Parental age at delivery and incidence of breast cancer: A prospective cohort study

Background: Studies on parental age at delivery in relation to breast cancer risk have had mixed results, but prospective data are limited. No study has explored the associations with subtypes of breast cancer defined by hormonal receptor status. Methods: 109,773 women in the Nurses' Health Study were followed from 1976 to 2002. We used Cox proportional hazards model to examine the association between parental age at delivery and daughters' risk of breast cancer. Results: 6,827 incident cases of invasive breast cancer occurred in this cohort during 2,581,098 person-years. Adjusting for other early life exposures and family history of breast cancer, the hazard ratio for breast cancer in women born to mothers aged 21-25, 26-30, 31-35, and ≥36 years was, respectively, 1.08 (95% CI: 0.99-1.18), 1.12 (95% CI: 1.03-1.23), 1.17 (95% CI: 1.06-1.29), and 1.12 (95% CI: 1.01-1.25), compared to women born to mothers aged ≤20 years (P for trend = 0.008). Similarly, advanced paternal age was associated with increased incidence of breast cancer (P for trend = 0.03), but the association disappeared when conditioning on maternal age. The positive association between maternal age and incidence of breast cancer was stronger for estrogen receptor-positive and progesterone receptor-positive tumors (P for trend = 0.003) than for tumors with both receptors negative (P for trend = 0.78), and was more consistent among postmenopausal women, women without a family history and women who were first born. Conclusion: Our findings support a modest positive association between maternal age and daughter's risk of breast cancer, possibly mediated by hormonal factors.