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

Taru A. Muranen; Anna Morra; Sofia Khan; Daniel R. Barnes; Manjeet K. Bolla; Joe Dennis; Renske Keeman; Goska Leslie; Michael T. Parsons; Qin Wang; Thomas U. Ahearn; Kristiina Aittomäki; Irene L. Andrulis; Banu K. Arun; Sabine Behrens; Katarzyna Bialkowska; Stig E. Bojesen; Nicola J. Camp; Jenny Chang-Claude; Kamila Czene; Peter Devilee; HEBON Investigators; Susan M. Domchek; Alison M. Dunning; Christoph Engel; D. Gareth Evans; Manuela Gago-Dominguez; Montserrat García-Closas; Anne Marie Gerdes; Gord Glendon; Pascal Guénel; Eric Hahnen; Ute Hamann; Helen Hanson; Maartje J. Hooning; Reiner Hoppe; Louise Izatt; Anna Jakubowska; Paul A. James; Vessela N. Kristensen; Fiona Lalloo; Geoffrey J. Lindeman; Arto Mannermaa; Sara Margolin; Susan L. Neuhausen; William G. Newman; Paolo Peterlongo; Kelly Anne Phillips; Miquel Angel Pujana; Karina Rønlund; Mads Thomassen

doi:10.1038/s41523-023-00546-x

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

Taru A. Muranen^*, Anna Morra, Sofia Khan, Daniel R. Barnes, Manjeet K. Bolla, Joe Dennis, Renske Keeman, Goska Leslie, Michael T. Parsons, Qin Wang, Thomas U. Ahearn, Kristiina Aittomäki, Irene L. Andrulis, Banu K. Arun, Sabine Behrens, Katarzyna Bialkowska, Stig E. Bojesen, Nicola J. Camp, Jenny Chang-Claude, Kamila CzenePeter Devilee, HEBON Investigators, Susan M. Domchek, Alison M. Dunning, Christoph Engel, D. Gareth Evans, Manuela Gago-Dominguez, Montserrat García-Closas, Anne Marie Gerdes, Gord Glendon, Pascal Guénel, Eric Hahnen, Ute Hamann, Helen Hanson, Maartje J. Hooning, Reiner Hoppe, Louise Izatt, Anna Jakubowska, Paul A. James, Vessela N. Kristensen, Fiona Lalloo, Geoffrey J. Lindeman, Arto Mannermaa, Sara Margolin, Susan L. Neuhausen, William G. Newman, Paolo Peterlongo, Kelly Anne Phillips, Miquel Angel Pujana, Karina Rønlund, Mads Thomassen

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

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.

Originalsprog	Engelsk
Artikelnummer	37
Tidsskrift	npj Breast Cancer
Vol/bind	9
Antal sider	15
ISSN	2374-4677
DOI	https://doi.org/10.1038/s41523-023-00546-x
Status	Udgivet - 12. maj 2023

Bibliografisk note

Funding Information:
We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. BCAC is funded by the European Union Horizon 2020 Research and Innovation Programme (grant number 634935), and the PERSPECTIVE project, funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministère de l’Économie et de Innovation du Québec through Genome Québec, the Quebec Breast Cancer Foundation. The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Additional funding for BCAC is provided via the Confluence project which is funded with intramural funds from the National Cancer Institute Intramural Research Program, National Institutes of Health. The BRIDGES panel sequencing was supported by the European Union Horizon 2020 research and innovation program BRIDGES (grant number, 634935) and the Wellcome Trust (v203477/Z/16/Z). HEBCS (T.A.M. and H.Ne.) was funded by the Helsinki University Hospital Research Fund, the Sigrid Jusélius Foundation, and the Cancer Foundation Finland. Detailed acknowledgements of individual studies with funding information are provided in Supplementary Note .

Publisher Copyright:
© 2023, The Author(s).

Dokumenter og links

10.1038/s41523-023-00546-xLicens: CC BY

Open Access VersionForlagets udgivne version, 1,22 MBLicens: CC BY

Citationsformater

Muranen, T. A., Morra, A., Khan, S., Barnes, D. R., Bolla, M. K., Dennis, J., Keeman, R., Leslie, G., Parsons, M. T., Wang, Q., Ahearn, T. U., Aittomäki, K., Andrulis, I. L., Arun, B. K., Behrens, S., Bialkowska, K., Bojesen, S. E., Camp, N. J., Chang-Claude, J., ... Thomassen, M. (2023). PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants. npj Breast Cancer, 9, Artikel 37. https://doi.org/10.1038/s41523-023-00546-x

@article{6e1a488015aa433c80cc5af116208968,

title = "PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants",

abstract = "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 (G{\"o}nen & 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.",

author = "Muranen, {Taru A.} and Anna Morra and Sofia Khan and Barnes, {Daniel R.} and Bolla, {Manjeet K.} and Joe Dennis and Renske Keeman and Goska Leslie and Parsons, {Michael T.} and Qin Wang and Ahearn, {Thomas U.} and Kristiina Aittom{\"a}ki and Andrulis, {Irene L.} and Arun, {Banu K.} and Sabine Behrens and Katarzyna Bialkowska and Bojesen, {Stig E.} and Camp, {Nicola J.} and Jenny Chang-Claude and Kamila Czene and Peter Devilee and {HEBON Investigators} and Domchek, {Susan M.} and Dunning, {Alison M.} and Christoph Engel and Evans, {D. Gareth} and Manuela Gago-Dominguez and Montserrat Garc{\'i}a-Closas and Gerdes, {Anne Marie} and Gord Glendon and Pascal Gu{\'e}nel and Eric Hahnen and Ute Hamann and Helen Hanson and Hooning, {Maartje J.} and Reiner Hoppe and Louise Izatt and Anna Jakubowska and James, {Paul A.} and Kristensen, {Vessela N.} and Fiona Lalloo and Lindeman, {Geoffrey J.} and Arto Mannermaa and Sara Margolin and Neuhausen, {Susan L.} and Newman, {William G.} and Paolo Peterlongo and Phillips, {Kelly Anne} and Pujana, {Miquel Angel} and Karina R{\o}nlund and Mads Thomassen",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

day = "12",

doi = "10.1038/s41523-023-00546-x",

language = "English",

volume = "9",

journal = "npj Breast Cancer",

issn = "2374-4677",

publisher = "Nature Publishing Group",

}

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, AM, 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, KA, Pujana, MA, Rønlund, K & Thomassen, M 2023, 'PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants', npj Breast Cancer, bind 9, 37. https://doi.org/10.1038/s41523-023-00546-x

TY - JOUR

T1 - PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants

AU - Muranen, Taru A.

AU - Morra, Anna

AU - Khan, Sofia

AU - Barnes, Daniel R.

AU - Bolla, Manjeet K.

AU - Dennis, Joe

AU - Keeman, Renske

AU - Leslie, Goska

AU - Parsons, Michael T.

AU - Wang, Qin

AU - Ahearn, Thomas U.

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L.

AU - Arun, Banu K.

AU - Behrens, Sabine

AU - Bialkowska, Katarzyna

AU - Bojesen, Stig E.

AU - Camp, Nicola J.

AU - Chang-Claude, Jenny

AU - Czene, Kamila

AU - Devilee, Peter

AU - HEBON Investigators

AU - Domchek, Susan M.

AU - Dunning, Alison M.

AU - Engel, Christoph

AU - Evans, D. Gareth

AU - Gago-Dominguez, Manuela

AU - García-Closas, Montserrat

AU - Gerdes, Anne Marie

AU - Glendon, Gord

AU - Guénel, Pascal

AU - Hahnen, Eric

AU - Hamann, Ute

AU - Hanson, Helen

AU - Hooning, Maartje J.

AU - Hoppe, Reiner

AU - Izatt, Louise

AU - Jakubowska, Anna

AU - James, Paul A.

AU - Kristensen, Vessela N.

AU - Lalloo, Fiona

AU - Lindeman, Geoffrey J.

AU - Mannermaa, Arto

AU - Margolin, Sara

AU - Neuhausen, Susan L.

AU - Newman, William G.

AU - Peterlongo, Paolo

AU - Phillips, Kelly Anne

AU - Pujana, Miquel Angel

AU - Rønlund, Karina

AU - Thomassen, Mads

PY - 2023/5/12

Y1 - 2023/5/12

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 (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.

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 (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.

U2 - 10.1038/s41523-023-00546-x

DO - 10.1038/s41523-023-00546-x

M3 - Journal article

C2 - 37173335

AN - SCOPUS:85160095823

SN - 2374-4677

VL - 9

JO - npj Breast Cancer

JF - npj Breast Cancer

M1 - 37

ER -

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

Abstract

Bibliografisk note

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