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Article Type

Article

Abstract

Background: Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer represents an aggressive subtype of breast cancer historically associated with poor prognosis. The introduction of HER2-targeted therapies has significantly improved clinical outcomes; however, survival varies considerably among patients. Identifying prognostic factors that influence treatment response and survival is essential for optimizing patient management. This study aimed to evaluate clinical prognostic factors affecting survival outcomes in patients with HER2-positive metastatic breast cancer treated with targeted therapy in Spain. Methods: A retrospective multicenter cohort study was conducted across several oncology centers in Spain. The study included women aged ≥ 18 years with histologically confirmed HER2-positive metastatic breast cancer who received at least one line of HER2-targeted therapy between January 2014 and December 2022. Clinical data were extracted from institutional electronic medical records and oncology databases. Variables analyzed included demographic characteristics, hormone receptor status, metastatic site distribution, treatment patterns, and survival outcomes. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Prognostic factors were evaluated using univariate and multivariate Cox proportional hazards regression analyses. Results: A total of 168 patients were included in the study, with a median age of 55 years at diagnosis of metastatic disease. Hormone receptor–positive tumors were identified in 61.9% of patients. Visceral metastases were present in 66.7% of cases, and 17.3% of patients developed brain metastases. The median follow-up duration was 42 months. The median overall survival for the entire cohort was 48.6 months, while the median progression-free survival following first-line HER2-targeted therapy was 14.8 months. Multivariate analysis identified visceral metastases (HR 1.68; 95% CI 1.11–2.54) and brain metastases (HR 2.14; 95% CI 1.33–3.45) as independent predictors of poorer survival. Conversely, hormone receptor positivity (HR 0.72; 95% CI 0.51–0.96) and the use of dual HER2 blockade in the first-line setting (HR 0.64; 95% CI 0.44–0.91) were associated with improved survival outcomes. Conclusion: In this multicenter real-world study from Spain, several clinical factors significantly influenced survival in patients with HER2-positive metastatic breast cancer treated with targeted therapy. Hormone receptor positivity and the use of dual HER2 blockade were associated with improved outcomes, whereas visceral and brain metastases predicted poorer prognosis. These findings emphasize the importance of tumor biology and treatment strategy in determining survival and support the continued use of early intensive HER2-targeted therapy in metastatic disease.

Keywords

HER2-positive breast cancer, Metastatic breast cancer, Targeted therapy, Prognostic factors, Trastuzumab, Pertuzumab, Dual HER2 blockade

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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