As reported in the Journal of Clinical Oncology by Josephine M.N. Lopes Cardozo, MD, and colleagues, long-term follow-up in the phase III MINDACT trial has shown excellent outcomes among a large group of patients with ultra-low–risk breast cancer as classified by the 70-gene signature assay, with outcomes in this group clearly distinguishing between ultra-low risk and low risk.
In the European MINDACT trial, 6,693 patients with early breast cancer enrolled between 2007 and 2011 were divided into three groups: those with low genomic risk and low clinical risk (using Adjuvant! Online) received no systemic adjuvant chemotherapy; those with high genomic and clinical risk received adjuvant chemotherapy; and those with discordant results were randomly assigned to receive adjuvant chemotherapy or no chemotherapy based on clinical or genomic risk.
Study Details
For the 70-gene signature assay, a score of ≤ 0 is classified as high risk and a score > 0 is classified as low risk. For the current study, a score of > 0.355 was classified as ultra-low risk. Among the 6,693 patients, 1,000 (15%) had ultra-low risk.
Distant metastasis–free interval, defined as the time until first distant metastasis or breast cancer–related death (including death from unknown cause), was the primary outcome measure.
Patients with an ultra-low–risk 70-gene signature have the best prognosis, distinctive from low-risk, with 8-year breast cancer–specific survival above 99%, and very few patients developed distant metastases, with an 8-year distant metastasis¬–free interval rate of 97%. These patients could be candidates for further de-escalation of treatment, to avoid overtreatment and the risk of side effects.— Josephine M.N. Lopes Cardozo, MD, and colleagues
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Key Findings
Among the patients with ultra-low–risk scores, 67% were aged > 50 years, 81% had tumors ≤ 2 cm, 80% were lymph node–negative, 96% had grade 1 or 2 tumors, and 99% were estrogen receptor–positive. Adjuvant systemic therapy was received by 84%, including endocrine therapy in 69% and endocrine therapy plus chemotherapy in 14%; 16% received no adjuvant systemic treatment.
Median follow-up was 8.7 years. The 8-year distant metastasis–free interval differed significantly across risk groups (overall P < .0001). Rates were 97.0% (95% confidence interval [CI] = 95.8%–98.1%) among ultra-low–risk patients vs 94.5% (95% CI = 93.6%–95.3%) among 3,295 low-risk patients. In analysis adjusting for clinical-pathologic and treatment characteristics, the hazard ratio (HR) for ultra-low vs low risk was 0.65 (95% CI = 0.45–0.94). Among 2,398 patients with high-risk tumors, the 8-year distant metastasis–free interval was 89.2% (95% CI = 87.9%–90.5%; HR vs low risk = 2.17, 95% CI =1.68–2.80).
The 8-year breast cancer–specific survival differed significantly across risk groups (overall P < .0001). Rates were 99.6% (95% CI = 99.1%–100%) among ultra-low–risk patients, 98.2% (95% CI = 97.7%–98.7%) among low-risk patients, and 93.7% (95% CI = 92.6%–94.7%) among high-risk patients.
The investigators concluded, “Patients with an ultra-low–risk 70-gene signature have the best prognosis, distinctive from low-risk, with 8-year breast cancer–specific survival above 99%, and very few patients developed distant metastases, with an 8-year distant metastasis–free interval rate of 97%. These patients could be candidates for further de-escalation of treatment, to avoid overtreatment and the risk of side effects.”
Laura J. van’t Veer, PhD, of the Department of Laboratory Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the EORTC Breast Cancer Group, Netherlands Cancer Institute, and others. The MINDACT study was supported by the Breast Cancer Research Foundation, Novartis, F. Hoffmann-La Roche, Sanofi-Aventis, Eli Lilly, Veridex, Susan G. Komen for the Cure, and others. For full disclosures of the study authors, visit ascopubs.org.
