70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer

Abstract

BACKGROUNDThe 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODSIn this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. RESULTSA total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemother apy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. CONCLUSIONSAmong women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemo-

Molecular signatures in breast cancer

“…A supervised classification model was then generated after extensive feature selection these patients would ordinarily have been given chemotherapy, yet, since patients were classified as low-risk based on the gene signature, they were not given chemotherapy. The rate of 5-year survival was 94.7% in this clinically and genomic discordant risk group [51], suggesting that using the genomic risk predictor to identify low-risk patients might be clinically useful in recognising a target population that will have a good prognosis without chemotherapy, despite having contrary clinical indicators of high-risk disease.…”

Adjuvant ovarian suppression for resected breast cancer: 2017 critical assessment

“…Data on exactly how good are the outcomes for women with higher clinical risk profiles but favorable gene expression profiles on hormones alone are still awaited for the ONCOTYPE-DX (from studies called TAILOR-RX for node-negative women and RX-PONDER for those with 1-3 involved nodes). The MINDACT trial has reported a 5-year rate of death or distant metastases of 5.3% for women with high clinical risk but low genomic risk by the Mammaprint assay [24]. This DDFS is clearly worse than that observed in the ''no chemotherapy'' cohort of SOFT, but was improved by only 1.5% by adding chemotherapy.…”

15. Internationale St.-Gallen-Konsensus-Konferenz: Behandlung des frühen Mammakarzinoms

“…Im Anschluss an eine adjuvante Chemotherapie ist ein Aromatasehemmer grundsätzlich zu erwägen, wenn sicher eine permanent postmenopausale Situation vorliegt [1]. Auch für den MP-Score liegen erste prospektive Daten mit einem Followup von knapp 5 Jahren bei Patientinnen mit 1-3 befallenen Lymphknoten vor [3]. Anhand dieser noch vorläufigen Daten kann bei niedrigem Risikoprofil nach MP bei Patientinnen mit 1-3 befallenen Lymphknoten auf eine adjuvante Chemotherapie verzichtet werden.…”