The University of Southampton
University of Southampton Institutional Repository

Pregnancies, breast-feeding, and breast cancer risk in the international BRCA1/2 carrier cohort study (IBCCS)

Pregnancies, breast-feeding, and breast cancer risk in the international BRCA1/2 carrier cohort study (IBCCS)
Pregnancies, breast-feeding, and breast cancer risk in the international BRCA1/2 carrier cohort study (IBCCS)
Multiparity, young age at first childbirth, and breast-feeding are associated with a reduced risk of breast cancer in the general population. The breast cancer predisposition gene, BRCA1, regulates normal cell differentiation. Because mammary gland cells divide and differentiate during pregnancy, reproductive factors may influence breast cancer risk in BRCA1/2 mutation carriers differently than they do in noncarriers. Methods: We performed a retrospective cohort study of 1601 women in the International BRCA1/2 Carrier Cohort Study cohort, all of whom carried a mutation in BRCA1 or BRCA2. Information on reproductive factors was obtained from a questionnaire. At the time of interview 853 subjects were classified with breast cancer. Data were analyzed by using a weighted cohort approach. All statistical tests were two-sided. Results: There was no statistically significant difference in the risk of breast cancer between parous and nulliparous women. Among parous women, an increasing number of full-term pregnancies was associated with a statistically significant decrease in the risk of breast cancer (P-trend =.008); risk was reduced by 14% (95% confidence interval [CI] = 6% to 22%) for each additional birth. This association was the same for carriers of mutations in either BRCA1 or BRCA2 and was restricted to women older than 40 years. In BRCA2 mutation carriers, first childbirth at later ages was associated with an increased risk of breast cancer compared with first childbirth before age 20 years (20-24 years, hazard ratio [HR] = 2.33 [95% CI = 0.93 to 5.83]; 25-29 years, HR = 2.68 [95% CI 1.02 to 7.07]; 30 years, HR = 1.97 [95% CI = 0.67 to 5.81]), whereas in BRCA1 mutation carriers, first childbirth at age 30 years or later was associated with a reduced risk of breast cancer compared with first childbirth before age 20 years (HR = 0.58 [95% CI = 0.36 to 0.94]). Neither history of interrupted pregnancies (induced abortions or miscarriage) nor history of breast-feeding was statistically significantly associated with the risk of breast cancer. Conclusions: BRCA1 and BRCA2 mutation carriers older than 40 years show a similar reduction in breast cancer risk with increasing parity as non-carriers.
risk, 2, women, cell, growth, penetrance, brca1, reproductive history, brca2, cancer, differentiation, mutation, estrogen-receptor, mutations, susceptibility, diagnosis, mutation carriers, gene
0027-8874
535-544
Andrieu, Nadine
bbf4cdb2-4f4a-435e-bc8d-8dda8dde9fd8
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Rookus, Matti
4a82efda-4af5-43fa-a584-91d5f8ab50d6
Brohet, Richard
1f557f20-9e33-403e-b9d6-47b8b151529d
Antoniou, Antonis C.
b5275276-df7e-42a4-9a38-6a9516924f0d
Peock, Susan
7e420471-9ee5-4a07-9536-bfdc4c6f1297
Evans, Gareth
ee001bc1-9b29-4a58-a251-a27b18eff669
Eccles, Diana
10d58972-8d94-4e46-b0c1-7cb17ea694c1
Douglas, Fiona
a35f2e38-4fc4-481e-a212-1e3ae5d5ae0c
Nogues, Catherine
2565f7f0-d985-4460-8b92-3a0429db3012
Gauthier-Villars, Marion
9bd0e9a5-aad3-4970-9ed0-1ca2e7c7ce2e
Chompret, Agnès
9a007955-9e07-43ec-9576-702f177a2302
Van Leeuwen, Flora E.
89d7c75b-228f-4c71-828b-c92b5e5ae42e
Kluijt, Irma
a3b61cea-70f1-4dad-8bde-4e3e5504a2ad
Benitez, Javier
aaf768e0-3166-4656-a787-89512ca1828c
Arver, Brita
179b96e1-1740-455d-a2bc-8e4ad32fb887
Olah, Edith
f4ee7e40-b263-490e-96fc-84b98eb2ec20
Chang-Claude, Jenny
cf472d49-8420-41ff-8a38-b0148f0a7cae
EMBRACE, None
cad541aa-bac7-4777-a762-c2d679502afa
GENEPSO, None
5f0c78b4-953e-4a68-b337-75c1029bdc8d
GEO-HEBON, None
311b0be5-f138-43f9-b08f-39edead94787
IBCCS Collaborators, None
f25ea81f-d9c3-4413-aca1-47a74a94a5cc
Andrieu, Nadine
bbf4cdb2-4f4a-435e-bc8d-8dda8dde9fd8
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Rookus, Matti
4a82efda-4af5-43fa-a584-91d5f8ab50d6
Brohet, Richard
1f557f20-9e33-403e-b9d6-47b8b151529d
Antoniou, Antonis C.
b5275276-df7e-42a4-9a38-6a9516924f0d
Peock, Susan
7e420471-9ee5-4a07-9536-bfdc4c6f1297
Evans, Gareth
ee001bc1-9b29-4a58-a251-a27b18eff669
Eccles, Diana
10d58972-8d94-4e46-b0c1-7cb17ea694c1
Douglas, Fiona
a35f2e38-4fc4-481e-a212-1e3ae5d5ae0c
Nogues, Catherine
2565f7f0-d985-4460-8b92-3a0429db3012
Gauthier-Villars, Marion
9bd0e9a5-aad3-4970-9ed0-1ca2e7c7ce2e
Chompret, Agnès
9a007955-9e07-43ec-9576-702f177a2302
Van Leeuwen, Flora E.
89d7c75b-228f-4c71-828b-c92b5e5ae42e
Kluijt, Irma
a3b61cea-70f1-4dad-8bde-4e3e5504a2ad
Benitez, Javier
aaf768e0-3166-4656-a787-89512ca1828c
Arver, Brita
179b96e1-1740-455d-a2bc-8e4ad32fb887
Olah, Edith
f4ee7e40-b263-490e-96fc-84b98eb2ec20
Chang-Claude, Jenny
cf472d49-8420-41ff-8a38-b0148f0a7cae
EMBRACE, None
cad541aa-bac7-4777-a762-c2d679502afa
GENEPSO, None
5f0c78b4-953e-4a68-b337-75c1029bdc8d
GEO-HEBON, None
311b0be5-f138-43f9-b08f-39edead94787
IBCCS Collaborators, None
f25ea81f-d9c3-4413-aca1-47a74a94a5cc

Andrieu, Nadine, Goldgar, David E., Easton, Douglas F., Rookus, Matti, Brohet, Richard, Antoniou, Antonis C., Peock, Susan, Evans, Gareth, Eccles, Diana, Douglas, Fiona, Nogues, Catherine, Gauthier-Villars, Marion, Chompret, Agnès, Van Leeuwen, Flora E., Kluijt, Irma, Benitez, Javier, Arver, Brita, Olah, Edith, Chang-Claude, Jenny, EMBRACE, None, GENEPSO, None, GEO-HEBON, None and IBCCS Collaborators, None (2006) Pregnancies, breast-feeding, and breast cancer risk in the international BRCA1/2 carrier cohort study (IBCCS). JNCI Journal of the National Cancer Institute, 98 (8), 535-544. (doi:10.1093/jnci/djj132).

Record type: Article

Abstract

Multiparity, young age at first childbirth, and breast-feeding are associated with a reduced risk of breast cancer in the general population. The breast cancer predisposition gene, BRCA1, regulates normal cell differentiation. Because mammary gland cells divide and differentiate during pregnancy, reproductive factors may influence breast cancer risk in BRCA1/2 mutation carriers differently than they do in noncarriers. Methods: We performed a retrospective cohort study of 1601 women in the International BRCA1/2 Carrier Cohort Study cohort, all of whom carried a mutation in BRCA1 or BRCA2. Information on reproductive factors was obtained from a questionnaire. At the time of interview 853 subjects were classified with breast cancer. Data were analyzed by using a weighted cohort approach. All statistical tests were two-sided. Results: There was no statistically significant difference in the risk of breast cancer between parous and nulliparous women. Among parous women, an increasing number of full-term pregnancies was associated with a statistically significant decrease in the risk of breast cancer (P-trend =.008); risk was reduced by 14% (95% confidence interval [CI] = 6% to 22%) for each additional birth. This association was the same for carriers of mutations in either BRCA1 or BRCA2 and was restricted to women older than 40 years. In BRCA2 mutation carriers, first childbirth at later ages was associated with an increased risk of breast cancer compared with first childbirth before age 20 years (20-24 years, hazard ratio [HR] = 2.33 [95% CI = 0.93 to 5.83]; 25-29 years, HR = 2.68 [95% CI 1.02 to 7.07]; 30 years, HR = 1.97 [95% CI = 0.67 to 5.81]), whereas in BRCA1 mutation carriers, first childbirth at age 30 years or later was associated with a reduced risk of breast cancer compared with first childbirth before age 20 years (HR = 0.58 [95% CI = 0.36 to 0.94]). Neither history of interrupted pregnancies (induced abortions or miscarriage) nor history of breast-feeding was statistically significantly associated with the risk of breast cancer. Conclusions: BRCA1 and BRCA2 mutation carriers older than 40 years show a similar reduction in breast cancer risk with increasing parity as non-carriers.

Full text not available from this repository.

More information

Published date: April 2006
Keywords: risk, 2, women, cell, growth, penetrance, brca1, reproductive history, brca2, cancer, differentiation, mutation, estrogen-receptor, mutations, susceptibility, diagnosis, mutation carriers, gene

Identifiers

Local EPrints ID: 62671
URI: https://eprints.soton.ac.uk/id/eprint/62671
ISSN: 0027-8874
PURE UUID: ad8ea0b3-5230-4b65-b56e-650d1f7a9a20

Catalogue record

Date deposited: 11 Sep 2008
Last modified: 13 Mar 2019 20:27

Export record

Altmetrics

Contributors

Author: Nadine Andrieu
Author: David E. Goldgar
Author: Douglas F. Easton
Author: Matti Rookus
Author: Richard Brohet
Author: Antonis C. Antoniou
Author: Susan Peock
Author: Gareth Evans
Author: Diana Eccles
Author: Fiona Douglas
Author: Catherine Nogues
Author: Marion Gauthier-Villars
Author: Agnès Chompret
Author: Flora E. Van Leeuwen
Author: Irma Kluijt
Author: Javier Benitez
Author: Brita Arver
Author: Edith Olah
Author: Jenny Chang-Claude
Author: None EMBRACE
Author: None GENEPSO
Author: None GEO-HEBON
Author: None IBCCS Collaborators

University divisions

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 https://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.

×