Journal
CLINICAL CANCER RESEARCH
Volume 19, Issue 24, Pages 6853-6862Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-13-1617
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Funding
- Multidiscipline Comprehensive Treatment Cooperation Group Foundation of Fudan University Cancer Hospital, Shanghai, China [DXK200801]
- Key Clinical Program of the Ministry of Health [2010-2012]
- Shanghai United Developing Technology Project of Municipal Hospitals [SHDC12010116]
- National Natural Science Foundation of China [30971143, 30972936, 81001169]
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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 non-pathologic 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. (C)2013 AACR.
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