Daily highlights – 1

General Session 1 at the San Antonio Breast Cancer Symposium 2025 presented several important studies, including potentially practice-changing results across early and metastatic breast cancer.

The lidERA trial reported the first Phase III data on giredestrant, a SERD and full ER antagonist, in the adjuvant setting. Giredestrant was compared with standard endocrine therapy in over 4,000 patients with ER-positive, HER2-negative early breast cancer and medium- or high-risk features. At a median follow-up of 32 months, giredestrant significantly improved IDFS compared with standard endocrine therapy, with a hazard ratio of 0.70. Improvements were also observed in distant recurrence-free survival, and early trends suggested a possible OS benefit. The safety profile was comparable to that of standard endocrine therapy, with fewer discontinuations and fewer arthralgia-related treatment interruptions. Bradycardia was observed, but was mostly low-grade and asymptomatic. These results position SERDs as a potential new option in the upfront adjuvant endocrine setting in patients with medium or high-risk features. ¹

The HER2CLIMB-05 trial evaluated maintenance tucatinib after first-line THP in HER2+ metastatic breast cancer. Tucatinib added to trastuzumab and pertuzumab significantly improved PFS compared with HP alone, with consistent benefit across subgroups. The greatest benefit was observed in hormone receptor-negative disease and in patients with baseline brain metastases, where CNS progression-free survival was doubled. Toxicities were manageable, with diarrhoea and transaminase elevations being the most frequent.

In contrast, the ASCENT-07 trial was negative. Sacituzumab govitecan did not improve PFS compared with physician’s-choice chemotherapy in HR+/ HER2- metastatic breast cancer when used before any chemotherapy. Although investigator-assessed PFS and OS trends slightly favoured sacituzumab govitecan, the primary endpoint was not met, confirming that its role remains after prior chemotherapy exposure.

Long-term follow-up from the ALTTO trial showed that aromatase inhibitors were superior to tamoxifen in HR+/HER2+ early breast cancer, particularly in premenopausal patients. AI use was associated with a significant improvement in 10-year disease-free survival.

Several translational studies were also highlighted. ctDNA analyses from the PHERGain trial showed that pre-surgery ctDNA positivity was associated with worse outcomes , whereas ctDNA clearance during neoadjuvant therapy was associated with improved prognosis. ⁵ Tumour-infiltrating lymphocytes (TILs) have been confirmed as prognostic and predictive biomarkers in HER2-positive disease, particularly in ER-positive tumours.⁶ Advanced AI-based spatial analysis of TILs further improved prognostic discrimination.⁷ Finally, integrating genomic and transcriptomic data enhanced the prognostic performance of Oncotype DX in the TAILORx cohort.⁸

Overall, the session highlighted major advances in endocrine therapy, HER2-positive disease management, and biomarker-driven risk stratification, with several findings likely to influence clinical practice.