Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast
Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast
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DOI：
10.1210/jc.84.12.4559
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发表时间：
1999-12-01
影响因子：
5.8
通讯作者：
Haslam, SZ
中科院分区：
文献类型：
--
作者：
Hofseth, LJ;Raafat, AM;Haslam, SZ
绝经后激素替代疗法（HRT）与单独雌激素的相对效果。雌激素+孕激素对乳腺细胞增殖和乳腺癌风险的影响存在争议。进行了一项横断面观察性研究，以检查雌激素或雌激素加孕激素醋酸甲羟孕酮的 HRT 对绝经后妇女乳腺组织的增殖作用。使用抗增殖细胞核抗原（抗 PCNA）和 Ki67 抗体对 86 名绝经后妇女的良性乳腺活检进行分析，以测量细胞增殖的相对水平。还测定了上皮密度以及雌激素和孕激素受体状态。这些女性被分为以下两种类型：1）单独使用雌激素（E）； 2）雌激素；醋酸甲羟孕酮(E+P)；或 3) 无激素替代疗法。与未接受HRT相比，接受E+P或单独E治疗的女性乳腺上皮细胞PCNA增殖指数显着升高，且E+P治疗的指数（PCNA和Ki67）显着高于单独E治疗的女性。与未接受 HRT 治疗的绝经后女性相比，接受 E 和 E+P 治疗的乳腺上皮密度明显更高。因此，本研究表明，与单独使用 E 或不使用 HRT 相比，绝经后 HRT 联合 E+P 与更大的乳腺上皮细胞增殖和乳腺上皮细胞密度相关。此外，通过 E+P，乳腺增殖局限于乳腺的终末导管小叶单位，这是大多数乳腺癌的发生部位。需要进一步的研究来评估孕激素的促有丝分裂活性与乳腺癌风险之间可能的关联。
The relative effects of postmenopausal hormone replacement therapy (HRT) with estrogen alone us. estrogen+progestin on breast cell proliferation and on breast cancer risk are controversial. A cross-sectional observational study was carried out to examine the proliferative effects of HRT with estrogen or estrogen plus the progestin, medroxyprogesterone acetate, in breast tissue of postmenopausal women. Benign breast biopsies from 86 postmenopausal women were analyzed with antiproliferating cell nuclear antigen (anti-PCNA) and Ki67 antibodies to measure relative levels of cell proliferation. Epithelial density and estrogen and progesterone receptor status were also determined. The women were categorized either as users of: 1) estrogen (E) alone; 2) estrogen; medroxyprogesterone acetate (E+P); or 3) no HRT. Compared with no HRT, the breast epithelium of women who had received either E+P or E alone had significantly higher PCNA proliferation indices,;and treatment with E+P had a significantly higher index (PCNA and Ki67) than treatment with E alone. Breast epithelial density was significantly greater in postmenopausal women treated with E and E+P, compared with no HRT. Thus, the present study shows that postmenopausal HRT with E+P was associated with greater breast epithelial cell proliferation and breast epithelial cell density than E alone or no HRT. Furthermore with E+P, breast proliferation was localized to the terminal duct-lobular unit of the:breast, which is the site of development of most breast cancers. Further studies are needed to assess the possible association between the mitogenic activity of progestins and breast cancer risk.