ORIGINAL ARTICLE – BREAST ONCOLOGY Tumor Response Ratio Predicts Overall Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy Marian Miller, MD 1 , Rebecca A. Ottesen, MS 2 , Joyce C. Niland, PhD 2 , Laura Kruper, MD, MSCE 1 , Steven L. Chen, MD, MBA 1 , and Courtney Vito, MD 1 1 Department of Surgical Oncology, City of Hope, Duarte, CA; 2 Department of Information Sciences, City of Hope, Duarte, CA ABSTRACT Background. Neoadjuvant chemotherapy (NAC) is com- monly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I–III breast cancer who had NAC and pretreatment imaging at City of Hope (1997–2010). Patient demographics, tumor characteristics, and OS were ana- lyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR [ 0–0.4 (strong partial response, SPR), TRR [ 0.4–1.0 (weak partial response, WPR), or TRR [ 1.0 (tumor growth, TG). OS was esti- mated by the Kaplan–Meier method and tested by the log- rank test. Cox regression was performed to evaluate asso- ciations between OS and TRR in a multivariable analysis while controlling for potential confounders. Results. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that signifi- cantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be sta- tistically significant by multivariable analysis (p = 0.016). Conclusions. TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC. Although initially only used in patients with inflamma- tory or inoperable breast cancer, neoadjuvant chemotherapy (NAC) has seen expanded use in patients across almost all stages of breast cancer. 1 The goal of NAC is to shrink the primary tumor and minimize the extent of necessary surgical resection. The use of NAC also serves as an in vivo assay for treatment efficacy. 1 As a result, treatment strategies for patients with stage II and III breast cancer have evolved and continue to adapt. However, staging approaches—and consequently prognostication— have not advanced at the same pace. Currently, pathologic staging of breast cancer is per- formed using the American Joint Committee on Cancer (AJCC) tumor, node, metastasis classification system, which is universally applied to both determine prognosis and to guide therapy. 2 This system is based on the size of the tumor (T) and the number of positive lymph nodes (N) obtained during surgery, as well as the existence of metastases (M). A pathologic complete response (pCR) to neoadjuvant therapy seen at the time of surgery has been shown to predict improved overall survival (OS). 3 How- ever, the prognosis for patients with partial response remains unclear. Furthermore, other than the ‘‘y’’ notation, which categorizes the extent of tumor actually present at the time of surgery, AJCC staging does not specifically take into account the effects of NAC on the tumor. 2 This raises questions as to how best to stage the breast cancer of patients in the neoadjuvant setting. Several methods have been proposed to modify the current staging system. Symmans et al. proposed Ó Society of Surgical Oncology 2014 First Received: 14 April 2014; Published Online: 25 July 2014 C. Vito, MD e-mail: cvito@coh.org Ann Surg Oncol (2014) 21:3317–3323 DOI 10.1245/s10434-014-3922-0