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The influence of number and timing of pregnancies on breast cancer risk for women with BRCA1 or BRCA2 mutations

The influence of number and timing of pregnancies on breast cancer risk for women with BRCA1 or BRCA2 mutations
The influence of number and timing of pregnancies on breast cancer risk for women with BRCA1 or BRCA2 mutations
Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
1-13
Terry, Mary Beth
f4e42578-34d7-4e36-a71d-2c174d62b9c3
Liao, Yuyan
6ce57c37-c181-4a6a-9380-208aa78ae26a
Kast, Karin
7cde00f5-f897-4c84-bb86-2ecdd6e23b6d
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
et al.
EMBRACE
GENEPSO
BCFR
HEBON
kConFab
IBCCS
Terry, Mary Beth
f4e42578-34d7-4e36-a71d-2c174d62b9c3
Liao, Yuyan
6ce57c37-c181-4a6a-9380-208aa78ae26a
Kast, Karin
7cde00f5-f897-4c84-bb86-2ecdd6e23b6d
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23

Terry, Mary Beth, Liao, Yuyan and Kast, Karin , et al., EMBRACE, GENEPSO, BCFR, HEBON, kConFab and IBCCS (2019) The influence of number and timing of pregnancies on breast cancer risk for women with BRCA1 or BRCA2 mutations. Journal of the National Cancer Institute Cancer Spectrum, 2 (4), 1-13. (doi:10.1093/jncics/pky078).

Record type: Article

Abstract

Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

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181119 IBCCS-KConFab-BCFR_JNCIS_accepted - Accepted Manuscript
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Accepted/In Press date: 8 December 2018
e-pub ahead of print date: 8 March 2019

Identifiers

Local EPrints ID: 427111
URI: http://eprints.soton.ac.uk/id/eprint/427111
PURE UUID: 91f2d2aa-580f-4147-9dc5-7bfdcb46771c
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 03 Jan 2019 10:27
Last modified: 13 Dec 2021 02:35

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Contributors

Author: Mary Beth Terry
Author: Yuyan Liao
Author: Karin Kast
Author: Diana Eccles ORCID iD
Corporate Author: et al.
Corporate Author: EMBRACE
Corporate Author: GENEPSO
Corporate Author: BCFR
Corporate Author: HEBON
Corporate Author: kConFab
Corporate Author: IBCCS

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