Gene test identifies women with early breast cancer who can forgo chemotherapy

A multigene test identified women with early breast cancer at low risk for recurrence who were disease free at 5-year follow-up without adjuvant chemotherapy, according to updated results of the West German Study Group phase 3 PlanB trial presented at the 10th European Breast Cancer Conference.

These data provide strong evidence for the implementation of the 21-gene Recurrence Score test (Oncotype DX) into clinical guidelines, according to Oleg Gluz, MD, of the West German Study Group in Monchengladbach, Germany, and colleagues.

The test — which takes between 8 and 10 days to complete — analyzes 21 genes that may affect progression of breast cancer and patient response to treatment. Scores range from 0 to 100 and, for the purpose of this trial, researchers considered a score of 11 or less low risk for recurrence, even if patients had high-risk nodal status, grade, tumor size or age.

The phase 3 PlanB trial is the first to use the 21-gene Recurrence Score test to assess survival.

The analysis included data from 3,198 patients (median age, 56 years) with early hormone receptor-positive or HER-2–negative breast cancer. Overall, 41.1% of patients had node-positive and 32.5% had grade 3 disease.

Three hundred forty-eight patients (15.3%) had a recurrence score of 11 or less and received antihormonal therapy without adjuvant chemotherapy.

Researchers considered women to be at intermediate or high risk for recurrence if they had a recurrence score of 12 or more (high risk, recurrence score of 25 or more), had more than four involved lymph nodes or had hormone receptor-negative disease. These women were randomly assigned to receive six cycles of docetaxel/cyclophosphamide or four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel.

Gluz and colleagues previously reported 3-year follow-up results of a planned interim analysis which showed a significant difference between central and local grade, Ki67 and recurrence score.

The current analysis evaluates 5-year outcome data. DFS — defined by invasive or noninvasive relapse, secondary malignancy or death — served as the primary endpoint.

Overall, 94% of patients in the low-risk cohort achieved 5-year DFS. Further, 94% of women in the intermediate-risk cohort and 84% of high-risk women achieved 5-year DFS (P<.001).

The test appeared to be a better independent predictor of disease recurrence than odal status, tumor size/grade and Ki67 protein alone, according to the researchers.

“In this prospective trial for patients who had a clinically determined intermediate- or high-risk of recurrence and who had 0-3 lymph nodes involved, we have been able to identify about 15% who were assessed by the 21-gene test as being at low genomic risk,” Gluz said in a press release. “Our data clearly reveal a stronger prognostic impact of recurrence score compared to immunohistochemical tools, such as Ki67 and hormone-receptor expression, and thus support the incorporation of the test, in combination with nodal status, grade and tumor size, into routine clinical practice for making treatment decisions for these patients.”

The researchers plan to extend the follow-up to 10 years in the WSG-ADAPT trial, which has already enrolled more than 4,000 patients. Researchers seek to evaluate combining the recurrence score with the assessment of early response to short-term preoperative antihormonal therapy as indicated by a decrease in the Ki67 protein.

“The combination of both tools may help to omit adjuvant chemotherapy in about 50% to 60% of early breast cancer patients,” Gluz said. “Final survival results of this study will be available in 2021.” – by Jennifer Southall

Reference: Gluz O, et al. Abstract 8LBA. Presented at: 10th European Breast Cancer Conference; March 9-11, 2016; Amsterdam.

Disclosure: The researchers report no relevant financial disclosures.