Expanded utility of the 21-gene recurrence score (RS) (Oncotype DX) was shown in a retrospective analysis reported at the American Society of Clinical Oncology 2012 Breast Cancer Symposium by investigators from the National Surgical Adjuvant Breast and Bowel Project (NSABP).1
The RS can help identify estrogen receptor (ER)-positive patients with any number of positive lymph nodes who will have residual disease after adjuvant chemotherapy, who might benefit from additional treatment, reported Eleftherios P. Mamounas, MD, of the Aultman Cancer Center in Canton, Ohio.
As such, the RS can help in making treatment decisions, Mamounas maintained. “We can identify patients with high residual risk in spite of receiving chemotherapy. We can try to find a better treatment for them or enroll them in a clinical trial. On the other hand, patients with low residual risk may do well with less treatment,” he said.
Such patients might be sufficiently treated with only 4 cycles of chemotherapy, rather than a full course of 8 cycles, including a taxane, he said. The NSABP B-28 analysis indicates that the extent of chemotherapy might be tailored according to the estimation of residual risk, he said.
Oncotype DX is currently approved for use in patients with ER-positive, node-negative breast cancer to estimate whether the addition of chemotherapy to endocrine therapy would be beneficial. The current study shows that the RS can also be applied to ER-positive patients with any number of positive nodes, treated with chemotherapy as well as endocrine therapy. In this population, the RS was prognostic across the spectrum of subgroups.
NSABP B-28 included 1065 patients treated with adjuvant endocrine therapy and anthracycline/cyclophosphamide with or without paclitaxel in the randomized NSABP B-28 trial. Researchers calculated RS using tissue specimens from past breast surgeries and then correlated the RS with outcomes. Median follow-up was 11.2 years.
Recurrence Score a Robust Independent Predictor of Outcomes
The RS was low (<18) in 36% of patients, intermediate (18-30) in 34%, and high (≥31%) in 30% of patients. In the univariate analysis, the RS was a significant predictor of disease-free survival, distant recurrence-free interval, breast cancer–specific survival, and overall survival. In multivariate analysis, the RS provided independent prognostic information for all 4 end points beyond clinical and pathologic factors, including treatment, age, tumor size, tumor grade, number of positive nodes, and type of surgery (P <.001), Mamounas reported.
For patients with a low RS, disease-free survival was close to 76%, while it dropped to 48% for those with a high RS. Overall survival was 90% for the low RS group, versus 63% for the high RS patients, he reported.
The RS was strongly related to a 10-year risk of recurrence, with events occurring in 54% of patients in the high RS group versus 17% of those with low RS. Breast cancer–specific deaths occurred in 33% and 2%, respectively.
By treatment assignment, outcomes were very similar between treatment arms in patients with low RS, with the benefit of paclitaxel seen mainly in the intermediate and high RS groups.
Andrew Seidman, MD, of Memorial Sloan-Kettering Cancer Center, New York, said at a press briefing that the study “highlights the fact that despite hormone receptor positivity and HER2 negativity, many patients will have a high risk of recurrence despite receiving chemotherapy and appropriate endocrine therapy. This gene assay represents a biological tool that may be useful in the future in stratifying patients for clinical trials and in identifying candidates whose outcomes can be improved.”
- Mamounas EP, Tang G, Paik S, et al. Prognostic impact of the 21-gene recurrence score (RS) on disease-free and overall survival of node-positive, ER-positive breast cancer patients treated with adjuvant chemotherapy: results from NSABP B-28. Presented at: American Society of Clinical Oncology 2012 Breast Cancer Symposium; September 13-15, 2012; San Francisco, CA. Abstract 1.