An adaptation of the double antibody radioimmunoassay for insulin originally presented by Morgan and Lazarow is described. These studies have confirmed the presence of an inhibitor in serum and plasma (heparin) which delays the rate at which the insulin-insulin antibody complex is rendered insoluble by rabbit serum containing antibodies to guinea pig globulin. Serum dilution reduces the effect of the inhibitor but increases dilutional error. Heparin similarly reduces the effect of the inhibitor, but excess heparin produces falsely low values for immunoreactive insulin (IRI). Data are presented for serum which show that if sufficient time (72 hrs.) is allowed to elapse after the addition of the precipitating antibody (rabbit, anti-guinea pig globulin, serum), the precipitating system reaches equilibrium. Employing this modification, additional data are presented, showing excellent recovery of human insulin added to serum, good duplication of respective serum IRI values in repeat assays, and constancy of fasting serum IRI in any one individual on repeated sampling. Normal adults exhibit fasting values of serum IRI from 1 to 20 μU./ml. with a mean of 8.4 μU./ml., and after rapid intravenous glucose, serum IRI usually reaches maximum levels in one to two minutes.

Since 1976, data were collected to evaluate risk factors for breast cancer in a hospital-based case-control study of 1185 women with breast cancer and 3227 controls. The risk of breast cancer increased with increasing age at first birth; this effect was not accounted for by parity. An early age at first birth appeared to reduce the risk relative to no pregnancy, whereas a late age at first birth was associated with a higher risk than not having a full-term pregnancy. High parity was associated with a reduction in the risk that was independent of that of age at first birth: for parity greater than or equal to 5, compared with parity 1-2, the relative risk estimate was 0.7 (95% confidence interval, 0.5-1.0). Late age at menarche was associated with a lower risk among premenopausal women but not among postmenopausal women. The relative risk decreased with increasing obesity among premenopausal women. Among postmenopausal women, the risk was higher among those who were obese, but there was no evidence of a trend with increasing body mass index. Risk did not vary materially according to history of abortion when gravidity was controlled. Risk was lower among postmenopausal women than among premenopausal women of the same age and increased with increasing age at menopause; bilateral oophorectomy reduced the risk more than hysterectomy alone. A positive history of benign breast disease, a positive family history of breast cancer, Jewish religion, and 12 or more years of education were each independently associated with an increased risk of breast cancer.

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