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SABCS 2022 | HRD, RB-loss gene sig, intrinsic subtype and response to neoadjuvant treatment in HR+/HER2- early BC

Gaia Griguolo, MD, Istituto Oncologico Veneto, Padua, Italy, provides an overview of a correlative analysis of two Phase II trial to assess the relationship between homologous recombination deficiency (HRD), RB-loss gene signatures, intrinsic subtype and response to neoadjuvant treatment in HR-positive, HER2- negative early breast cancer. The two Phase II trials were GIADA (NCT04659551), a multicentric neoadjuvant phase II trial that treated premenopausal patients with Luminal B-like HR-positive, HER2-negative breast cancer with a combination of chemotherapy, immunotherapy and endocrine treatment, and LETLOB (NCT00422903) that randomized postmenopausal women with clinical stage II-IIIA HR-positive, HER2 negative breast cancer to neoadjuvant letrozole plus lapatinib or letrozole plus placebo for 6 months. Intrinsic subtype was assigned using a research-based PAM50 subtype predictor. A published HRD signature and a signature of RB loss (RBsig), previously reported to potentially predict resistance to CDK4/6 inhibitors in HR+/HER2- BC were computed. Higher levels of HRD signature was found to be associated with a more basal-like phenotype by the PAM50 signature and associated with higher sensitivity to neoadjuvant chemotherapy with high pathological complete response (pCR) rates and lower sensitivity to endocrine neoadjuvant treatment. These observations may help to personalize systemic treatment in patients with HR-positive, HER2-negative early and advanced breast cancer. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2022 in San Antonio, TX.

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