Abstract P2-03-01: Are all small tumors low risk? Characterization of small invasive node negative breast cancers (BC) enrolled in the EORTC 10041/BIG 3-04 (MINDACT) trial

Background: Adjuvant systemic therapy for subcentimetric N0 BC is controversial. These tumors have good prognosis, but a subgroup has high risk of relapse and requires adjuvant therapy. The best tool to identify this subgroup is unknown. We clinically and biologically characterize pT1abN0M0 tumors from patients enrolled in MINDACT.Patients and Methods: All MINDACT pts with pT1abN0 tumors were included. Descriptive statistical analysis included age, menopausal status, centrally assessed tumor grade, Ki67, ER, PR and HER-2 status. Cut-off value for high Ki67 was 20%. IHC subtypes are per 2013 St. Gallen consensus/ ESMO guidelines. Genomic tests (Mammaprint, Targetprint, BluePrint) were performed and their concordance rate with central pathology evaluated. We report clinical (modified version of adjuvant online!) and genomic risk assessment (MammaPrint) for these patients. Survival data will be reported after MINDACT primary analysis.Results:826 patients with T1abN0 tumors were enrolled in MINDACT, [12.3% of all patients (6694) and 16% of all N0 tumors];310 (35%) patients were ≥ 60 years and 537 (65%) were postmenopausal. Most (710;86%) samples were tested by central pathology. Tumors were mainly ductal (579;81.5%), ER + (650;91.5%), and PR+ (593;83.5%);44(6.2%)were HER-2 +; 520 (73.2%) had a low Ki67&174 (24.5%) had high Ki-67 labeling index; 80 (11.3%) were grade 3 & 328 (46.2%) grade 2 tumors. According to Targetprint, 761/826 (92.1%) tumors were ER+; 624/826 (75.5%) PR+; 45/826 (5.4%) HER2+. Concordance between Targetprint and central pathology was higher for ER (kappa= 0.90) and lower for PR and HER2 (kappa=0.60 and 0.73 resp).Molecular subtype classification by IHC surrogates showed 420/710 (59.2%) Luminal A tumors; 189/710 (26.6%) Luminal B; 36/710 (5.1%) Luminal B/ HER2+; 8/710 tumors (1.1%) HER-2 + and 37/710 (5.2%) TNBC. Using BluePrint 739/826 (89.5%) were Luminal; 29/826 (3.5%) HER-2 + and 58/826 (7.0%) basal. Combining BluePrint and MammaPrint 609/826 (73.7%) tumors were Luminal A&129/826 (15.6%) Luminal B. Agreement between Mammaprint and Ki67 for distinction of luminal A vs B/HER-2 neg. tumors was low (kappa=0.31), similar to the overall MINDACT results (kappa=0.35).Using clinical risk assessment 820/826 (99.3%) were low-risk (CL). Using genomic risk assessment 624/826 (75.5%) were low risk (GL) and 201/826 (24.3%) were high-risk (GH). Overall, 624/826 (75.5%) were both CL/GL and 196/826 (23.7%) were CL/GH. The percentage of discordant CL/GH cases among T1abN0 tumors (196/826, 23.7%) is higher than in all MINDACT cohort (592/6694, 8.9%) and among T1c-2-3N0 tumors (381/4462, 8.5%). T1ab tumors were mainly 720/826 (87.2%) treated with BCS and radiotherapy; adjuvant treatment and compliance rate will be available at the meeting. Conclusions:1) Results show biological characteristics are relevant for T1abN0 BC& that size/nodal status could be insufficient determinants of adjuvant systemic therapy. 2) A significant portion (23.7%) of such tumors, clinically classified as low risk, was genomically high risk by MammaPrint.3) IHC surrogates don9t always accurately reflect genomic molecular subtyping. Citation Format: Giuseppe Viale, Femke Snoo, Laura Van9t Veer, Emiel Rutgers, Martine Piccart, Jan Bogaerts, Fatima Cardoso, Konstantinos Tryfonidis, Leen Slaets. Are all small tumors low risk? Characterization of small invasive node negative breast cancers (BC) enrolled in the EORTC 10041/BIG 3-04 (MINDACT) trial [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 P2-03-01.