The second problem in interpreting recent findings is that in several of the best investigations, such as the U.K. National Study (U.K. National Case-Control Study Group, 1989), the relative risk estimates are close to 1.0. With relative risks of this order, epidemiologists find it difficult to exclude the possible influences of bias, confounding, and chance (Skegg, 1988). With regard to precautions taken to minimize and assess potential sources of bias, the U.K. National Study is the most adequate case-control study so far conducted; nevertheless, some problems remain. For example, selection (or nonresponse) bias is a possibility because only 72 percent of eligible cases could be interviewed (16 percent had died). Examination of general practice case-notes showed that the women with breast cancer who were not interviewed had, on average, significantly less oral contraceptive use than those who were interviewed. Data presented in the paper suggest that the relative risks should probably be scaled down by about 20 percent to allow for this bias, which would bring them even closer to 1.0.

The possibility of modification of the relative risk by confounding factors is always present in studies of this issue. Adjustments are made for known confounding variables but, because the main causes of breast cancer are unknown, unsuspected factors could be associated with both choosing oral contraception and the risk of developing breast cancer.

Cohort studies are free of some, although not all, of the sources of bias that can affect case-control studies, and definitive conclusions may be possible only with the completion of cohort studies containing large numbers of young women—such as the new Nurses' Health Study. The best synthesis of the evidence so far available from case-control and cohort studies is that oral contraceptives do produce a modest increase in the risk of developing breast cancer at a young age (up to about 35 years). This was the provisional conclusion reached by Sir Richard Doll, in summing up a recent conference at which data from most of the major studies were presented (Doll, 1990). Doll concluded that use of oral contraceptives produces no material increase in the risk of developing breast cancer after the age of about 45. With regard to the 35- to 44-year-old age group, he thought that it is “reasonable to postulate that there is some tailing off of the effect” occurring at younger ages.

AN EFFECT IN YOUNG WOMEN

If any adverse effect of oral contraceptives is confined to the risk of breast cancer developing at a young age, the situation is close to



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