The 21-gene recurrence score (obtained with Oncotype DX) can help identify patients with estrogen receptor (ER)-positive, node-positive breast cancer who do not respond well to adjuvant chemoendocrine therapy, according to a retrospective analysis of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 study presented at the 2012 Breast Cancer Symposium.1
“Our findings help to refine residual risk of recurrence in node-positive, estrogen receptor–positive patients, and may help tailor the extent of adjuvant chemotherapy. These data may also identify appropriate candidates for clinical research protocols evaluating new adjuvant treatments,” said lead investigator Eleftherios P. Mamounas, MD, of Aultman Cancer Center in Canton, Ohio.
Of course, the recurrence score has been related to outcomes in several patient populations already, but most data are from estrogen receptor–positive node-negative patients. The current study shows that “we can apply those findings to ER-positive patients with any number of positive nodes, treated with chemotherapy as well as endocrine therapy, and find that the recurrence score is still prognostic across the spectrum,” he said.
Oncotype DX is currently indicated for use in patients with estrogen receptor–positive, node-negative breast cancer to determine prognosis and estimate whether the addition of chemotherapy to endocrine therapy would be beneficial. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines extend this recommendation to patients with micrometastases in the sentinel node.
The study included 1,065 patients treated with adjuvant doxorubicin/cyclophosphamide (AC) with or without paclitaxel plus adjuvant tamoxifen in the randomized NSABP B-28 trial. Researchers calculated recurrence score using tissue specimens from past breast surgeries and then correlated the score with outcomes. Median follow-up was 11.2 years.
Recurrence score was shown to be low (< 18) in 36%, intermediate (18–30) in 34%, and high (≥ 31%) in 30% of patients. The distribution of the recurrence score was not statistically significantly different by treatment, type of surgery, or number of positive nodes. However, older patients and patients with small tumors were significantly more likely to have a low recurrence score.
Independent Predictor of Outcomes
In the univariate analysis, the recurrence score was a significant predictor of disease-free survival, distant recurrence–free interval, breast cancer–specific survival, and overall survival. In multivariate analysis, the recurrence score provided independent prognostic information for all three endpoints beyond clinical and pathologic factors, including treatment, age, tumor size, tumor grade, number of positive nodes, and type of surgery (P < .001), Dr. Mamounas reported.
“The recurrence score was a significant predictor. For patients with a low score, disease-free survival at 10 years was close to 76%, while it dropped to 48% for those with a high score,” he said. “More importantly, overall survival was 90% for the low recurrence score group, vs 63% for the high recurrence score patients,” he added.
“It is also interesting to note that patients with four or more positive nodes and a low recurrence score had better outcomes than those with one to three positive nodes and a high recurrence score,” he said. “And by treatment assignment, outcomes were very similar between treatment arms in patients with low recurrence score, with the benefit of paclitaxel seen mainly in the intermediate– and high–recurrence score groups.”
The hazard ratios for the prognostic impact of the recurrence score were 2.53 for disease-free survival, 2.42 for distant recurrence-free interval, 3.09 for overall survival, and 3.38 for breast cancer–specific survival, all highly significant (P < .001).
The recurrence score was strongly related to 10-year risks of recurrence, with disease-free survival events occurring in 54% of patients in the high end of the recurrence score group vs 17% of those in the low end of the recurrence score. Breast cancer–specific deaths occurred in 33% and 2%, respectively, Dr. Mamounas further reported.
In an exploratory analysis, the recurrence score remained an independent predictor of all outcomes in patients with HER2-negative/equivocal tumors. In this subgroup of 937 patients, patients with high vs low recurrence score had more than a sixfold increase in breast cancer–specific mortality (P < .001).
The recurrence score provides information regarding residual risk of recurrence after chemotherapy. Therefore, the study’s findings can potentially help in making treatment decisions, Dr. 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 clinical trials evaluating novel adjuvant therapies. On the other hand, patients with low residual risk may do well with shorter duration of chemotherapy and will not be the best candidates for such clinical trials.”
He suggested that for low-risk patients it might be sufficient to treat with four cycles of AC, rather than a full course of eight cycles, including a taxane, though this will require further confirmation. Existing data already suggest, he added, that low-risk patients may not benefit from chemotherapy at all, and this is being further tested in a prospective Southwest Oncology Group (SWOG) trial (RxPONDER). The NSABP B-28 analysis indicates that the extent of chemotherapy might be tailored according to the estimation of residual risk, he said. ■
Disclosure: Dr. Mamounas serves as consultant (advisory board) and speaker for Genomic Health, Inc.
1. Mamounas EP, Tang G, Paik S, et al: Prognostic impact of the 21-gene recurrence score on disease-free and overall survival of node-positive, ER-positive patients with breast cancer treated with adjuvant chemotherapy: Results from NSABP B-28. 2012 Breast Cancer Symposium. Abstract 1. Presented September 13, 2011.
Andrew D. Seidman, MD, of Memorial Sloan-Kettering Cancer Center, New York, said 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 ...