Using a 70-gene signature test could identify many women with early-stage breast cancer considered to be at high clinical risk who do not actually need chemotherapy, according to a new study.
Women with early-stage breast cancer are often treated with adjuvant chemotherapy and other systemic therapies; treatment decisions are based on algorithms that consider tumor and patient characteristics. “However, these algorithms do not take into account the individual biologic characteristics of the patient’s tumor,” wrote study authors led by Fatima Cardoso, MD, of the Champalimaud Clinical Center in Lisbon.
Gene expression profiling has been used to distinguish high- and low-risk patients in previous studies. The new study used the MammaPrint 70-gene signature test to prospectively assess the clinical utility of such gene profiling in 6,693 women with early-stage breast cancer. The results were published in the New England Journal of Medicine; the primary goal was to assess outcomes in women deemed at high clinical risk but low genomic risk who did not undergo chemotherapy based on the gene-expression profile.
A total of 1,550 women (23.2%) were at high clinical risk but low genomic risk (1,806 patients were at high risk on both tests); these women were randomized to a chemotherapy or no-chemotherapy group on the basis of either the clinical or the genomic test result.
At 5 years, the rate of survival without distant metastasis was 94.7% for those patients who did not receive chemotherapy; this met the study’s primary endpoint of noninferiority compared with those who did receive adjuvant chemotherapy. The rate was 94.4% in the intention-to-treat population who did not receive chemotherapy (ie, underwent randomization based on genomic risk), compared with 95.9% for those who did receive chemotherapy (randomization based on clinical risk), for an adjusted hazard ratio of 0.78 (95% CI, 0.50–1.21; P = .27).
In the group of patients with low clinical risk but high genomic risk, the 5-year rates of survival without distant metastasis were again similar, at 95.8% in those who did receive chemotherapy (randomization based on genomic risk) and 95.0% for those who did not (randomization based on clinical risk). This suggests that using the genomic test to guide treatment in this group did not offer any advantage.
If the genomic signature was used to guide treatment in all women deemed at high risk clinically, but low risk genomically, 46.2% of patients might avoid chemotherapy. The study’s results were similar in subgroups of women with estrogen receptor–positive, HER2-negative tumors, and for those with node-negative disease or those who had one to three positive nodes.
“The addition of the 70-gene signature to the traditional clinical and pathological factors provided valuable information for considering which patients might benefit from adjuvant chemotherapy,” the authors concluded. “We found that chemotherapy with its attendant toxic effects could be avoided in these patients at high clinical risk but low genomic risk at a cost of a risk of distant metastasis at 5 years that is 1.5 percentage points higher.”