Abstract S6-02: Long-term prognostic value of residual cancer burden (RCB) classification following neoadjuvant chemotherapy
Authors: Symmans WF , Wei C , Gould R , Zhang Y , Hunt KK , Buchholz TA , Valero V , Hortobagyi GN , Pusztai L , Hatzis C 
Published: August 2014

Abstract
Background: In 2007 we described residual cancer burden (RCB) as a measure of pathologic response after neoadjuvant chemotherapy and demonstrated that RCB was strongly prognostic for 5-year survival outcomes. Herein, we update the long-term outcome of this original cohort, validate our results in an independent patient group, and report outcome according to hormone receptor (HR) and HER2 receptor status.
Methods: Our original RCB development cohort received paclitaxel followed by fluorouracil, doxorubicin and cyclophosphamide (T/FAC) and the original validation cohort received FAC alone as neoadjuvant chemotherapy for stage II or III breast cancer (JCO 2007;25:4414-22). We subsequently evaluated RCB in 2008 in another independent validation cohort of patients treated with neoadjuvant T/FAC. These patient cohorts were followed up until 2013. The T/FAC cohorts were combined to test RCB within phenotypic subsets of HER2+, HR+/HER2-, and triple receptor-negative breast cancer (TNBC). Pre-defined RCB classes of pathologic complete response (pCR), minimal (RCB-I), moderate (RCB-II) and extensive (RCB-III) residual disease were compared with respect to relapse-free survival (RFS) using the likelihood ratio test and estimates of 10-year RFS (with 95% confidence interval) were determined from Kaplan-Meier analysis. We excluded patients with HER2-positive (HER2+) cancer who received neoadjuvant or adjuvant trastuzumab.
Results: Median follow up of event-free survivors was 142 months for the original T/FAC development cohort (N = 220), 91 months for the T/FAC validation cohort (N = 277), and 198 months for the FAC (N = 169) cohort. The estimates of 10-year RFS by RCB class for each cohort, respectively, were 86%, 81% and 95% for pCR; 87%, 81% and 85% for RCB-I; 76%, 62%, and 62% for RCB-II; and 38%, 36% and 38% for RCB-III. Table 1 presents the frequency and the estimates of 10-year RFS for each RCB class within each phenotypic subset of breast cancer (HER2+, TNBC, and HR+/HER2-) in the combined T/FAC cohorts (N = 497).
Frequency and estimated 10-year RFS of RCB classes in breast cancer subsets after T/FAC chemotherapy HER2+TNBCHR+/HER2-RCB ClassFreqRFS (95% CI)FreqRFS (95% CI)FreqRFS (95% CI)pCR36%83% (66 to 92)35%82% (63 to 92)10%83% (59 to 93)RCB-I16%69% (41 to 86)15%82% (53 to 94)13%96% (74 to 99)RCB-II30%50% (31 to 66)33%54% (38 to 68)60%76% (68 to 83)RCB-III18%32% (13 to 52)17%18% (6 to 36)17%45% (27 to 61)RFS, relapse-free survival; Freq, frequency; CI, confidence interval.
RCB was prognostic in all cohorts and subgroups (p&lt;0.001). The hazard rate (per year) associated with RCB-III and RCB-II was highest during the first 3 years for HER2+ and TNBC but was similar to pCR/RCB-I beyond 6 years. However, for HR+/HER2- cancers the annual hazard rate was consistent during the first decade, at 6%-8% for RCB-III and 2% for RCB-II.
Conclusions: RCB after neoadjuvant chemotherapy was strongly prognostic in all phenotypic subsets of breast cancer patients over a decade of follow up, even for HR+/HER2- cancers. In HER2-negative breast cancers, RCB-I had similar prognosis to pCR, whereas RCB-III for HR+/HER2- and RCB-II/III for TNBC defined high-risk patient populations following neoadjuvant chemotherapy.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-02.