Evaluation of the 70-gene prognosis MammaPrint signature for the prediction of prognosis of breast cancer independently from histologic grade.

Abstract

561 Background: Histologic grade is one of the strongest prognostic factors for breast cancer patients. In this study we assessed the prognostic value of the 70-gene prognosis signature (MammaPrint), validated for node-negative and -positive patients, for grade (G) 1-3 breast cancer. Methods: 1630 tumor samples of pT1-3 N0-1 breast cancer patients from 7 previously reported studies were analyzed and classified by MammaPrint as low or high risk. 10-year breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) was analyzed using Kaplan-Meier survival curves and multivariate Cox regression analyses. Results: Of 1,630 patients 392 (24%) were classified as G1 (21% 70-gene high risk), 646 (40%) as G2 (42% high risk) and 592 (36%) as G3 (86% high risk), respectively. At 10 years of follow-up, the 70-gene signature accurately distinguished low-risk from high-risk tumors for all histologic grades: within G1 tumors, absolute BCSS was 91% for 70-gene low risk and 82% for 70-gene high risk patients, HR 2.6 (95%CI 1.1-5.7), p = 0.02. Within G2 survival was 88% (low risk) and 68% (high risk), HR 3.3 (2.1-5.3), p < 0.01 and within G3 survival was 86% (low risk) and 64% (high risk), HR 3.4 (1.6- 7.2), p < 0.01. For DDFS: G1 HR 2.8 (1.5-5.4), p < 0.01), G2 HR 2.2 (1.5-3.2), p < 0.01 and G3 HR 2.4 (1.3-4.5), p < 0.01. Multivariate analysis with known prognostic factors and adjuvant therapy including histologic grade and the signature confirmed MammaPrint as strongest independent prognostic factor for 10-year survival (HR BCSS 2.8 [1.8-4.3], p < 0.01) and DDFS HR 2.2 [1.5-3.2], p < 0.01). Limited to chemotherapy-untreated patients only, results were similar (multivariate HR BCSS 2.3 [1.5-3.8], p < 0.01 and DDFS HR 1.9 [1.3-2.8], p < 0.01). Conclusions: The 70-gene MammaPrint signature provides independent prognostic information for all histological grades. Of note, “G1/70-gene high-risk” patients had a relatively poor 10-year BCSS of 82%, and therefore may be treated aggressively. In contrast, “G3/70-gene low-risk” patients achieved a 10-year BCSS of 86%, where adjuvant chemotherapy might be of limited benefit. This study confirms the clinical value of the 70-gene signature for all histological grades. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agendia Agendia