Predictors of Pathologic Complete Response with Neoadjuvant Chemo-Immunotherapy in Early-Stage Triple-Negative Breast Cancer.

Background: The combination of pembrolizumab with neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) improves pathologic complete response (pCR) rates and event-free survival. Yet it is unclear which patients benefit most from the addition of immunotherapy. This study aims to identify predictive factors for pCR in patients with TNBC receiving chemo-immunotherapy (chemo-IO).

Patients and methods: This single-institution retrospective analysis included 283 consecutive patients with TNBC treated with neoadjuvant chemo-IO from 1 June 2021 to 20 January 2023. The primary outcome was overall pCR; secondary outcomes were breast pCR and nodal pCR. Univariate and multivariable logistic regression models assessed for characteristics associated with overall, breast, or nodal pCR.

Results: Most patients presented with cT2 (71%) cN0 (54%) disease. The overall pCR rate was 57%, breast pCR was 58%, and axillary pCR was 67% among biopsy-proven cN+ patients. Race, pathogenic BRCA mutations, backbone chemotherapy regimen, immune-related adverse events, and disruptions in immunotherapy were not associated with pCR. Univariate associations with overall pCR were younger age (p = 0.04), lower clinical T stage (p = 0.01), ductal histology (p < 0.001), poor differentiation (p < 0.001), and unifocality (p < 0.001). Breast and axillary pCR had similar associations. Nodal pCR also had univariate associations with normal body mass index (BMI) (p = 0.04) and absence of lymphovascular invasion (LVI) (p = 0.04). On multivariable analyses, ductal histology and unifocality remained independently associated with overall and breast pCR.

Conclusions: This analysis showed few clinical variables to be independently associated with pCR after neoadjuvant chemo-IO for TNBC. Thus, predicting chemo-IO response to personalize treatment and minimize morbidity may instead lie in ongoing basic and translational research to assess for useful biomarkers.