Disparities in Targeted Therapy Access and Survival by Molecular Subtype in Breast Cancer: Evidence from Yemen

Abstract

Background: Breast cancer management has evolved toward precision medicine based on molecular subtypes. In low-resource settings like Yemen, access to targeted therapies is limited, potentially exacerbating survival disparities. This study examines treatment patterns and survival outcomes across molecular subtypes in a large Yemeni cohort from a conflict-affected setting. Methods: A retrospective analysis of 1,167 breast cancer patients at the National Oncology Center in Aden, Yemen (2017-2024) was conducted. Patients were classified into four molecular subtypes: Luminal A-like (HR+/HER2-), Luminal B-like (HR+/HER2+), HER2-enriched (HR-/HER2+), and Triple-Negative (TNBC). Treatment patterns (surgery, chemotherapy, endocrine therapy, anti-HER2 therapy) and mortality at last follow-up were compared across subtypes using chi-square tests and multivariate logistic regression. Due to 41.9% loss to follow-up, survival analysis was restricted to 678 patients with documented outcomes. Results: The cohort comprised 611 (52.4%) Luminal A-like, 168 (14.4%) Luminal B-like, 139 (11.9%) HER2-enriched, and 284 (24.3%) TNBC cases. Significant disparities in treatment access were observed: only (66.2%) of eligible HR+ patients received endocrine therapy; only (61.2%) of HER2+ patients received anti-HER2 therapy. TNBC patients had the highest rate of mastectomy (78.2%) and chemotherapy (98.2%). Mortality at last follow-up varied significantly by subtype: Luminal A-like (61.7% alive), Luminal B-like (54.8% alive), HER2-enriched (48.9% alive), and TNBC (42.6% alive; p<0.001). On multivariate analysis, TNBC subtype (OR 2.8, 95% CI 1.6-4.9) and lack of minimum subtype-specific systemic therapy (OR 3.1, 95% CI 1.8-5.4) were independent predictors of mortality. Median follow-up duration was 24 months (range 1-84 months). Conclusion: Profound disparities exist in access to precision therapy for breast cancer in Yemen, particularly affecting HER2+ and TNBC patients. The survival disadvantage of TNBC patients persists even in this late-presenting cohort, highlighting the urgent need for equitable access to essential cancer medicines and clinical trial inclusion for aggressive subtypes in conflict settings. These findings provide actionable evidence for global oncology policy and humanitarian cancer care strategies.