Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers.
BACKGROUND
Increasing parity and age at first full-term pregnancy are established risk factors for breast cancer in the general population. However, their effects among BRCA1 and BRCA2 mutation carriers is still under debate. We used retrospective data on BRCA1 and BRCA2 mutation carriers from the UK to assess the effects of parity-related variables on breast cancer risk.


METHODS
The data set included 457 mutation carriers who developed breast cancer (cases) and 332 healthy mutation carriers (controls), ascertained through families seen in genetic clinics. Hazard ratios were estimated by using a weighted cohort approach.


RESULTS
Parous BRCA1 and BRCA2 mutation carriers were at a significantly lower risk of developing breast cancer (hazard ratio 0.54, 95% confidence interval 0.37 to 0.81; p = 0.002). The protective effect was observed only among carriers who were older than 40 years. Increasing age at first live birth was associated with an increased breast cancer risk among BRCA2 mutation carriers (p trend = 0.002) but not BRCA1 carriers. However, the analysis by age at first live birth was based on small numbers.


CONCLUSIONS
The results suggest that the relative risks of breast cancer associated with parity among BRCA1 and BRCA2 mutation carriers may be similar to those in the general population and that reproductive history may be used to improve risk prediction in carriers.
Antoniou
Antonis C
AC
CR-UK Genetic Epidemiology Unit, Strangeways Research Laboratory, Department of Public Health and Primary Care, Worts Causeway, University of Cambridge, Cambridge, CB1 8RN, UK. antonis@srl.cam.ac.uk
Shenton
Andrew
A
Maher
Eamonn R
ER
Watson
Emma
E
Woodward
Emma
E
Lalloo
Fiona
F
Easton
Douglas F
DF
Evans
D Gareth
DG
D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010298:Parity; D011247:Pregnancy; D012189:Retrospective Studies; D012306:Risk