Outcome of Patients With an Ultralow-Risk 70-Gene Signature in the MINDACT Trial. Issue 12 (20th April 2022)

• Record Type: Journal Article
• Authors: Lopes Cardozo, Josephine M.N.; Drukker, Caroline A.; Rutgers, Emiel J.T.; Schmidt, Marjanka K.; Glas, Annuska M.; Witteveen, Anke; Cardoso, Fatima; Piccart, Martine; Esserman, Laura J.; Poncet, Coralie; van 't Veer, Laura J.
• Is Part Of: Journal of clinical oncology. Volume 40:Issue 12(2022)
• Page Start: 1335
• Page End: 1345
• Publication Date: 2022-04-20
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.21.02019
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: Patients with 70-gene signature ultralow-risk breast cancers have shown excellent survival in historic cohorts, including randomized trials. The ultralow-risk subgroup was characterized to help avoid overtreatment. We evaluated outcomes of ultralow-risk patients in the largest cohort to date. METHODS: Of the 6, 693 patients enrolled in the EORTC-10041/BIG-3-04 randomized phase III MINDACT trial, profiling revealed an ultralow-risk 70-gene signature in 1, 000 patients (15%). Distant metastasis-free interval (DMFI) and breast cancer–specific survival (BCSS) were assessed in patients stratified by 70-gene signature result (high, low, and ultralow) by Kaplan-Meier analysis and hazard ratios with 95% CI from Cox regression. RESULTS: Median follow-up was 8.7 years. Of the ultralow-risk patients (n = 1, 000), 67% were > 50 years, 81% had tumors ≤ 2 cm, 80% were lymph node–negative, 96% had grade 1 or 2 tumors, and 99% were estrogen receptor (ER)-positive. Systemic therapy was received by 84% of patients (69% endocrine therapy, 14% endocrine therapy plus chemotherapy, 1% other) and 16% received no adjuvant systemic treatment. The 8-year DMFI for ultralow-risk patients was 97.0% (95% CI, 95.8 to 98.1), which was 2.5% higher than for patients with low-risk tumors (n = 3, 295, 94.5% [95% CI, 93.6 to 95.3]). The hazard ratio for DMFI was 0.65 (95% CI, 0.45 to 0.94) for ultralow versus low risk, after adjusting for clinical-pathologic and treatment characteristics. The 8-year BCSS for ultralow-risk patients was 99.6% (95% CI, 99.1 to 100). CONCLUSION: Patients with an ultralow-risk 70-gene signature have the best prognosis, distinctive from low risk, with 8-year BCSS above 99%, and very few patients developed distant metastases with an 8-year DMFI rate of 97%. These patients could be candidates for further de-escalation of treatment, to avoid overtreatment and the risk of side effects.