A combination of Nottingham prognostic index and IHC4 score predicts pathological complete response of neoadjuvant chemotherapy in estrogen receptor positive breast cancer
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Weige Tan1,2,*, Wei Luo1,*, Weijuan Jia1, Gehao Liang1, Xinhua Xie3, Wenbo Zheng2, Erwei Song1,4, Fengxi Su1, Chang Gong1
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
2Department of Breast Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
3Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
4Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University, Guangzhou, China
*These authors have contributed equally to this work
Chang Gong, email: [email protected]
Fengxi Su, email: [email protected]
Keywords: breast cancer, pathologic complete response, neoadjuvant chemotherapy, Nottingham prognostic index, IHC4
Received: July 13, 2016 Accepted: November 07, 2016 Published: November 24, 2016
Pathologic complete response (pCR) prediction after neoadjuvant chemotherapy (NAC) is important for clinical decision-making in breast cancer. This study investigated the predictive value of Nottingham prognostic index (NPI), Immunohistochemical four (IHC4) score and a new predictive index combined with them in estrogen-positive (ER+) breast cancer following NAC. We retrospectively gathered clinical data of 739 ER+ breast cancer patients who received NAC from two cancer centers. We developed a new predictive biomarker named NPI+IHC4 to predict pCR in ER+ breast cancer in a training set (n=443) and validated it in an external validation set (n=296). The results showed that a lower IHC4 score, NPI and NPI+IHC4 were significantly associated a high pCR rate in the entire cohort. In the study set, NPI+IHC4 showed a better sensitivity and specificity for pCR prediction (AUC 0.699, 95% CI 0.626-0.772) than IHC4 score (AUC 0.613, 95% CI 0.533-0.692), NPI (AUC 0.576, 95% CI 0.494-0.659), tumor size (AUC 0.556, 95% CI 0.481-0.631) and TNM stage (AUC 0.521, 95% CI 0.442-0.601). In the validation set, NPI+IHC4 had a better predictive value for pCR (AUC 0.665, 95% CI 0.579-0.751) than IHC4 score or NPI alone. In addition, ER+ patients with lower IHC4, NPI and NPI+IHC4 scores had significantly better DFS in both study and validation sets. In summary, NPI+IHC4 can predict pCR following NAC and prognosis in ER+ breast cancer, which is cost-effect and potentially more useful in guiding decision-making regarding NAC in clinical practice. Further validation is needed in prospective clinical trials with larger cohorts of patients.
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