Combined effect of childbearing, menstrual events, and body size on age-specific breast cancer risk.

Pike et al. (Nature 1983;303:767-70) and Moolgavkar et al. (JNCI 1980;65:59-69) proposed quantitative theories for the effect on age-specific breast cancer risk of ages at menarche, first childbirth, and menopause. Here the incidence rate functions predicted by these theories are fit to data for 1,884 women of all ages with breast cancer and 3,432 matched controls admitted to San Francisco Bay area hospitals in 1970-1977. A third function describing age-specific breast cancer risk based on the timing of childbearing and menstrual events is presented, and its fit to the data is compared with that of the functions of Pike et al. and Moolgavkar et al. None of the three fully accounted for the protective effects of early age at first childbirth in premenopausal women or of early age at menopause in parous postmenopausal women. To account for the effects of total parity and body mass (Quetelet) index on risk of breast cancer occurrence, the authors developed a fourth incidence rate function by extending the third. Goodness of fit to the data of the fourth function is demonstrated. Age-specific relative risks of breast cancer according to childbearing, menstrual events, and body size are estimated from the fourth function. The main qualitative findings are that 1) the protective effects of late menarche and of early first full-term pregnancy are greater in premenopausal than in postmenopausal women; 2) first full-term pregnancy initially boosts the level of risk, but incidence rates increase with age more slowly thereafter; 3) among the parous, multiparity is protective both in premenopausal and postmenopausal women, regardless of age at first full-term pregnancy; 4) both nulliparous and lean women are more protected by early menopause than are parous and overweight women; 5) increased body mass index is protective before, but detrimental after, menopause; and 6) postmenopausal incidence rates increase with age more rapidly among overweight than among lean women.