1. PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants
- Author
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Easton, Douglas, Antoniou, Antonis, Barnes, Daniel, Bolla, Manjeet, Leslie, Malgorzata, Dennis, Joseph, Wang, Qin, Muranen, Taru A [0000-0002-5895-1808], Khan, Sofia [0000-0003-4185-8882], Dennis, Joe [0000-0003-4591-1214], Keeman, Renske [0000-0002-5452-9933], Leslie, Goska [0000-0001-5756-6222], Parsons, Michael T [0000-0003-3242-8477], Ahearn, Thomas U [0000-0003-0771-7752], Andrulis, Irene L [0000-0002-4226-6435], Behrens, Sabine [0000-0002-9714-104X], Devilee, Peter [0000-0002-8023-2009], Evans, D Gareth [0000-0002-8482-5784], García-Closas, Montserrat [0000-0003-1033-2650], Izatt, Louise [0000-0003-1258-4843], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A [0000-0002-4361-4657], Lindeman, Geoffrey J [0000-0001-9386-2416], Neuhausen, Susan L [0000-0001-5053-0390], Newman, William G [0000-0002-6382-4678], Peterlongo, Paolo [0000-0001-6951-6855], Saloustros, Emmanouil [0000-0002-0485-0120], Suvanto, Maija [0000-0001-9271-7778], Tan, Yen Yen [0000-0003-1063-5352], Teixeira, Manuel R [0000-0002-4896-5982], Easton, Douglas F [0000-0003-2444-3247], Pharoah, Paul DP [0000-0001-8494-732X], Schmidt, Marjanka K [0000-0002-2228-429X], Nevanlinna, Heli [0000-0002-0916-2976], and Apollo - University of Cambridge Repository more...
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HEBON investigators - Abstract
2 We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 3 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators 4 of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). 5 PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier 6 patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished 7 clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by 8 PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but 9 the confidence intervals always included the calibration slope. Altogether, our results encourage the use of 10 the PREDICT ER-negative model in management of breast cancer patients with germline BRCA1 variants. 11 For the PREDICT ER-positive model, the discrimination was slightly lower in BRCA2 variant carriers 12 (concordance 0.60 in CIMBA, 0.65 in BCAC). Especially, inclusion of the tumor grade distorted the 13 prognostic estimates. The breast cancer mortality of BRCA2 carriers was under-estimated at the low end of 14 the PREDICT score distribution, whereas at the high end, the mortality was over-estimated. These data 15 suggest that BRCA2 status should also be taken into consideration with tumor characteristics, when 16 estimating the prognosis of ER-positive breast cancer patients. 17 Keywords: PREDICT, breast cancer, prognosis, BRCA1, BRCA2, validation, survival more...
- Published
- 2023