CONCLUSIONS, INTERPRETATIONS, AND RECOMMENDATIONS FOR FURTHER RESEARCH

Oral contraceptives, as they have been used to date, have caused little or no overall increase in the risk of breast cancer in women in developed countries. Risks in women of all ages combined have not been appreciably enhanced by more than a decade of exposure or after a potential latent period of up to two decades.

Limited information from developing countries, where rates of breast cancer are much lower than in the developed countries where most studies of oral contraceptives and breast cancer have been conducted, suggests that oral contraceptive use may moderately enhance risk in women in low-risk populations. A possible mechanism for this increase is the stimulation of proliferative activity in the stem cells of the lobular epithelium. Such stimulation may not occur to a measurable extent in high-risk populations of women, whose lobular epithelia may already be maximally stimulated by other (unknown) factors that put these women at high risk. Further studies in low-risk populations are warranted.

Oral contraceptives do not appear to have a differential impact on risk in women with and without such risk factors for breast cancer as high socioeconomic status, nulliparity, low parity, a late first fullterm pregnancy (or live birth), or a family history of breast cancer. Compared to risks of breast cancer among countries, which may differ by a factor of 10, the risks in women with and without each of these risk factors differ by a factor of only about 2 or 3. The potential for the lobular epithelium of the breast of women without these risk factors to be further stimulated by oral contraceptives, compared with this potential in women with these factors, may thus be smaller than the differential potential for lobular stimulation in women in low-and high-risk populations. (It may also be too small to measure by epidemiological means.) Further study of the influence of oral contraceptives in women with and without the generally recognized risk factors for breast cancer should not receive high priority.

Limited information suggests that oral contraceptives (whether used before or after a benign lesion) may enhance the risk of breast cancer in young women with a prior history of benign breast disease but not in older women with such a history. Because the benign lesions in younger women are more likely than the benign lesions in older women to be fibroadenomas, further study of this issue should include young women in particular. It should also include a slide review to characterize the prior benign lesion histologically. In women of all ages combined, the use of oral contraceptives after benign lesions has not



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