Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

• DOI: 10.1200/jco.2015.63.1010
• Publication Date: 2017-02-23T17:11:27Z
• Authors: W. Fraser Symmans; Caimiao Wei; Rebekah Gould; Xian Yu; Ya Zhang; Mei Liu; Andrew Walls; Alex Bousamra; Maheshwari Ramineni; Bruno Sinn; Kelly Hunt; Thomas A. Buchholz; Vicente Valero; Aman U. Buzdar; Wei Yang; Abenaa M. Brewster; Stacy Moulder; Lajos Pusztai; Christos Hatzis; Gabriel N. Hortob...
• Keywords: Neoplasm, Residual; Paclitaxel; Receptor, ErbB-2; Breast Neoplasms; Middle Aged; Prognosis; Disease-Free Survival; Neoadjuvant Therapy; 3. Good health; Phenotype; Receptors, Estrogen; Chemotherapy, Adjuvant; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Humans; Female; Fluorouracil; Prospective Studies; Receptors, Progesterone; Cyclophosphamide; Epirubicin

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.