Functional assays revealed that BRCA2 deficiency significantly increased sensitivity to the poly (ADP-ribose) polymerase inhibitor olaparib, whereas tamoxifen sensitivity remained unchanged.<h4>Conclusion</h4>This study presents the first detailed characterization of ER signaling alterations in ER-positive/HER2-negative breast cancers with germline BRCA2 PVs, offering insights for the development of targeted therapeutic strategies for this patient population. Here, ESR1 is linked to breast carcinoma.