Abstract S6-02: Long-term prognostic value of residual cancer burden (RCB) classification following neoadjuvant chemotherapy

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<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.

Relationship between Complete Pathologic Response to Neoadjuvant Chemotherapy and Survival in Triple-Negative Breast Cancer

“…We assumed that the pCR rate for the control arm (TNBC treated with thirdgeneration chemotherapy) is 30% and that the 10-year RFS of patients who achieved pCR is 82% for both arms corresponding to an exponential hazard rate l pCR of 0.0198 (events/year; ref. 19). Under these assumptions, the survival function of the entire cohort for each arm will be the mixture of the survival functions of the pCR and RD groups.…”

“…We used survival data from 127 clinical stage I-III TNBC cases from our previously published cohort from MD Anderson Cancer Center (6) with recently updated survival outcomes (19). TNBC status was defined as ER and PR <1% positivity by routine IHC and lack of HER2 amplification by FISH (HER2:CEP17 copy number ratio <2.0) or HER2 IHC score of 0.…”

Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial

“…Its principal shortcoming is the lack of comparison with the baseline core biopsy but from a clinical point of view the tumour burden following chemotherapy is a sensible feature to measure and has been shown to correlate well with outcomes at 10 years follow up. 15 One of the important aspects of ARTemis is the future programme of translational research and that has required sections from core biopsies, excised tumours and nodes to be marked up for future tissue sampling. A pathologist would certainly be required to support that aspect of a future trial.…”

Zoledronate for patients with invasive residual disease after anthracyclines-taxane-based chemotherapy for early breast cancer – The Phase III NeoAdjuvant Trial Add-oN (NaTaN) study (GBG 36/ABCSG 29)

“…Taking this recent evidence into account, several lessons from this negative study can be taken as guidance for the next generation of trials in this setting: Patients should be selected by tumour subtype as the risk of relapse varies significantly; only non-pCR patients with triple-negative or HER2-positive disease show sufficiently high relapse rates, allowing their unselected accrual in such trials. For patients with HRpositive/HER2-negative residuals further selection of high-risk patients is necessary; potential selection criteria are a high clinicopathological score-estrogen receptor and grade (CPS-EG) score [16], or high residual cancer burden [17].…”