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/jcem.84.12.6194
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发表时间：
1999-12
期刊：
影响因子：
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通讯作者：
L. Hofseth;A. Raafat;J. Osuch;Dorothy Pathak;C. Slomski;S. Haslam
中科院分区：
文献类型：
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作者：
L. Hofseth;A. Raafat;J. Osuch;Dorothy Pathak;C. Slomski;S. Haslam
绝经后激素替代疗法（HRT）单独使用雌激素与雌激素+孕酮对乳腺细胞增殖和乳腺癌风险的相对影响存在争议。本研究采用横断面观察研究方法，观察HRT联合雌激素或雌激素联合孕激素、醋酸甲羟孕酮对绝经后妇女乳腺组织增殖的影响。我们用抗增殖细胞核抗原（抗PCNA）和Ki 67抗体分析了86例绝经后妇女的良性乳腺活检组织，以测量细胞增殖的相对水平。上皮密度和雌激素和孕激素受体状态也进行了测定。这些妇女被分为：1）单独使用雌激素（E）; 2）雌激素+醋酸甲羟孕酮（E+P）;或3）没有HRT。与没有HRT相比，接受E+P或单独E的女性乳腺上皮细胞具有显著更高的PCNA增殖指数，并且E+P治疗具有显著更高的指数（PCNA和Ki 67）比单独E治疗。与未接受HRT的绝经后妇女相比，接受E和E+P治疗的绝经后妇女的乳腺上皮密度显著增加。因此，目前的研究表明，绝经后HRT与E+P与更大的乳腺上皮细胞增殖和乳腺上皮细胞密度比E单独或没有HRT。此外，在E+P中，乳腺增生局限于乳腺的终末导管-小叶单位，这是大多数乳腺癌发生的部位。需要进一步的研究来评估孕激素的促有丝分裂活性和乳腺癌风险之间的可能联系。
The relative effects of postmenopausal hormone replacement therapy (HRT) with estrogen alone vs. 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.