Outcome prediction by the 70-gene profile in the context of the National Comprehensive Cancer Network (NCCN) guidelines

Abstract

535 Background: According to the NCCN consensus guidelines molecular profiling for breast cancer prognosis may be used in patients with ER-positive, Her2-negative and LN-negative disease. Current proposed NCCN clinical risk assessment suggests adjuvant treatment for the majority of these patients. The 70-gene profile (MammaPrint) is validated as an independent prognostic indicator for patients with lymph node-negative and positive disease. Prognosis prediction by MammaPrint may be more suitable to indicate who needs adjuvant chemotherapy in addition to endocrine therapy. Methods: 566 tumor samples of women with ER-positive, Her2-negative and LN- negative breast cancer from 5 previously reported studies were analyzed and classified by MammaPrint as good or poor prognosis. 10-year breast cancer-specific survival (BCSS) was analyzed according to MammaPrint and the NCCN guidelines. Results: Median follow-up was 3.5 years (range 0.1–21.1). 380 of 566 patients (67%) were classified as good and 186 (33%) as poor prognosis by MammaPrint. Using the NCCN guidelines, 7% were classified as low and 93% as high risk respectively. 349 patients (62%) received no adjuvant treatment, 17% received hormonal treatment only, 2% chemotherapy only and 20% both respectively. At 10 years, BCSS was 91% vs. 67% for the good and poor prognosis groups (HR 4.0 [95%CI 2.0–7.9], p<0.001) whith MammaPrint risk assessment. If the NCCN guidelines were used, BCSS was 86% vs. 83% for the low and high risk groups (HR 1.11 [0.3–4.6), p=0.888). In multivariate analysis, adjusted for known prognostic factors and adjuvant therapy, only MammaPrint and histological grade were independent predictors for 10-year-BCSS with HRs of 2.8 (1.3–6.1, p=0.008) and 1.9 (1.1–3.1, p=0.015), respectively. Conclusions: MammaPrint is a strong and independent prognostic indicator in ER-positive, Her2-negative, LN-negative breast cancer and is discordant in 62% of cases when compared with the NCCN guidelines. MammaPrint identifies approximately 66% of NCCN high risk patients as having a good prognosis. Integration of MammaPrint into clinical risk assessment and adjuvant treatment selection can provide a large benefit for management of patients with endocrine-responsive early breast cancer. [Table: see text]