A large subset analysis of the MINDACT trial suggests that oncologists may be undertreating women with small (< 1 cm) node-negative breast tumors, which are clinically considered to be low risk but can be genomically high risk. About one in four women with small node-negative breast tumors < 1 cm turned out to have tumors with high genomic risk that are biologically aggressive and may benefit from chemotherapy.1 Results were presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid.
Treatment decisions must take into account the biology of the disease.— Konstantinos Tryfonidis, MD
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“Patients with node-negative tumors < 1 cm have been traditionally excluded from adjuvant chemotherapy trials due to their favorable prognosis. In this exploratory analysis, it was shown that these smaller tumors are mainly hormone receptor–positive, and based on the 70-gene (MammaPrint) signature, 24% were considered to be genomically high-risk. Patients with genomic high/clinical low risks on MammaPrint and a modified version of Adjuvant! Online seem to derive a benefit in terms of distant metastasis–free survival and disease-free survival from adjuvant chemotherapy admininstration. These results indicate that treatment decisions must take into account the biology of the disease and not just tumor burden,” stated lead author Konstantinos Tryfonidis, MD, of the European Organisation for Research and Treatment of Cancer (EORTC), Brussels.
MINDACT was the first prospective study to assess the utility of the 70-gene MammaPrint genetic signature in patients with breast cancer. The main analysis of MINDACT in 6,693 patients showed that patients with primary invasive early breast cancer at clinically high-risk/genomically-low risk of recurrence did not experience a significant benefit in distant metastasis–free survival from adjuvant chemotherapy.2
Fatima Cardoso, MD
“The genomic high-risk/clinical low-risk and genomic low-risk/clinical high-risk patients are considered with discordant risk assessment, and they were randomized to use either the genomic or the clinical risk for adjuvant chemotherapy administration,” Dr. -Tryfonidis reminded listeners. “In the overall trial, 46% of patients with a high clinical risk score were able to safely forgo chemotherapy.”
Co–principal author of MINDACT, Fatima Cardoso, MD, Director of the Breast Unit, Champalimaud Clinical Centre, Lisbon, commented on the latest analysis of the trial. “Traditionally, node-negative small breast cancers have been considered low-risk, for which adjuvant chemotherapy is unnecessary. However, recent advances in cancer biology have shown that while tumor burden is still independently prognostic, tumor biology is key for outcome. In this subset analysis of MINDACT, we have clearly shown that one in four small node-negative tumors are biologically aggressive and [patients with these tumors] derive a significant benefit from adjuvant chemotherapy. These findings reinforce the notion that biology and tumor burden must be used together to guide treatment decisions in breast cancer.”
The subset analysis of MINDACT presented by Dr. Tryfonidis evaluated chemotherapy in 826 patients with small breast tumors (under < 1 cm) stratified by clinical risk according to the Adjuvant! Online prediction tool (modified version) and genomic recurrence risk according to MammaPrint (ie, clinical low risk or clinical high risk, genomic low risk or genomic high risk).
About three-quarters (75.5%) were found to be both of clinical and genomic low risks (concordant), whereas 24% were clinical low risk/genomic high risk (discordant). Discordant patients were randomized to receive chemotherapy or no chemotherapy. Few patients who received chemotherapy had recurrences, and they had high rates of overall, distant metastasis–free, and disease-free survival.
Looking at results of concordant patients (clinical low/genomic low) vs discordant patients with small vs larger tumors (ie, < 1 cm vs ≥ 1 cm), distant metastasis-free survival at 5 years was 98.1% vs 94.5%, respectively; 5-year disease-free survival was 92.3% vs 88.6%; and 5-year overall survival was 98.6% vs 97.2%. All the confidence intervals overlapped (number of observed events was small), Dr. Tryfonidis said.
Among discordant patients who received chemotherapy, 5-year overall survival was 98.5%, compared with 95.8% for those who did not receive chemotherapy. “We did not see this in concordant patients,” he said. Among discordant patients, 5-year distant metastasis–free survival was 97.3% for those who received chemotherapy and 91.3% for those who did not. The 5-year disease-free survival rate was 92.3% vs 84.5%, respectively. “These results indicate that almost a quarter of patients with node-negative small tumors may derive benefit from chemotherapy,” he stated. ■
DISCLOSURE: Drs. Tryfonidis and Cardoso reported no conflicts of interest.
1. Tryfonidis K, et al: Results from an EORTC 10041/BIG 3-04 (MINDACT) trial substudy. ESMO 2017 Congress. Abstract 150O_PR. Presented September 8, 2017.
2. Cardoso F, van’t Leer LJ, Bogaerts J, et al: 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 375:717-729, 2016.
Hope S. Rugo, MD
The Formal discussant of this presentation, Hope S. Rugo, MD, of the University of California, San Francisco, said, “Tailoring treatment to biology results in incremental improvements in outcome.”
She continued: “This analysis gives us excellent data on the natural history...!-->!-->