ESMO 2024: highlights in breast cancer

Several clinically relevant abstracts in the field of breast cancer (BC) were presented during the 2024 congress of the European Society for Medical Oncology (ESMO). Updates from the phase 3 NATALEE trial supported the role of cyclin-dependent kinase (CDK) 4/6 inhibitors in early-stage hormone-receptor (HR)-positive/HER2-negative breast cancer with intermediate to high risk of recurrence, while an update of KEYNOTE-522 reported an overall survival (OS) benefit with pembrolizumab in early-stage triple-negative disease. In HER2-positive early-stage BC, the phase 2 WSG-TP-II trial reported excellent long-term outcomes with de-escalated neoadjuvant chemotherapy combined with trastuzumab and pertuzumab. A retrospective analysis of endocrine treatment strategies in the pivotal HERA trial emphasized the importance of ovarian function suppression (OFS) in premenopausal patients with HR-positive/HER2-positive disease, even in the presence of HER2-directed treatments. Antibody–drug conjugates (ADCs) remain a key focus of scientific interest. Results from DESTINY-Breast12 support the use of trastuzumab deruxtecan (T-DXd) in metastatic HER2-positive BC patients with active brain metastases (BM), showing high response rates and prolonged disease control in this phase 3b/4 study. The single-arm phase 2 ICARUS-Breast01 trial demonstrated promising results of the HER3-directed ADC patritumab deruxtecan in pretreated patients with metastatic luminal disease. Biological differences between HR-positive/HER2-positive and HR-negative/HER2-positive BC are evident, and DETECT V questions the need for chemotherapy while corroborating previous data supporting the role of CDK 4/6 inhibitors in patients with HR-positive/HER2-positive disease. In patients with metastatic triple-negative breast cancer (TNBC), bispecific antibodies co-targeting PD‑1 or PD-L1 and VEGF showed promising results. Despite sound clinical rationale, inhibition of the PI3K/AKT/mTOR pathway in metastatic TNBC remained unsuccessful in the CAPItello-290 trial.