e12589 Background: Pembrolizumab combined with chemotherapy improves pathological complete response (pCR) in early-stage triple-negative breast cancer (TNBC). However, real-world predictors of response and the reliability of imaging biomarkers remain unclear. We evaluated clinical, biological, and imaging factors associated with pCR in a real-world TNBC cohort treated with neoadjuvant pembrolizumab. Methods: This retrospective study included 35 patients with stage II–III TNBC treated with neoadjuvant chemotherapy plus pembrolizumab. Post-neoadjuvant PET-CT was performed before surgery. Associations between pCR (ypT0/is ypN0) and PET-CT response, HER2-low status, germline homologous recombination repair (HRR) mutations, carboplatin completion, menopausal status, and pembrolizumab dose were analyzed using Fisher’s exact test. Results: The overall pCR rate was 62.8%, comparable to KEYNOTE-522. Complete metabolic response (CMR) on PET-CT was strongly associated with pCR; all patients achieving pCR demonstrated CMR, and no pCR occurred among patients with partial response or stable disease (p = 0.003). PET-CT showed 100% sensitivity and negative predictive value for pCR. HER2-low tumors had lower pCR rates than HER2-0 tumors (45% vs. 70%), despite similar CMR rates, suggesting a discordance between imaging and pathological responses. Germline HRR mutation status did not significantly impact pCR (63.5% vs 62.5%). Carboplatin completion was associated with numerically higher pCR rates (71.5% vs 50%). Pembrolizumab dose and menopausal status were not associated with pCR. Immune-related adverse events were consistent with known safety profiles. Conclusions: In this real-world TNBC cohort, PET-CT CMR strongly predicted pCR after pembrolizumab-based neoadjuvant therapy. However, HER2-low tumors demonstrated reduced pathological response despite favorable metabolic imaging, indicating that tumor biology may modify the predictive value of PET-CT. These findings may refine response assessment and identify subgroups that could benefit from post-neoadjuvant escalation strategies.
Vijayaraghavan et al. (Thu,) studied this question.