% of the cohort. Age, PR status, Ki-67 level, and histological grade were independent predictors of HER2 positivity and TNBC.
Conclusion: Age-related biological differences in breast cancer are closely aligned with real-world treatment decisions. Treatment strategies are primarily guided by tumor biology rather than chronological age alone.