Optimized outcome prediction in breast cancer by combining the 70-gene signature with clinical risk prediction algorithms

Abstract

Clinical guidelines for breast cancer treatment differ in their selection of patients at a high risk of recurrence who are eligible to receive adjuvant systemic treatment (AST). The 70-gene signature is a molecular tool to better guide AST decisions. The aim of this study was to evaluate whether adding the 70-gene signature to clinical risk prediction algorithms can optimize outcome prediction and consequently treatment decisions in early stage, node-negative breast cancer patients. A 70-gene signature was available for 427 patients participating in the RASTER study (cT1-3N0M0). Median follow-up was 61.6 months. Based on 5-year distant-recurrence free interval (DRFI) probabilities survival areas under the curve (AUC) were calculated and compared for risk estimations based on the six clinical risk prediction algorithms: Adjuvant! Online (AOL), Nottingham Prognostic Index (NPI), St. Gallen (2003), the Dutch National guidelines (CBO 2004 and NABON 2012), and PREDICT plus. Also, survival AUC were calculated after adding the 70-gene signature to these clinical risk estimations. Systemically untreated patients with a high clinical risk estimation but a low risk 70-gene signature had an excellent 5-year DRFI varying between 97.1 and 100 %, depending on the clinical risk prediction algorithms used in the comparison. The best risk estimation was obtained in this cohort by adding the 70-gene signature to CBO 2012 (AUC: 0.644) and PREDICT (AUC: 0.662). Clinical risk estimations by all clinical algorithms improved by adding the 70-gene signature. Patients with a low risk 70-gene signature have an excellent survival, independent of their clinical risk estimation. Adding the 70-gene signature to clinical risk prediction algorithms improves risk estimations and therefore might improve the identification of early stage node-negative breast cancer patients for whom AST has limited value. In this cohort, the PREDICT plus tool in combination with the 70-gene signature provided the best risk prediction.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-014-2954-2) contains supplementary material, which is available to authorized users.

Prognostic contribution of mammographic breast density and HER2 overexpression to the Nottingham Prognostic Index in patients with invasive breast cancer

“…Multigene signatures associated with prognosis have recently emerged and some are even commercially available [36]. Drukker et al [37] showed a prognostic benefit by combining the 70-gene signature with the classical scoring systems. Nevertheless, these gene signatures carry many shortcomings, different multigene tests give different and variating results making their implementation into clinical practice difficult [38, 39].…”

Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study

“…Online tool, PREDICT incorporates HER2 status in its model. 18 After completion of CRF1, the tumor samples were sent for 70-GS analysis, and the results were disclosed to the oncologist within 10 working days. The posttest CT recommendation and the actually administered CT were recorded in a second CRF (CRF2).…”

Computer-aided prognosis on breast cancer with hematoxylin and eosin histopathology images: A review

“…21 Over the past decade, molecular taxonomy has revealed molecular heterogeneity of BC and has been shown to provide more accurate prognostic information. [22][23][24] But the actual role of molecular techniques in clinical practice is limited by their availability. 20 Thus, BC management relies largely on inexpensive and routine morphological assessment of H&E images coupled with biomarker semi-quantification of IHC images.…”