PLoS ONE 2015-01-01

Clinical Implications of iNOS Levels in Triple-Negative Breast Cancer Responding to Neoadjuvant Chemotherapy.

Zining Jin, Wenqian Wang, Nan Jiang, Lei Zhang, Yiming Li, Xiaoyin Xu, Shouliang Cai, Liang Wei, Xuhong Liu, Guanglei Chen, Yizhen Zhou, Cheng Liu, Zhan Li, Feng Jin, Bo Chen

Index: PLoS ONE 10 , e0130286, (2015)

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Abstract

Triple-negative breast cancer is a high-risk breast cancer with poor survival rate. To date, there is a lack of targeted therapy for this type of cancer. One unique phenomenon is that inflammatory breast cancer is frequently triple negative. However, it is still ambiguous how inflammation influences triple-negative breast cancer growth and responding to chemotherapy. Herein, we investigated the levels of inflammation-associated enzyme, iNOS, in 20 triple-negative breast cancer patients' tumors, and examined its correlation with patients' responses to platinum-based neoadjuvant chemotherapy. Our studies showed that triple-negative breast cancer patients with attenuated iNOS levels in tumor cells after treatment showed better responses to platinum-based neoadjuvant chemotherapy than other triple-negative breast cancer patients. Our further in vitro studies confirmed that induction of proper levels of NO increased the resistance to cisplatin in triple-negative MDA-MB-231 cells. Our data suggest that aberrant high level of iNOS/NO are associated with less effectiveness of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer. Therefore, we propose to monitor iNOS levels as a new predictor for triple-negative breast cancer patient's response to platinum-based neoadjuvant chemotherapy. Moreover, iNOS/NO is considered as a potential target for combination therapy with platinum drugs for triple-negative breast cancer.