The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
Authors
Publication Date
2018-12Journal Title
JNCI Cancer Spectrum
ISSN
2515-5091
Publisher
Oxford University Press (OUP)
Volume
2
Issue
4
Number
pky078
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Antoniou, A. (2018). The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations. JNCI Cancer Spectrum, 2 (4. pky078) https://doi.org/10.1093/jncics/pky078
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 a 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 (5,707 BRCA1 and 3,525 BRCA2 mutation carriers) and a prospective cohort (2,276 BRCA1 and 1,610 BRCA2 mutation carriers), separately for each cohort and in 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%CI=0.83-1.18). Relative to being uniparous, increased number of FTPs was associated with decreased BC risk (HRc=0.79, 95%CI=0.69-0.91; HRc=0.70, 95%CI=0.59-0.82; HRc=0.50, 95%CI=0.40-0.63, for 2, 3, and ≥4 FTPs, respectively, ptrend<0.0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort ptrend=0.0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective cohort (HRp=1.69, 95%CI=1.09-2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc=1.33, 95%CI=1.05-1.69) and there was no apparent decrease in risk associated with multiparity except for ≥4 FTPs (HRc=0.72, 95%CI=0.54-0.98).
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.
Sponsorship
Cancer Research UK (23382)
Cancer Research UK (20861)
Cancer Research UK (CRUK-A16563)
Cancer Research UK (CRUK-A17523)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1093/jncics/pky078
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288203
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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