Genomic and Immune Profiling of a Patient With Triple-Negative Breast Cancer That Progressed During Neoadjuvant Chemotherapy Plus PD-L1 Blockade

Preliminary results from neoadjuvant trials combining immune checkpoint blockade (ICB) with standardof-care chemotherapy suggest high pathologic complete response rates that range between 50% and 80% in triple-negative breast cancer (TNBC). Adding atezolizumab to NAB-paclitaxel for first-line treatment of metastatic TNBC significantly improved response rate and progression-free survival compared with NABpaclitaxel alone, suggesting synergy between ICB and chemotherapy. However, not all patients respond to ICB, and a minority exhibit rapid progression of their disease. Patients who experience exceptionally favorable or unfavorable responses provide unique opportunities for studying disease biology and for identifying response markers. Progression during neoadjuvant chemotherapy is a rare event in TNBC. Here, we report results from the molecular analysis of a TNBC that rapidly progressed during neoadjuvant chemotherapy plus programmed death-ligand 1 (PDL1) blockade in a clinical trial Neoadjuvant MEDI4736 Concomitant With Weekly NAB-paclitaxel and Dosedense AC for Stage I-III Triple Negative Breast Cancer (ClinicalTrials.gov identifier: NCT02489448). Among the first 30 patients in this ongoing trial, no other participant experienced disease progression. We also hoped to identify potentially actionable genomic alterations or immunologic features.