Landscape of Germline Pathogenic Variants in Luminal Breast Cancer from an Under-Represented Southeast Asian Populations

Germline pathogenic variants influence breast cancer risk and clinical behavior, yet data from Indonesian populations remain scarce. In this pilot cross-sectional study, 31 newly diagnosed Indonesian women with luminal A or luminal B breast cancer underwent germline testing using a 113-gene hereditary cancer panel, with variants classified according to ACMG criteria and correlated with clinicopathological features. Pathogenic or likely pathogenic variants were identified in 9 of 31 patients (29.0%), most frequently involving BRCA2, PALB2, and RECQL4. A significantly higher frequency of pathogenic/likely pathogenic variants was observed among patients with mixed invasive histology (3/3) compared with those with invasive carcinoma of no special type (6/27; p = 0.019), and a positive first-degree family history of breast cancer was also associated with pathogenic/likely pathogenic variant status (p = 0.022). This study provides the first description of germline pathogenic variants in Indonesian luminal breast cancer and suggests that mixed invasive histology and first-degree family cancer history may represent enrichment signals for hereditary predisposition, warranting validation in larger cohorts.