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; 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; Johanna Rantala; Karina Rønlund; HEBON Investigators

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, 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, Johanna Rantala, Karina Rønlund, HEBON Investigators

^*Corresponding author af dette arbejde

3 Citationer (Scopus)

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	Current Medical Literature. Breast Cancer
Vol/bind	9
Udgave nummer	1
Sider (fra-til)	37
ISSN	2374-4677
DOI	https://doi.org/10.1038/s41523-023-00546-x
Status	Udgivet - 12 maj 2023

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

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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., ... HEBON Investigators (2023). PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants. Current Medical Literature. Breast Cancer, 9(1), 37. Artikel 37. https://doi.org/10.1038/s41523-023-00546-x

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, 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 & HEBON Investigators 2023, 'PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants', Current Medical Literature. Breast Cancer, bind 9, nr. 1, 37, s. 37. https://doi.org/10.1038/s41523-023-00546-x

@article{47e54bdca50d4890ae5d2961bc65cd77,

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 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 Anne-Marie Gerdes 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 Kelly-Anne Phillips and Pujana, {Miquel Angel} and Johanna Rantala and Karina R{\o}nlund and {HEBON Investigators}",

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

year = "2023",

month = may,

day = "12",

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

language = "English",

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journal = "Current Medical Literature. Breast Cancer",

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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 - 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 - Rantala, Johanna

AU - Rønlund, Karina

AU - HEBON Investigators

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.

UR - http://www.scopus.com/inward/record.url?scp=85160095823&partnerID=8YFLogxK

U2 - 10.1038/s41523-023-00546-x

DO - 10.1038/s41523-023-00546-x

M3 - Journal article

C2 - 37173335

SN - 2374-4677

VL - 9

SP - 37

JO - Current Medical Literature. Breast Cancer

JF - Current Medical Literature. Breast Cancer

IS - 1

M1 - 37

ER -

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

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