Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).
Patrick D Rädler, Brooke M Felsheim, Aranzazu Fernandez-Martinez et al.
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In 30 seconds
This phase II randomized controlled trial evaluated residual disease (RD) in 340 pretreatment and 70 posttreatment samples from patients with triple-negative breast cancer (TNBC). The study found that patients with a basal-like genomic subtype in RD had poor survival outcomes, indicating that RD biology differs from pretreatment tumors. Notably, the immune microenvironment in RD was characterized as immune-cold.
Key findings
- Patients with basal-like RD had poor survival outcomes compared to other subtypes.
- RD specimens showed further lymphocyte depletion and lower MHC class I expression.
- Preclinical models treated with sacituzumab govitecan or trastuzumab deruxtecan showed marked antitumor responses.
Why it matters
Understanding the differences in RD biology compared to pretreatment tumors can help identify high-risk patients and inform treatment strategies. The findings suggest that specific therapies may be needed for patients with basal-like RD to improve outcomes.