The role of reproductive and menstrual factors in cancer of the breast before and after menopause.

The aim of the study was to elucidate the role of reproductive and menstrual factors in the aetiology of breast cancer, overall and by menopausal status. A cooperative case-control study was conducted between 1991 and 1994 in six different Italian areas (including three from the centre and the south). The study included 2569 histologically confirmed incident cases of breast cancer (median age 55 years, range 23-78 years) and 2588 control women (median age 56 years, range 20-79 years) admitted to the same hospitals for a variety of acute conditions unrelated to the hypotheses in study. A trend of increasing risk with increasing age at menopause (odds ratio (OR) for age at menopause > or = 53 versus < 45 years = 1.8; 95% confidence interval (CI) = 1.4-2.2). High parity reduced cancer risk (OR for > or = 4 versus 1 birth = 0.7; 95% CI = 0.5-0.9). Overall, nulliparous women showed a 20% lower risk than uniparous ones (OR = 0.8; 95% CI = 0.7-1.0). Late age at first birth (or pregnancy) had an independent adverse effect (OR for first birth at > or = 32 versus < 20 years = 1.7; 95% CI = 1.3-2.1) both before and after menopause. An approximately 2-fold elevation of breast cancer risk was evident up to 10 years after the last birth. No trend in risk was evident for induced abortions (OR = 1.2 for 1 and 1.1 for > or = 2 induced abortions versus 0). Other examined menstrual and reproductive characteristics did not seem important. Multiparity, early age at first birth and early age at menopause were therefore the most important determinants of breast cancer risk. The effects of the timing of births was significantly heterogeneous in pre- and postmenopausal women because of the transient adverse effect of such events, evident only in premenopausal women.