Abstract PD3-02: Incidence of late relapse in HER2-positive (HER2+) breast cancer patients receiving adjuvant trastuzumab: Combined analysis of NCCTG (Alliance) N9831 and NSABP (NRG) B31
Authors: Chumsri S , Li Z , Serie DJ , Mashadi-Hossein A , Colon-Otero G , Song N , Pogue-Geile K , Gavin P , Paik S , Moreno-Aspitia A , Perez EA , Thompson EA 
Published: May 2019

Abstract
Background: Recent trials showed potential benefit of extended adjuvant endocrine therapy and relatively high risk of relapse after 5 years (yr) in hormone receptor-positive (HR+) HER2- breast cancer. While risk of late relapse in HR+ HER2- is fairly well defined, the risk of late relapse in HER2+ remains largely unknown. Method: 4547 HER2+ patients treated with adjuvant chemotherapy alone or combined with trastuzumab (TH) were included (3132 from North Central Cancer Treatment Group [NCCTG, now Alliance] N9831; 1415 from National Surgical Adjuvant Breast and Bowel Project [NSABP, now NRG] B-31). Intrinsic subtypes were assessed by Prosigna test. Kaplan-Meier method and Cox proportional hazards model were used for analysis. Results: Median follow-up was 10.4 yr in N9831 and 7.0 yr in NSABP-B31. 54.5% of pts had HR+ disease. Pts were classified as HER2 enriched (77.4%), Luminal B (10.1%), Luminal A (7.7%), and Basal (4.8%). In multivariate Cox regression analysis in both treatment groups, HR+ was significantly associated with improved recurrence-free survival (RFS) during the first 5 yr (HR 0.65, 95% CI 0.56-0.77, p&lt;0.001) but there was no significant difference during yr 5-10 (HR 1.32, 95% CI 0.93-1.88, p=0.12). In HR+HER2+ pts treated with TH, cumulative hazard for relapse or death was lower in the first 5 yr (10.96%, 95%CI 8.78-13.08) compared to HR-HER2+ (17.48%, 95%CI 14.59-20.27), with adjusted HR 0.60 (95%CI: 0.45-0.79, p&lt;0.001). Unlike HR+HER2- disease, cumulative hazard of relapse or death in yr 5-10 in HR+HER2+ pts treated with TH was lower at 8.6% (95%CI 6.16-10.97). This is slightly higher than pts with HR-HER2+ at 5.75% (95%CI 3.18-8.24, adjusted HR=1.7, 95%CI 1.01-2.85, p=0.046). Compared to 22% and 31% risk of relapse after 5 yr in N0 and N1 HR+HER2- in recent publication, 3.23% (95%CI 0-9.25) of pts with HR+HER2+ with N0 developed recurrence in yr 5-10 and 6.39% (95%CI 3.09-9.59) in those with N1 disease. Albeit rare, pts with Luminal A tumors had 89.8% relapse-free survival at 10 yr compared to Luminal B 82.3%, HER2 enriched 76.8%, and Basal 74.19%. Conclusions: Even without extended adjuvant endocrine therapy in both trials, risk of late relapse in HR+ HER2+ appeared to be low, particularly in pts with N0 or N1 disease. The benefit of extended adjuvant endocrine therapy in this group of TH pts, particularly those with no lymph node involvement, may not outweigh side effects of continuing endocrine therapy beyond 5 yr.
Support: U10CA180821, U10CA18082, U24CA196171; U10CA180868, UG1CA189867, U10CA180822, U24CA196067; ClinicalTrials.gov Id: NCT00005970, NCT00004067
Cumulative probability (%) of relapse or death.Nodal statusYear 0-5Year 5-10* HR+HR-HR+HR- Cumulative hazard (95%CI)Cumulative hazard (95%CI)Cumulative hazard (95%CI)Cumulative hazard (95%CI)07.71 ( 0.00, 15.74)16.05 ( 7.98, 23.42)3.23 ( 0.00, 9.25)8.86 ( 1.05, 16.04)16.70 ( 3.66, 9.64)10.63 ( 5.99, 15.04)6.39 ( 3.09, 9.59)5.57 ( 1.46, 9.51)213.68 ( 7.42, 19.52)20.99 (12.98, 28.26)5.10 ( 0.64, 9.35)1.22 ( 0.00, 3.57)310.25 ( 2.76, 17.17)39.76 (24.11, 52.18)13.19 ( 3.54, 21.88)8.52 ( 0.00, 19.16)*Based on pts who survived 5 yr without relapse
Citation Format: Chumsri S, Li Z, Serie DJ, Mashadi-Hossein A, Colon-Otero G, Song N, Pogue-Geile K, Gavin P, Paik S, Moreno-Aspitia A, Perez EA, Thompson EA. Incidence of late relapse in HER2-positive (HER2+) breast cancer patients receiving adjuvant trastuzumab: Combined analysis of NCCTG (Alliance) N9831 and NSABP (NRG) B31 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-02.