The 2024 San Antonio Breast Cancer Symposium (SABCS) featured groundbreaking research poised to reshape breast cancer care. Clinicians presented data on novel antibody-drug conjugates (ADCs), biomarkers, surgical interventions, and radiotherapy modalities, offering potential improvements in patient outcomes across diverse populations.
Neoadjuvant Patritumab Deruxtecan Shows Promise
Findings from the phase 2 SOLTI VALENTINE trial (NCT05569811) revealed that neoadjuvant patritumab deruxtecan (HER3-DXd), with or without letrozole, maintained responses while reducing toxicities compared to multi-agent chemotherapy. The study, led by Mafalda Oliveira, MD, PhD, suggests HER3-DXd's efficacy in early breast cancer, particularly in high-risk, hormone receptor (HR)-positive, HER2-negative cases. HER3-DXd monotherapy achieved a pathologic complete response (pCR) rate of 4.0% (95% CI, 0.5%-13.7%) and an objective response rate (ORR) of 70.0% (95% CI, 55.4%-82.1%). Grade 3 or higher treatment-related adverse effects (TRAEs) were notably lower with HER3-DXd alone (14.0%) and in combination with letrozole (14.6%) compared to chemotherapy (45.8%).
Long-Term Olaparib Efficacy in BRCA-Mutated Breast Cancer
A six-year pre-specified analysis of the phase 3 OlympiA trial (NCT02032823) demonstrated the sustained efficacy of olaparib versus placebo in HER2-negative, high-risk breast cancer patients with BRCA1/2 mutations. Olaparib improved invasive disease-free survival (iDFS; HR, 0.65; 95% CI, 0.53-0.78) and distant disease-free survival (DDFS; HR, 0.65; 95% CI, 0.53-0.81) at six years.
T-DXd Improves Outcomes in Metastatic Breast Cancer
The phase 3 DESTINY-Breast06 trial (NCT04494425) showcased that fam-trastuzumab deruxtecan-nxki (T-DXd) improved progression-free survival (PFS) compared to physician’s choice of therapy (TPC) in HR-positive, HER2-low metastatic breast cancer, irrespective of endocrine resistance and time to progression (TTP). T-DXd demonstrated PFS improvements in patients with a TTP of less than 6 months (HR, 0.69; 95% CI, 0.43-1.12) or more than 12 months on frontline therapy (HR, 0.67; 95% CI, 0.51-0.88). Furthermore, T-DXd prolonged PFS in patients with primary (HR, 0.57; 95% CI, 0.42-0.77) and secondary endocrine resistance (HR, 0.68; 95% CI, 0.55-0.84).
Surgical Interventions and Monitoring Strategies
Research also highlighted the impact of surgical interventions and monitoring strategies. Risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO) improved efficacy outcomes in BRCA-mutated patients aged 40 or younger. A meta-analysis indicated that immediate surgery significantly reduced local recurrence in elderly breast cancer patients compared to delayed surgery (RR, 0.25; 95% CI, 0.19-0.34; P <.00001 for node-negative disease with immediate surgery plus tamoxifen). The COMET trial (NCT02926911) found that active monitoring was non-inferior to guideline-concordant care (GCC) for low-risk DCIS, with ipsilateral invasive cancer rates of 4.2% in the active monitoring arm versus 5.9% in the GCC arm at 2 years.
