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.