Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

KConFab investigators; HEBON Investigators; SWE-BRCA Investigators

doi:10.1038/s41523-020-00185-6

Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

KConFab investigators, HEBON Investigators, SWE-BRCA Investigators

Research output: Contribution to journal › Article › peer-review

Abstract

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10⁻⁹). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

Original language	English (US)
Article number	44
Journal	npj Breast Cancer
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41523-020-00185-6
State	Published - Dec 1 2020

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Pharmacology (medical)

Access to Document

10.1038/s41523-020-00185-6

Cite this

@article{4ba44be92a4f4c318a76866f96e33cb5,

title = "Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer",

abstract = "Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10−9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.",

author = "{KConFab investigators} and {HEBON Investigators} and {SWE-BRCA Investigators} and Muranen, {Taru A.} and Sofia Khan and Rainer Fagerholm and Kristiina Aittom{\"a}ki and Cunningham, {Julie M.} and Joe Dennis and Goska Leslie and Lesley McGuffog and Parsons, {Michael T.} and Jacques Simard and Susan Slager and Penny Soucy and Easton, {Douglas F.} and Marc Tischkowitz and Spurdle, {Amanda B.} and Schmutzler, {Rita K.} and Barbara Wappenschmidt and Eric Hahnen and Hooning, {Maartje J.} and Singer, {Christian F.} and Gabriel Wagner and Mads Thomassen and Pedersen, {Inge Sokilde} and Domchek, {Susan M.} and Nathanson, {Katherine L.} and Conxi Lazaro and Rossing, {Caroline Maria} and Andrulis, {Irene L.} and Teixeira, {Manuel R.} and Paul James and Judy Garber and Weitzel, {Jeffrey N.} and Anna Jakubowska and Drakoulis Yannoukakos and John, {Esther M.} and Southey, {Melissa C.} and Schmidt, {Marjanka K.} and Antoniou, {Antonis C.} and Georgia Chenevix-Trench and Carl Blomqvist and Heli Nevanlinna",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41523-020-00185-6",

language = "English (US)",

volume = "6",

journal = "npj Breast Cancer",

issn = "2374-4677",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

AU - KConFab investigators

AU - HEBON Investigators

AU - SWE-BRCA Investigators

AU - Muranen, Taru A.

AU - Khan, Sofia

AU - Fagerholm, Rainer

AU - Aittomäki, Kristiina

AU - Cunningham, Julie M.

AU - Dennis, Joe

AU - Leslie, Goska

AU - McGuffog, Lesley

AU - Parsons, Michael T.

AU - Simard, Jacques

AU - Slager, Susan

AU - Soucy, Penny

AU - Easton, Douglas F.

AU - Tischkowitz, Marc

AU - Spurdle, Amanda B.

AU - Schmutzler, Rita K.

AU - Wappenschmidt, Barbara

AU - Hahnen, Eric

AU - Hooning, Maartje J.

AU - Singer, Christian F.

AU - Wagner, Gabriel

AU - Thomassen, Mads

AU - Pedersen, Inge Sokilde

AU - Domchek, Susan M.

AU - Nathanson, Katherine L.

AU - Lazaro, Conxi

AU - Rossing, Caroline Maria

AU - Andrulis, Irene L.

AU - Teixeira, Manuel R.

AU - James, Paul

AU - Garber, Judy

AU - Weitzel, Jeffrey N.

AU - Jakubowska, Anna

AU - Yannoukakos, Drakoulis

AU - John, Esther M.

AU - Southey, Melissa C.

AU - Schmidt, Marjanka K.

AU - Antoniou, Antonis C.

AU - Chenevix-Trench, Georgia

AU - Blomqvist, Carl

AU - Nevanlinna, Heli

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10−9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

AB - Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10−9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

UR - http://www.scopus.com/inward/record.url?scp=85090501112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85090501112&partnerID=8YFLogxK

U2 - 10.1038/s41523-020-00185-6

DO - 10.1038/s41523-020-00185-6

M3 - Article

AN - SCOPUS:85090501112

SN - 2374-4677

VL - 6

JO - npj Breast Cancer

JF - npj Breast Cancer

IS - 1

M1 - 44

ER -

Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this