The University of Southampton
University of Southampton Institutional Repository

Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing

Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing
Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing

Background: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. Methods: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium(TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. Results: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. Conclusions: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.

0027-8874
855-862
Shimelis, Hermela
f7a16799-6468-47bf-aeef-63e6cacc594b
LaDuca, Holly
55475e7b-5d37-4b23-b081-bdffb6065011
Hu, Chunling
af689226-1e50-462e-9ded-726fa1671959
Hart, Steven N.
44520820-8c6f-4213-a806-4db36e64296d
Na, Jie
650aff52-9592-43bd-be76-e23294445226
Thomas, Abigail
b9bac0f7-3427-4dcf-8b7f-6da3f7132b27
Akinhanmi, Margaret
43f34dcf-8295-4d69-a17e-eafa9faaa735
Moore, Raymond M.
57531ff7-1b12-4799-9025-9a4e39b00d79
Brauch, Hiltrud
4c169b29-0f80-4453-a939-6634912e6f31
Cox, Angela
41fd94c3-79a2-49d4-bda0-616488b147da
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Ewart-Toland, Amanda
8ef95576-249e-496c-8d8f-8931e2cc2c4c
Fasching, Peter A.
28905b56-c431-479b-8687-98d5858e04e9
Fostira, Florentia
1f0f12ed-ce22-45ec-b5dc-59e66e63c5d4
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Godwin, Andrew K.
a7e89dce-59e1-48f7-b668-42777f362435
Konstantopoulou, Irene
39dc052d-18ab-479a-abe2-7465b5727c1d
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Sharma, Priyanka
aa5b0a3c-9f30-4933-b57f-1d100f20f55a
Yannoukakos, Drakoulis
b3f8728f-9538-4b45-84b1-dfe08bb0d3b8
Yao, Song
1a5e966b-4529-466c-b1b2-2bcfcb23d599
Feng, Bing Jian
b06d35c2-9612-427d-a5c2-0f14abbc9b45
Davis, Brigette Tippin
92f8fab8-9e48-4df1-bc1c-42e3929fcf44
Lilyquist, Jenna
115fe0ff-0f64-4260-b1d7-633c18199311
Pesaran, Tina
f5b30177-f11e-4c14-95fe-e23b663c5867
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Polley, Eric C.
b9046fe3-e109-41db-b05a-728f79e1645c
Dolinsky, Jill S.
434b8b2e-b96e-440d-a1b1-fb86e52f234a
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a
Shimelis, Hermela
f7a16799-6468-47bf-aeef-63e6cacc594b
LaDuca, Holly
55475e7b-5d37-4b23-b081-bdffb6065011
Hu, Chunling
af689226-1e50-462e-9ded-726fa1671959
Hart, Steven N.
44520820-8c6f-4213-a806-4db36e64296d
Na, Jie
650aff52-9592-43bd-be76-e23294445226
Thomas, Abigail
b9bac0f7-3427-4dcf-8b7f-6da3f7132b27
Akinhanmi, Margaret
43f34dcf-8295-4d69-a17e-eafa9faaa735
Moore, Raymond M.
57531ff7-1b12-4799-9025-9a4e39b00d79
Brauch, Hiltrud
4c169b29-0f80-4453-a939-6634912e6f31
Cox, Angela
41fd94c3-79a2-49d4-bda0-616488b147da
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Ewart-Toland, Amanda
8ef95576-249e-496c-8d8f-8931e2cc2c4c
Fasching, Peter A.
28905b56-c431-479b-8687-98d5858e04e9
Fostira, Florentia
1f0f12ed-ce22-45ec-b5dc-59e66e63c5d4
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Godwin, Andrew K.
a7e89dce-59e1-48f7-b668-42777f362435
Konstantopoulou, Irene
39dc052d-18ab-479a-abe2-7465b5727c1d
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Sharma, Priyanka
aa5b0a3c-9f30-4933-b57f-1d100f20f55a
Yannoukakos, Drakoulis
b3f8728f-9538-4b45-84b1-dfe08bb0d3b8
Yao, Song
1a5e966b-4529-466c-b1b2-2bcfcb23d599
Feng, Bing Jian
b06d35c2-9612-427d-a5c2-0f14abbc9b45
Davis, Brigette Tippin
92f8fab8-9e48-4df1-bc1c-42e3929fcf44
Lilyquist, Jenna
115fe0ff-0f64-4260-b1d7-633c18199311
Pesaran, Tina
f5b30177-f11e-4c14-95fe-e23b663c5867
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Polley, Eric C.
b9046fe3-e109-41db-b05a-728f79e1645c
Dolinsky, Jill S.
434b8b2e-b96e-440d-a1b1-fb86e52f234a
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a

Shimelis, Hermela, LaDuca, Holly, Hu, Chunling, Hart, Steven N., Na, Jie, Thomas, Abigail, Akinhanmi, Margaret, Moore, Raymond M., Brauch, Hiltrud, Cox, Angela, Eccles, Diana M., Ewart-Toland, Amanda, Fasching, Peter A., Fostira, Florentia, Garber, Judy, Godwin, Andrew K., Konstantopoulou, Irene, Nevanlinna, Heli, Sharma, Priyanka, Yannoukakos, Drakoulis, Yao, Song, Feng, Bing Jian, Davis, Brigette Tippin, Lilyquist, Jenna, Pesaran, Tina, Goldgar, David E., Polley, Eric C., Dolinsky, Jill S. and Couch, Fergus J. (2018) Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing. Journal of the National Cancer Institute, 110 (8), 855-862. (doi:10.1093/jnci/djy106).

Record type: Article

Abstract

Background: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. Methods: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium(TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. Results: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. Conclusions: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.

Text
djy106 - Version of Record
Download (765kB)

More information

Accepted/In Press date: 11 May 2018
e-pub ahead of print date: 7 August 2018

Identifiers

Local EPrints ID: 426063
URI: http://eprints.soton.ac.uk/id/eprint/426063
ISSN: 0027-8874
PURE UUID: be7e4a1a-d654-472d-bb2a-5c861f71b068
ORCID for Diana M. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 12 Nov 2018 17:30
Last modified: 16 Mar 2024 02:39

Export record

Altmetrics

Contributors

Author: Hermela Shimelis
Author: Holly LaDuca
Author: Chunling Hu
Author: Steven N. Hart
Author: Jie Na
Author: Abigail Thomas
Author: Margaret Akinhanmi
Author: Raymond M. Moore
Author: Hiltrud Brauch
Author: Angela Cox
Author: Diana M. Eccles ORCID iD
Author: Amanda Ewart-Toland
Author: Peter A. Fasching
Author: Florentia Fostira
Author: Judy Garber
Author: Andrew K. Godwin
Author: Irene Konstantopoulou
Author: Heli Nevanlinna
Author: Priyanka Sharma
Author: Drakoulis Yannoukakos
Author: Song Yao
Author: Bing Jian Feng
Author: Brigette Tippin Davis
Author: Jenna Lilyquist
Author: Tina Pesaran
Author: David E. Goldgar
Author: Eric C. Polley
Author: Jill S. Dolinsky
Author: Fergus J. Couch

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×