van Leeuwen F E
Department of Epidemiology, Netherlands Cancer Institute, Amsterdam.
Acta Endocrinol (Copenh). 1991;125 Suppl 1:13-26.
This review focuses on epidemiologic studies of the relationship between breast cancer risk and exogenous progestagens, as present in oral contraceptives, injectable contraceptives and hormone replacement therapy. Subsequently, it will be discussed whether the present findings are consistent with one of the hypotheses that have been postulated for the role of hormones in breast cancer pathogenesis. The relationship between oral contraceptives and breast cancer is still controversial. Several studies have found that prolonged oral contraceptives use at young ages is associated with increased risk to develop breast cancer at an early age, i.e. before age 35. None of these studies, however, has been able to attribute the increased risk to specific formulations of oral contraceptives, or to the progestagen content of the preparations. This may be largely due to the fact that there is no good method to calculate progestagen potencies of different formulations. There are no reliable data regarding the effect of progestagen-only oral contraceptives on breast cancer risk. Studies conducted so far included only few women who used these preparations exclusively and for an extended period. Use of injectable contraceptives, mainly depot-medroxy-progesterone acetate, may slightly increase breast cancer, but current findings are inconclusive. There is suggestive evidence that the addition of progestagens to estrogen replacement therapy may increase breast cancer risk over that associated with exposure to estrogens alone. However, the data are not sufficient to warrant any recommendation about changes in clinical practice, and more studies of estrogen-progestagen replacement therapy are needed to settle this issue. It is argued that the "unopposed estrogen" hypothesis for breast cancer is not consistent with the known effects of oral contraceptives and estrogen replacement therapy. The "estrogen plus progestagen" hypothesis seems to be more consistent with current epidemiologic findings. This hypothesis predicts that prolonged exposure to estrogens alone carries a slightly increased breast cancer risk, whereas the combination of estrogens and progestagens increases the risk much more. Future studies will show whether the "estrogen plus progestagen" hypothesis can indeed explain the effects of oral contraceptives and estrogen-progestagen replacement therapy on breast cancer risk.
本综述聚焦于乳腺癌风险与外源性孕激素之间关系的流行病学研究，这些外源性孕激素存在于口服避孕药、注射用避孕药及激素替代疗法中。随后，将讨论目前的研究结果是否与已提出的关于激素在乳腺癌发病机制中作用的假说之一相符。口服避孕药与乳腺癌之间的关系仍存在争议。多项研究发现，年轻时长期使用口服避孕药与早年（即35岁之前）患乳腺癌风险增加有关。然而，这些研究均未能将风险增加归因于特定的口服避孕药配方或制剂中的孕激素含量。这可能主要是因为没有计算不同配方孕激素效力的好方法。关于仅含孕激素的口服避孕药对乳腺癌风险影响的可靠数据并不存在。迄今为止开展的研究仅纳入了少数长期单独使用这些制剂的女性。使用注射用避孕药，主要是醋酸甲羟孕酮长效注射液，可能会略微增加乳腺癌风险，但目前的研究结果尚无定论。有提示性证据表明，在雌激素替代疗法中添加孕激素可能会使乳腺癌风险高于仅暴露于雌激素时的风险。然而，现有数据不足以支持就临床实践的改变提出任何建议，需要更多关于雌激素 - 孕激素替代疗法的研究来解决这一问题。有人认为，乳腺癌的“无对抗雌激素”假说与口服避孕药和雌激素替代疗法的已知作用不符。“雌激素加孕激素”假说似乎与当前的流行病学研究结果更为一致。该假说预测，单独长期暴露于雌激素会使患乳腺癌风险略有增加，而雌激素与孕激素联合使用会使风险增加得更多。未来的研究将表明“雌激素加孕激素”假说是否确实能够解释口服避孕药和雌激素 - 孕激素替代疗法对乳腺癌风险的影响。
