Daily highlights – 3

General Session 3 of the 2025 San Antonio Breast Cancer Symposium presented important data spanning cancer prevention, screening, fertility preservation, and new systemic therapies for hormone receptor–positive breast cancer.

A matched prospective analysis in patients with germline BRCA1 or BRCA2 mutations evaluated the safety of hormone replacement therapy after natural or surgical menopause. Estrogen-only hormone therapy appeared to have a protective effect, while combined estrogen–progesterone therapy showed similar risks regardless of hormone use.

The Italian PREFER prospective cohort study demonstrated that controlled ovarian stimulation for oocyte cryopreservation did not adversely affect oncologic outcomes, supporting fertility preservation strategies in young patients with breast cancer.¹

The WISDOM-1 trial showed that personalised, risk-based breast cancer screening was superior to standard screening. Risk stratification incorporated breast density, demographic factors, and genomic profiling. Risk-based screening resulted in more stage I and fewer stage II cancers detected, without increasing total cancer detection. Despite limitations related to opportunistic screening, results were encouraging and may support future implementation of personalized screening strategies.²

Updated efficacy results from the EMBER-3 trial were presented in advanced ER+/HER2- breast cancer. Imlunestrant monotherapy showed sustained PFS benefit in patients with ESR1 mutations, with consistent trends toward improved OS and delayed time to chemotherapy. Imlunestrant is now FDA-approved for this population, with expected EMA approval.

The combination of imlunestrant and abemaciclib significantly improved PFS compared with imlunestrant alone, regardless of ESR1 or PI3K mutation status and prior CDK4/6 inhibitor use. OS data remain immature, and regulatory approval for the combination is pending. Safety findings were consistent with previous reports. Interpretation of EMBER-3 results is limited by trial design features, including incomplete prior CDK4/6 inhibitor exposure and comparator selection, which affect assessment of clinical benefit.³

The evERA phase III trial evaluated giredestrant plus everolimus versus standard endocrine therapy plus everolimus after progression on a CDK4/6 inhibitor. The combination significantly improved PFS in both ESR1-mutant and overall populations, with benefit primarily driven by ESR1-mutant tumours. Response rates and duration of response also favoured the experimental arm. Toxicity was largely attributable to everolimus, with overall safety manageable. These results may lead to regulatory approval, although tolerability concerns and pending OS data remain relevant.

The expanding therapeutic landscape beyond CDK4/6 inhibition presents challenges for treatment selection and reimbursement, which will significantly influence clinical practice.