We examined the physical activity and other life-style characteristics of 16,936 Harvard alumni, aged 35 to 74, for relations to rates of mortality from all causes and for influences on length of life. A total of 1413 alumni died during 12 to 16 years of follow-up (1962 to 1978). Exercise reported as walking, stair climbing, and sports play related inversely to total mortality, primarily to death due to cardiovascular or respiratory causes. Death rates declined steadily as energy expended on such activity increased from less than 500 to 3500 kcal per week, beyond which rates increased slightly. Rates were one quarter to one third lower among alumni expending 2000 or more kcal during exercise per week than among less active men. With or without consideration of hypertension, cigarette smoking, extremes or gains in body weight, or early parental death, alumni mortality rates were significantly lower among the physically active. Relative risks of death for individuals were highest among cigarette smokers and men with hypertension, and attributable risks in the community were highest among smokers and sedentary men. By the age of 80, the amount of additional life attributable to adequate exercise, as compared with sedentariness, was one to more than two years.

Pregnancy has a dual effect on the risk of breast cancer: it transiently increases the risk after childbirth but reduces the risk in later years. In women with two pregnancies, the short-term adverse effect is masked by the long-term protection imparted by the first pregnancy. A plausible biologic interpretation is that pregnancy increases the short-term risk of breast cancer by stimulating the growth of cells that have undergone the early stages of malignant transformation but that it confers long-term protection by inducing the differentiation of normal mammary stem cells that have the potential for neoplastic change.

No abstract

The importance of age at menarche, age at menopause, height, and obesity as risk factors for breast cancer, and the possible interactions among these factors in breast cancer causation were investigated in a data set collected in the late 1960's, in an international multicenter case-control study. Multiple logistic regression procedures were used to model data from 3,993 breast cancer cases and 11,783 controls from 7 study centers representing the range of international variation of breast cancer incidence. Height and obesity (measured through the weight/height2 index) were independent risk factors for breast cancer among post-menopausal but not pre-menopausal women; post-menopausal women taller by 10 cm had a 12% higher risk of breast cancer (95% confidence interval, CI, 3-21%) and post-menopausal women of average height (say 158 cm) had an 11% higher risk of breast cancer (CI 7-16%) when they were heavier by 10 kg (and, therefore, more obese by 4 kg/m2). Age at menarche was a risk factor among both pre-menopausal and post-menopausal women, a delay of 2 years corresponding to a 10% reduction in breast cancer risk (CI 6-15%). Age at menopause was also a breast cancer risk factor, women with menopause at each 5 year age difference having a 17% higher risk of breast cancer (CI 11-22%). There is evidence of an interaction (deviation from the logistic regression-postulated multiplicativity) between obesity and age at menarche, implying that the protective effect of late menarche may not apply to overweight women or that late menarche may become detrimental in obese women. The estimated relative risk coefficients, when applied to average risk factor levels observed among control women, can explain only a small fraction of the difference in breast cancer incidence between Boston and Tokyo.

Because pregnancy toxemia is associated with low levels of estrogens and neonatal jaundice, severe prematurity, and dizygotic twins with high levels of estrogens, our findings suggest that estrogens and other hormonal factors, known to influence breast cancer risk in the adult, may also play a critical role during the intrauterine period.