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A substantial minority of early breast cancer (EBC) patients relapse despite their tumors achieving pathologic complete response (pCR) after neoadjuvant therapy. We compared gene expression (BC360; nCounter ®  platform; NanoString) between primary tumors of patients with post-pCR relapse ( N  = 14) with: (i) matched recurrent tumors from same patient (intraindividual analysis); and (ii) primary tumors from matched controls with pCR and no relapse ( N  = 41; interindividual analysis). Intraindividual analysis showed lower estrogen receptor signaling signature expression in recurrent tumors versus primaries (logFC = −0.595;  P  = 0.022). Recurrent tumors in patients with distant metastases also exhibited reduced expression of immune-related expression parameters. In interindividual analyses, primary tumor major histocompatibility complex class II expression was lower versus controls in patients with any relapse (logFC = −0.819;  P  = 0.030) or distant relapse (logFC = −1.151;  P  = 0.013). Primaries with later distant relapse also had greater homologous recombination deficiency than controls (logFC = 0.649;  P  = 0.026). Although no associations remained statistically significant following adjustment for false discovery rate, our results show that transcriptomic analyses have potential for prognostic value and may help in selecting optimal treatment regimens for EBC at risk of relapse and warrant further investigation.

Gene signatures in patients with early breast cancer and relapse despite pathologic complete response