The American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines on the use of biomarkers to guide adjuvant therapy for early-stage invasive breast cancer provide new recommendations in a focused update following the publication of the “Microarray in node-negative and one to three positive lymph node disease may avoid chemotherapy” (MINDACT) study.
The MINDACT study, an international, prospective randomized trial assessed the clinical utility of the 70-gene signature in addition to the standard clinico-pathological criteria in selecting early breast cancer patients for adjuvant chemotherapy. It was managed and sponsored by the European Organisation of Research and Treatment of Cancer (EORTC) as part of an extensive an complex partnership in collaboration with the BIG, Agendia, and a great many other academic and commercial partners, as well as patient advocates. This study included 6,693 women with histologically proven operable invasive breast cancer, zero to three positive nodes, and no distant metastases, recruited from 2007 to 2011 in 112 centers in nine European countries.
Based on the results of the MINDACT study, ASCO recommended that the MammaPrint assay could be used to guide decisions on withholding adjuvant systemic chemotherapy in patients at high clinical risk of recurrence per MINDACT categorization and:
- with ER/PgR-positive , HER2-negative, lymph node–negative breast cancer
- with ER/PgR-positive , HER2-negative and one to three positive lymph nodes breast cancer
ASCO therefore did not recommend the use of the MammaPrint assay in patients determined to be at low clinical risk of recurrence per MINDACT categorization.
Reduction of overtreatment in patients with early-stage breast cancer is an important goal which has a societal as well as individual impact in patients with ER/PgR–positive disease.
An overview of the trial’s results is given below:
Each participant’s genomic risk was determined by using the MammaPrint assay and clinical risk by using a modified version of Adjuvant! Online (version 8.0 with HER2 status). Individuals with both low clinical and low genomic risk did not receive chemotherapy, and those at high clinical and high genomic risk received adjuvant chemotherapy. Those with discordant clinical and genomic risk (high/low or low/high) were randomly assigned to receive chemotherapy or not.
The primary analysis of this EORTC study was to assess whether, among patients with high clinical and low genomic risk not receiving chemotherapy, the lower boundary of the 95% CI for the rate of 5-year distant metastasis–free survival (DMFS) was 92% or greater.
Of all participants, 5,914 (88.4%) had ER/PgR–positive, 6,043 (90.3%) had HER2-negative, and 640 (9.6%) had triple-negative tumors. Overall, 2,745 (41.0%) patients had tumors with low clinical and low genomic risk, 592 (8.8%) with low clinical and high genomic risk, 1,550 (23.2%) with high clinical and low genomic risk, and 1,806 (27.0%) with high clinical and high genomic risk. At the time of the cutoff date for analysis, the median follow-up time was 5 years. Of the 644 women included in the primary test population (those with high clinical and low genomic risk who did not receive chemotherapy), the DMFS at 5 years was 94.7% (95% CI, 92.5%to 96.2%), demonstrating a lower boundary of the 95% CI for the 5-year DMFS of at least 92% (primary objective met). In the corresponding subgroup of patients with ER/PgR-positive, HER2-negative and lymph node negative breast cancer (with high clinical but low genomic risk), the 5-year DMFS rate was 93.9% (95% CI, 90.6% to 96.1%) in those assigned to endocrine therapy only and 95.5% (95% CI, 92.5% to 97.3%) in those assigned to receive chemotherapy.