Synthetic progestogens (progestins) have been linked to increased breast cancer risk; however, the role of endogenous progesterone in breast physiology and carcinogenesis is less clearly defined. Mechanistic studies using cell culture, tissue culture, and preclinical models implicate progesterone in breast carcinogenesis. In contrast, limited epidemiologic data generally do not show an association of circulating progesterone levels with risk, and it is unclear whether this reflects methodologic limitations or a truly null relationship. Challenges related to defining the role of progesterone in breast physiology and neoplasia include: complex interactions with estrogens and other hormones (eg, androgens, prolactin, etc.), accounting for timing of blood collections for hormone measurements among cycling women, and limitations of assays to measure progesterone metabolites in blood and progesterone receptor isotypes (PRs) in tissues. Separating the individual effects of estrogens and progesterone is further complicated by the partial dependence of PR transcription on estrogen receptor (ER)α-mediated transcriptional events; indeed, interpreting the integrated interaction of the hormones may be more essential than isolating independent effects. Further, many of the actions of both estrogens and progesterone, particularly in "normal" breast tissues, are driven by paracrine mechanisms in which ligand binding to receptor-positive cells evokes secretion of factors that influence cell division of neighboring receptor-negative cells. Accordingly, blood and tissue levels may differ, and the latter are challenging to measure. Given conflicting data related to the potential role of progesterone in breast cancer etiology and interest in blocking progesterone action to prevent or treat breast cancer, we provide a review of the evidence that links progesterone to breast cancer risk and suggest future directions for filling current gaps in our knowledge.

中文翻译：

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孕酮和乳腺癌。

合成孕激素（孕激素）与乳腺癌风险增加有关。然而，内源性孕激素在乳房生理和癌变中的作用尚不清楚。使用细胞培养，组织培养和临床前模型进行的机理研究表明，孕激素与乳腺癌的发生有关。相比之下，有限的流行病学数据通常未显示循环孕酮水平与风险之间的关联，并且尚不清楚这是否反映了方法学上的局限性或真正的无效关系。定义孕激素在乳房生理和肿瘤形成中的作用涉及的挑战包括：与雌激素和其他激素（例如，雄激素，催乳素等）的复杂相互作用，说明骑自行车的女性进行激素测量的采血时间，测量血液中孕酮代谢物和组织中孕酮受体同种型（PRs）的方法的局限性和局限性。由于PR转录对雌激素受体（ER）α介导的转录事件的部分依赖性，将雌激素和孕酮的单独作用分开更加复杂。实际上，解释激素的整体相互作用可能比分离独立作用更为重要。此外，雌激素和孕激素的许多作用，特别是在“正常”的乳腺组织中，都是由旁分泌机制驱动的，在这种机制中，配体与受体阳性细胞的结合引起了影响邻近受体阴性细胞分裂的因子的分泌。因此，血液和组织的水平可能不同，并且后者的测量具有挑战性。