Clinicopathological and molecular characteristics associated with pathological complete response in neoadjuvant immunotherapy for breast cancer

Background In breast cancer, immune checkpoint inhibitor (ICI)-based neoadjuvant therapy has been approved for clinical practice since 2021. Nonetheless, the predictive values of routinely collected clinicopathological and molecular characteristics in neoadjuvant immunotherapy remain unknown. Methods We searched EMBASE and MEDLINE databases for randomized controlled trials (RCTs) comparing ICI-based neoadjuvant therapy with conventional treatment. The primary outcome was pathological complete response (pCR). The odds ratio (OR) and its 95% confidence intervals (CIs) were calculated. This meta-analysis was registered in PROSPERO (CRD420261307112). Results Here, with 5674 patients enrolled in 12 RCTs, our study revealed ICI-based neoadjuvant therapy was associated with significantly increased pCRs (OR, 1.59; 95% CI, 1.32-1.90; P < 0.001). Notably, neoadjuvant immunotherapy did not demonstrate a statistically significant improvement of pCRs in patients with HER2+ tumors (OR, 1.17; 95% CI, 0.92-1.49; P = 0.23). Moreover, the interactions between ICI-based neoadjuvant therapy and nodal status ( P Interaction < 0.001) or stromal tumor-infiltrating lymphocyte (sTIL, P Interaction = 0.05) were statistically meaningful. More pCRs were observed in patients with nodal-positive (OR, 1.89; 95% CI, 1.56-2.28; P < 0.001) or high-density sTIL tumors (OR, 2.89; 95% CI, 1.49-5.61; P < 0.001), but not in women with nodal-negative (OR, 1.05; 95% CI, 0.80-1.39; P = 0.71) or low-density sTIL tumors (OR, 1.26; 95% CI, 0.73-2.17; P = 0.41). There was insufficient evidence to support other characteristics, including race, age, PD-L1 expression, clinical stage, hormone receptor (HR) status, menopausal status, Eastern Cooperative Oncology Group (ECOG) performance status, and T stage, as predictive biomarkers to guide patient selection for neoadjuvant immunotherapy in breast cancer. Conclusion Neoadjuvant immunotherapy was associated with favorable outcomes in breast cancer. However, for patients with HER2+, nodal-negative, or low-density sTIL tumors, clinicians need to carefully balance efficacy, safety, and patient preferences to deliver individualized treatment. Further randomized trials with long-term outcomes are needed to confirm the predictive values of these biomarkers. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261307112 , identifier PROSPERO CRD420261307112.