Predictors of response to neoadjuvant chemo-immunotherapy in metaplastic triple-negative breast cancer

Metaplastic breast cancer (MpBC) treated with standard chemotherapy has low rates of complete pathological response (pCR)(2-23%). In this study, we evaluate the response to neoadjuvant chemo-immunotherapy (NACI) in early-stage MpBC. Thirty-two stage I-III MpBC patients treated with NACI (KEYNOTE-522 regimen) were prospectively enrolled in an institutional rare tumor program. All MpBC were triple negative; most were of chondromyxoid/matrix-producing (12/32, 38%). The majority had stage II (78%) tumors, 12/32 (37.5%) patients completed NACI, 11/32 (34%) progressed during NACI, and in the remaining 9, NACI was discontinued due to side effects. The pCR rate in the entire cohort was 22% (7/32) and it was statistically higher (5/8, 62%) among patients with high ( ≥ 60%) stromal tumor-infiltrating lymphocytes (sTILs) as compared to patients with < 60% sTILs (1/11, 9%). Most patients received adjuvant systemic therapy (capecitabine 16/32, pembrolizumab 20/32). At a median follow-up of 13 months, there were a total of 2 local recurrences, 10 distant recurrences, and 7 deaths. We demonstrated a modest pCR rate in MpBC with the addition of pembrolizumab (22%). Nonetheless, amongst patients with high sTILs, high pCR rates-comparable to those in the KEYNOTE-522 trial-were observed. These findings suggest that sTILs can be used to triage MpBC patients for NACI.