Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Antonis C Antoniou¹ , Andrew Shenton² , Eamonn R Maher⁴ , Emma Watson² , Emma Woodward⁴ , Fiona Lalloo³ , Douglas F Easton¹ and D Gareth Evans³

¹CR-UK Genetic Epidemiology Unit, Strangeways Research Laboratory, Department of Public Health and Primary Care, Worts Causeway, University of Cambridge, Cambridge, CB1 8RN, UK

²Department of Clinical Genetics (SM2), St Mary's Hospital, Hathersage Road, Manchester, M13 0JH, UK

³Academic Unit of Medical Genetics and Regional Genetics Service, St Mary's Hospital, Manchester M13 0JH, UK

⁴Division of Medical Genetics, University of Birmingham School of Medicine, Birmingham, B15 2TT, UK

author email corresponding author email

Breast Cancer Research 2006, 8:R72doi:10.1186/bcr1630


Published:	22 December 2006

Abstract

Introduction

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.

Conclusion

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.