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PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants.

Title: PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants.
Authors: Muranen, TA; Morra, A; Khan, S; Barnes, DR; Bolla, MK; Dennis, J; Keeman, R; Leslie, G; Parsons, MT; Wang, Q; Ahearn, TU; Aittomäki, K; Andrulis, IL; Arun, BK; Behrens, S; Bialkowska, K; Bojesen, SE; Camp, NJ; Chang-Claude, J; Czene, K; Devilee, P; HEBON investigators; Domchek, SM; Dunning, AM; Engel, C; Evans, DG; Gago-Dominguez, M; García-Closas, M; Gerdes, A-M; Glendon, G; Guénel, P; Hahnen, E; Hamann, U; Hanson, H; Hooning, MJ; Hoppe, R; Izatt, L; Jakubowska, A; James, PA; Kristensen, VN; Lalloo, F; Lindeman, GJ; Mannermaa, A; Margolin, S; Neuhausen, SL; Newman, WG; Peterlongo, P; Phillips, K-A; Pujana, MA; Rantala, J; Rønlund, K; Saloustros, E; Schmutzler, RK; Schneeweiss, A; Singer, CF; Suvanto, M; Tan, YY; Teixeira, MR; Thomassen, M; Tischkowitz, M; Tripathi, V; Wappenschmidt, B; Zhao, E; Easton, DF; Antoniou, AC; Chenevix-Trench, G; Pharoah, PDP; Schmidt, MK; Blomqvist, C; Nevanlinna, H
Publisher Information: NATURE PORTFOLIO
Publication Year: 2023
Collection: The Institute of Cancer Research (ICR): Publications Repository
Subject Terms: HEBON investigators
Subject Geographic: United States
Description: We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but the confidence intervals always included the calibration slope. Altogether, our results encourage the use of the PREDICT ER-negative model in management of breast cancer patients with germline BRCA1 variants. For the PREDICT ER-positive model, the discrimination was slightly lower in BRCA2 variant carriers (concordance 0.60 in CIMBA, 0.65 in BCAC). Especially, inclusion of the tumor grade distorted the prognostic estimates. The breast cancer mortality of BRCA2 carriers was underestimated at the low end of the PREDICT score distribution, whereas at the high end, the mortality was overestimated. These data suggest that BRCA2 status should also be taken into consideration with tumor characteristics, when estimating the prognosis of ER-positive breast cancer patients.
Document Type: article in journal/newspaper
File Description: Electronic; application/pdf
Language: English
ISSN: 2374-4677
Relation: ARTN 37; npj Breast Cancer, 2023, 9 (1), pp. 37 -; https://repository.icr.ac.uk/handle/internal/5941
Availability: https://repository.icr.ac.uk/handle/internal/5941
Rights: http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.637C19AD
Database: BASE