PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants
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PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants. / HEBON Investigators.
I: npj Breast Cancer, Bind 9, Nr. 1, 37, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants
AU - Muranen, Taru
AU - Morra, Anna
AU - Khan, Sofia R.
AU - Barnes, Daniel K.
AU - Bolla, Manjeet
AU - Dennis, Joe
AU - Keeman, Renske
AU - Leslie, Goska T.
AU - Parsons, Michael
AU - Wang, Qin U.
AU - Ahearn, Thomas
AU - Aittomaeki, Kristiina L.
AU - Andrulis, Irene K.
AU - Arun, Banu
AU - Behrens, Sabine
AU - Bialkowska, Katarzyna E.
AU - Bojesen, Stig J.
AU - Camp, Nicola
AU - Chang-Claude, Jenny
AU - Czene, Kamila
AU - Devilee, Peter M.
AU - Domchek, Susan M.
AU - Dunning, Alison
AU - Engel, Christoph
AU - Evans, D. Gareth
AU - Gago-Dominguez, Manuela
AU - Garcia-Closas, Montserrat
AU - Gerdes, Anne-Marie
AU - Glendon, Gord
AU - Guenel, Pascal
AU - Hahnen, Eric
AU - Hamann, Ute
AU - Hanson, Helen J.
AU - Hooning, Maartje
AU - Hoppe, Reiner
AU - Izatt, Louise
AU - Jakubowska, Anna A.
AU - James, Paul N.
AU - Kristensen, Vessela
AU - Lalloo, Fiona J.
AU - Lindeman, Geoffrey
AU - Mannermaa, Arto
AU - Margolin, Sara L.
AU - Neuhausen, Susan G.
AU - Newman, William
AU - Peterlongo, Paolo
AU - Phillips, Kelly-Anne
AU - Pujana, Miquel Angel
AU - Rantala, Johanna
AU - Ronlund, Karina
AU - HEBON Investigators
PY - 2023
Y1 - 2023
N2 - 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 (Gonen & 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.
AB - 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 (Gonen & 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.
KW - MODEL PREDICT
KW - SURVIVAL
KW - VALIDATION
KW - ADJUVANT
KW - OVARIAN
KW - WOMEN
KW - TOOL
U2 - 10.1038/s41523-023-00546-x
DO - 10.1038/s41523-023-00546-x
M3 - Journal article
C2 - 37173335
VL - 9
JO - npj Breast Cancer
JF - npj Breast Cancer
SN - 2374-4677
IS - 1
M1 - 37
ER -
ID: 347812897