115P Longterm prognostic utility of 70-gene signature by clinical and genomic risks, including Ultralow (gUL) risk patients (pts)

Abstract

In the MINDACT trial, 4 risk categories (RC) by clinical (c) and genomic (g) risks were defined. In cHigh/gLow risk patients (pts) with no adjuvant chemotherapy (CT), 8y-Distant Metastases Free Survival (DMFS) was 89.4 % [95% CI 86.2-91.5]. MP also identified a third subgroup of gUL pts (score 0.355 – 1.0, 15% in MINDACT), with an excellent prognosis and no benefit from extended endocrine therapy (EET). We aimed to study: DFS/ DMFS by the 6 RC resulting from combining the 2 (c) categories with the 3 (g) groups; the timing of recurrences; and the putative benefit of EET for each genomic group. All ER+/HER2- BC pts with MP data diagnosed between 2012-2017 at Vall d'Hebron University Hospital were selected. cLow risk was defined as in MINDACT trial. To study the benefit of EET, a landmark analysis at 5y from ET initiation was conducted. 140 pts were identified. Baseline features: 47.8% premenopausal; stage I/II: 74%/26%; histological grade 1/2/3: 19.6%/74.9%/6.5%. cLow/cHigh: 67%/33%; gUL/gLow-Non-Ultralow (LNUL)/gHigh: 11.4%/53.6%/35%. PgR and Ki67 tended to correlate with MP g risks, but only the IHC-subtype reached statistically significance. Systemic adjuvant treatments [N/%]: ET 138/98.5%; ovarian function suppression for premenopausal pts 23/35%; CT: 45/32%; EET: 49/35.8%. After 8y-median FU, 15 DFS events and 11 DMFS were observed. DMFS in cHigh/gLow (UL+LNUL) without CT was 90.6% [81.1%; 100%]. DFS/DMFS rates by each c/g category are depicted in the table. Only 4 DMFS events occurred after 5 years, precluding to explore EET role by RCTable: 115PcLow-gULcLow-gLNULcLow-gHighcHigh-gULcHigh-gLNULcHigh-gHighN (%)13 (9.4)45 (32)35 (25)3 (2.2)30 (22)13 (9.4)8y-DFS (%)1009184.81009076.9CI 95%-83.2-99.871.6-100-79.9-10057.1-1008y-DMFS (%)10095.589.11009084.6CI 95%-89.6-10077.7-100-79.9-10067.1-1008y-DMFS (%)cHigh-gLow (UL+LNUL) No CT90.6% (CI 95% 81.1-100)8y-DMFS (%) in Mindact TrialcHigh-gLow (UL+LNUL) No CT89.4% (CI 95% 86.2-91.5) Open table in a new tab . In our series, DMFS rate in cHigh-gLow pts without CT was similar to that reported in MINDACT trial. In line with prior reports, gUL pts had excellent survival, while cHigh-gHigh group showed significantly poorer outcome. Albeit limited by small sample size, classification in 6 RCs instead of 4 seems useful to redefine prognosis. Additional FU is warranted to determine the EET benefit in each RC.