109O Adjuvant endocrine therapy for premenopausal invasive lobular carcinoma (ILC): Results from SOFT and TEXT phase III studies

Data from BIG1-98 along with pre-clinical findings point to a partial resistance to tamoxifen (T) among postmenopausal women diagnosed with ILC. The TEXT and SOFT trials assigned premenopausal women with hormone receptor-positive (ER+) tumors to exemestane plus ovarian function suppression (E+OFS) or T + OFS, or to T alone in SOFT only. This analysis includes centrally reviewed ER+HER2-negative tumors (n=4115) classified as invasive ductal carcinoma (IDC), (n=3370) or ILC (n=345). Cox model analyses stratified by trial and chemotherapy use included histological subtype, treatment, and interaction term. A pre-specified level of significance P-interaction<0.2 was selected to retain statistical power (>80%). The analyses were adjusted by age, tumor size, nodal status, and centrally assessed Ki67 to define Luminal A-like (LA), (Ki67 < 14%) and LB-like tumors (Ki67 ≥ 14%). The primary endpoint was breast cancer free interval (BCFI). At 12-yr of median follow-up in the SOFT trial, E+OFS showed a larger treatment benefit over T in ILC (HR=0.32; 95%CI 0.12-0.91) than in IDC (HR=0.71; 95%CI 0.54-0.93), Pinteraction=0.15. Differences were less marked for T+OFS vs. T, ILC (HR=0.66 95%CI 0.31-1.42) and IDC HR=0.81 95%CI 0.63-1.05), Pinteraction=0.62. In SOFT+TEXT at 13-yrs, E+OFS vs. T+OFS consistently benefited ILC (HR=0.60 95%CI 0.31-1.15) and IDC (HR=0.70 [95%CI 0.58-0.85), Pinteraction=0.65. The table below shows consistent benefit E+OFS vs T or T+OFS for both LA and LB-like ILC tumors. In contrast LB-like IDC benefitted more from E+OFS vs. T+OFS, with LA-like IDC showing a much smaller benefit.Table: 109OTxN ptsTx HR (95% CI)Tx HR (95% CI)IDCILCIDCILCSOFTLA-likeE+OFS190310.60 (0.35-1.04)0.16 (0.03-0.78)T18320LB-likeE+OFS380240.74 (0.54-1.03)0.58 (0.14-2.33)T40722SOFT+TEXTLA-likeE+OFS341650.93 (0.59,1.47)0.48 (0.15,1.56)T+OFS35073LB-likeE+OFS952790.64 (0.52,0.79)0.70 (0.31,1.58)T+OFS97967 Open table in a new tab The benefits favoring OFS+E appeared to be greater for ILC when compared to IDC, overall and consistent within subgroups of LA- and LB-like tumors defined by Ki-67. E+OFS stands out as the most effective treatment for ILC.