The residual tumor autophagy marker LC3B serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy

Abstract

Purpose: This study sought to investigate the prognostic value of the autophagy marker microtubule- associated protein chain 3B (LC3B) in patients with residual tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer (LABC). Patients and Methods: The expression of LC3B in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens from 229 patients diagnosed with histologically proven invasive breast cancer. All patients underwent NCT followed by mastectomy and were considered nonpathologic complete responders (non-pCR) after a pathologic evaluation. The prognostic value of various clinicopathologic factors was evaluated. Results: The LC3B density was similar between the peripheral and central area of the tumors (P = 0.328) but was significantly lower in the extratumoral area (P < 0.001 and P < 0.001, respectively). Furthermore, LC3B density, which correlated with Beclin-1 expression, Ki-67 index, and breast cancer subtype, served as an independent prognostic factor for both relapse-free survival (RFS; P = 0.012) and overall survival (OS; P = 0.008); the prognostic value of LC3B was most significant in triple-negative patients. Using a combination of LC3B expression and the status of residual involved lymph nodes, the patients were classified into four groups with different risks of relapse and death (P < 0.001 for RFS and P = 0.003 for OS). Conclusion: LC3B can be used as a prognostic marker in patients with non-pCR after NCT for breast cancer, which highlights the importance of autophagy in the biologic behavior of chemoresistant cancer cells. Furthermore, evaluating and targeting autophagy in the neoadjuvant setting may help prevent disease relapse in patients with non-pCR. © 2013 American Association for Cancer Research.