Not all small node negative (pT1abN0) breast cancers are similar: Outcome results from an EORTC 10041/BIG 3-04 (MINDACT) trial substudy

Abstract

Background: Adjuvant systemic therapy for pT1abN0 breast cancer is controversial, as these tumors overall have a low relapse risk. The best tool to identify a subgroup that would benefit from adjuvant treatment is unknown. Methods: This subgroup included patients with pT1abN0 tumors enrolled in MINDACT who had both their genomic risk G (per MammaPrint®) & clinical risk C (per a modified version Adjuvant! Online) assessed. Patients characterized as low‐risk in both assessments were spared chemotherapy (CT), while in those characterized as C&G high CT was advised. Discordant cases were randomized to receive CT based on the C or the G result. Here, we report the 5‐year rates of distant metastasis‐free survival (DMFS), distant metastases‐free interval (DMFI) & overall survival (OS) for pT1abN0 patients who received or not CT based on their G or C risk result. Results: 826/6693 (12.3%) patients with pT1abN0 tumors were enrolled in MINDACT. 310/826 (37.5%) were ≥ 60 years & 525/826 (63.6%) postmenopausal. 727/826 samples were reviewed by central pathology; 585/727 (80.5%) were invasive ductal, 662/727 (91.1%) ER positive, 46/727 HER2 positive (6.3%) & 81/727 (11.1%) were grade 3 tumors. IHC subtype classification identified 426/727 (58.6%) as Luminal A; 193/727 (26.5%) Luminal B; 38/727 (5.2%) Luminal B/HER2 positive; 8/727 (1.1%) HER2‐ positive; 37/727 (5.1%) triple‐negative tumors. Almost all patients (820/826; 99.3%) were clinical low‐risk (CL). Overall, 624/826 (75.5%) were CL/GL & 196/826 (23.7%) were CL/GH (5 patients were CH/GL, no cases were CH/GH, 1 missing). 5‐year DMFS for patients with CL/GH pT1abN0 tumors who received CT was 97.3% (95% CI, 89.4‐99.3) vs 91.4% (95% CI, 82.6‐95.9) for those who did not. 5‐years DMFI & OS for these patients treated with CT were 98.8% (95% CI, 91.9‐99.8) & 98.5% (95% CI, 89.6‐ 99.8) vs 91.4% (95% CI, 82.6‐ 95.9) & 95.8% (89.1‐ 98.4%) respectively for those who did not receive CT. Conclusions: Biological characteristics can be used as determinants of adjuvant CT administration for T1abN0 tumors. An important portion (23.7%) of these small tumors was CL but GH (MammaPrint®) risk and derived a benefit from CT. Clinical trial identification: The main MINDACT study: ClinicalTrials.gov number: NCT00433589, EudraCT number:2005‐002625‐31 Legal entity responsible for the study: European Organization for Research and Treatment of Cancer (EORTC) Funding: None Disclosure: L. Van 't Veer: Personal fees and other support from Agendia NV outside the submitted work. Co‐ inventor on a patent related to MammaPrint: Diagnosis and prognosis of breast cancer patients (WO2002103320, licensed to Agendia, NV). M. Piccart: Consulting or advisory role for AstraZeneca, MSD, Novartis, Pfizer, Roche‐ Genentech, Periphagen, Huya, Debiopharm, PharmaMar, Radius. Research funding from most above mentioned companies. F. Cardoso: Consultancy/research grants from Astellas/Medivation, AstraZeneca, Celgene, Daiichi‐ Sankyo, Eisai, GE Oncology, Genentech, Glaxo Smith Kline (GSK), Macrogenics, Merck‐ Sharp, Merus BV, Novartis, Pfizer, Pierre‐ Fabre, Roche, Sanofi and Teva. All other authors have declared no conflicts of interest.