Stanford J L, Thomas D B
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Epidemiol Rev. 1993;15(1):98-107. doi: 10.1093/oxfordjournals.epirev.a036120.
More research on the effect of exogenous progestins on breast cancer risk is clearly needed. Biologic evidence that progestins may act synergistically with estrogen to enhance proliferation of breast epithelial cells emphasizes the importance of further exploration of this issue, particularly given the increasing prevalence of exposure to contraceptive and noncontraceptive progestins. No specific type or dose of progestin in monophasic combination oral contraceptives has been linked to breast cancer. Based on the few epidemiologic studies of progestin-only oral contraceptives, there also is no evidence that they increase risk of breast cancer. Two studies found that longer-term use of progestin-only pills was associated with a decreased risk of breast cancer. However, given the low prevalence of use of minipills, it is unlikely that this exposure substantially affects the incidence of breast cancer in the population as a whole. Use of the injectable contraceptive DMPA has been positively associated with risk of breast cancer in some subgroups of women, although no significant overall adverse effect has been observed in the two largest studies conducted to date. There is suggestive evidence that use at an early age or prior to a first term birth and recent use may increase risk of breast cancer. It remains unclear, however, whether or not surveillance bias may explain the positive association observed in recent users. Additional research on DMPA and breast cancer incidence is needed, since studies published to date have lacked sufficient power to evaluate risk in relation to long-term use. Future studies of breast cancer in relation to use of other long-acting progestational agents such as Norplant will also be important. There is concern about the relation between breast cancer incidence and use of combined estrogen-progestin replacement therapy, especially extended periods of use. At the present time, only one study (45) has estimated risk according to duration of use, and it remains uncertain whether the reported elevation in risk seen in long-term users of combined therapy is due to enhanced surveillance for breast cancer among exposed women. Further research will be required before any definitive conclusions can be reached about the potential effect of estrogen-progestin replacement regimens on breast cancer incidence. Future studies should attempt to determine the circumstances under which progestins may alter risk of breast cancer and whether such effects vary by duration of use, dosage, type of preparation, concomitant use of estrogens, regimen of exposure, and the timing of progestin use in relation to age and menstrual and reproductive events.(ABSTRACT TRUNCATED AT 400 WORDS)
显然需要对外源孕激素对乳腺癌风险的影响开展更多研究。孕激素可能与雌激素协同作用以促进乳腺上皮细胞增殖的生物学证据凸显了进一步探究此问题的重要性，特别是考虑到接触避孕和非避孕孕激素的情况日益普遍。单相复方口服避孕药中没有特定类型或剂量的孕激素与乳腺癌相关联。基于仅针对含孕激素口服避孕药的少数流行病学研究，也没有证据表明它们会增加乳腺癌风险。两项研究发现，长期使用仅含孕激素的药丸与乳腺癌风险降低有关。然而，鉴于迷你避孕药的使用普及率较低，这种接触不太可能对总体人群中的乳腺癌发病率产生实质性影响。注射用避孕药醋酸甲羟孕酮（DMPA）的使用在某些女性亚组中与乳腺癌风险呈正相关，尽管在迄今为止开展的两项最大规模研究中未观察到显著的总体不良影响。有提示性证据表明，早年或首次足月分娩前使用以及近期使用可能会增加乳腺癌风险。然而，尚不清楚监测偏倚是否可以解释在近期使用者中观察到的正相关关系。由于迄今为止发表的研究缺乏足够的效力来评估与长期使用相关的风险，因此需要对DMPA和乳腺癌发病率开展更多研究。未来关于乳腺癌与使用其他长效孕激素制剂（如皮下埋植剂）之间关系的研究也将很重要。人们对乳腺癌发病率与联合雌激素 - 孕激素替代疗法的使用之间的关系表示担忧，尤其是长期使用。目前，仅有一项研究根据使用时长估计了风险，联合疗法长期使用者中报告的风险升高是否归因于暴露女性中对乳腺癌的加强监测仍不确定。在就雌激素 - 孕激素替代方案对乳腺癌发病率的潜在影响得出任何明确结论之前，还需要进一步研究。未来的研究应尝试确定孕激素可能改变乳腺癌风险的情况，以及这种影响是否因使用时长、剂量、制剂类型、雌激素的同时使用、暴露方案以及孕激素使用与年龄、月经和生殖事件的时间关系而异。（摘要截选至400字）
