Abstract P5-21-01: Effect of adjuvant systemic therapy in reducing rates of loco-regional recurrence in early-stage breast cancer: Results from nine NSABP randomized phase III trials

Abstract

Abstract Background Adjuvant systemic therapy reduces risk of distant recurrence (DR) and breast cancer death. In addition, adjuvant systemic therapy reduces risk of loco-regional recurrence (LRR). We examined the magnitude of the effect of adjuvant systemic therapy (tamoxifen, chemotherapy, and chemotherapy + trastuzumab) in reducing incidence rates and cumulative incidence rates of LRR as first event in nine recent NSABP randomized trials that were conducted from 1981 to 2005 and included a total of 21,815 patients. Methods Nine NSABP clinical trials of adjuvant (or neoadjuvant) systemic therapy, in which a reduction in LRR or DR was observed, were included in the analysis (NSABP B-13, B-14, B-19, B-20, B-21, B-27, B-28, B-30, and B-31). The cumulative incidence rates of LRR as the first disease-free survival (DFS) event were estimated and compared across treatment arms via log-rank tests. The sub-distribution proportional hazards models were applied to estimate the reduction in incidence rate of LRR from adjuvant systemic therapies. The corresponding magnitude of reduction in the incidence rate of any DFS event was estimated from Cox proportional hazards models. Results Across all nine clinical trials, adjuvant systemic therapy resulted in reductions in LRR that were comparable to or greater than the reductions in DFS events (Table). The observed reductions in LRR with adjuvant chemotherapy were of greater magnitude in trials of node-negative patients (35-58%) than in trials of node-positive patients (13-15%). Reductions in LRR were of similar magnitude with adjuvant chemotherapy as with adjuvant tamoxifen. In B-27, the sequential addition of neoadjuvant or adjuvant docetaxel to neoadjuvant AC reduced LRR rates by 27%. The addition of trastuzumab to adjuvant chemotherapy decreased LRR rates by 34%. Conclusions Rates of LRR have steadily declined over time in NSABP adjuvant clinical trials. This decline can be attributed to improvements in surgical and radiotherapy techniques but is also the result of the use of increasingly effective adjuvant systemic therapy. NSABP TrialPopulationTreatment ComparisonHR(95%CI)DFSHR(95%CI)LRR10-yr Cum Incidence of LRR(%)Log rank p-valueB-13 (n=1,084)N(-) / ER(-)MF v No Adj Rx0.66 (0.55,0.79)0.42 (0.29-0.62)5.9 v 13.5<0.001B-14 (n=4,028)N(-) / ER(+)TAM v Placebo0.70 (0.65, 0.77)0.54 (0.45-0.66)5.2 v 11.2<0.001B-19 (n=1,074)N(-) / ER(-)CMF v MF0.69 (0.57, 0.84)0.48 (0.31-0.73)5.3 v 10.0<0.001B-20 (n=2,299)N(-) / ER(+)CMF/MF+TAM v TAM0.76 (0.66, 0.88)0.57 (0.41-0.78)3.7 v 7.1<0.001B-21 (n=645)N(-) / ≤1cmTAM v Placebo0.93 (0.71, 1.21)0.65 (0.38-1.09)4.7 v 8.80.10B 27 (n=2,346)Operable T1-3 N0-1AC→T v AC (neoadj)0.92 (0.81, 1.05)0.73 (0.56-0.94)9.1 v 12.20.015B-28 (n=3,036)N(+)AC→P v AC0.90 (0.81, 1.00)0.87 (0.69-1.1)8.6 v 10.00.24B-30 (n=5,240)N(+) / HER2(-)AC→T v AT/TAC0.84 (0.76, 0.93)0.85 (0.65-1.1)4.6 v 5.40.23B-31 (n=2,063)N(+) / HER2(+)AC→P+H v AC→P0.59 (0.50, 0.69)0.66 (0.46-0.94)5 v 7.40.02N: Node; M: Methotrexate; F: 5-FU; TAM: Tamoxifen; C: Cyclophosphamide; A: doxorubicin; T: Docetaxel; P: Paclitaxel; H: trastuzumab Citation Format: Eleftherios P Mamounas, Gong Tang, Qing Liu, Jong-Heyon Jeong, Thomas B Julian, Priya Rastogi, Charles E Geyer, Sandra M Swain, Soonmyung Paik, D Lawrence Wickerham, Joseph P Costantino, Norman Wolmark. Effect of adjuvant systemic therapy in reducing rates of loco-regional recurrence in early-stage breast cancer: Results from nine NSABP randomized phase III trials [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-01.