Lagiou Pagona, Georgila Christina, Samoli Evangelia, Lagiou Areti, Zourna Pantelina, Minaki Ploumitsa, Vassilarou Dorothy, Papadiamandis Ioannis, Sfikas Constantinos, Kalapothaki Victoria, Sekeris Constantine E, Trichopoulos Dimitrios
Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, and First Department of Surgery, Elena Venizelou Hospital, Athens, Greece.
Int J Cancer. 2009 Jan 15;124(2):440-2. doi: 10.1002/ijc.23899.
Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. In a study in Greece, we determined estrogen alpha and progesterone receptor expression in normal mammary tissue adjacent to the pathological tissue from 267 women with breast cancer and 299 women with benign breast disease. Mouse monoclonal antibodies specific for estrogen receptor alpha and progesterone receptor were applied. The H-index, which incorporates frequency and intensity of staining of the cells, and can range from 0 to 300, was deemed positive when it exceeded 9. Among premenopausal women, there was no evidence for an association with breast cancer risk for expression of either type of receptors. Among postmenopausal women, breast cancer risk was inversely associated with expression of both estrogen alpha (odds ratio (OR)=0.39; p=0.015) and progesterone (OR=0.40; p=0.008) receptors. The hypothesis that overexpression of estrogen receptors alpha or progesterone receptors in normal breast epithelium may increase the risk of breast cancer was not supported by our data. Instead, we found evidence that overexpression of these receptors may be associated with reduced risk for breast cancer in line with the well-known association of expression of these receptors in the malignant tissue and better breast cancer prognosis.
雌激素在乳腺癌的病因学中起着核心作用，观察性研究和随机试验的结果也表明孕激素与之有关。这些激素在乳腺组织中的作用是通过与细胞核中的特定受体蛋白结合来实现的。有人提出，正常乳腺上皮中雌激素受体α的高表达可能会增加患乳腺癌的风险。在希腊进行的一项研究中，我们测定了267例乳腺癌患者和299例乳腺良性疾病患者病理组织旁正常乳腺组织中雌激素α和孕激素受体的表达。应用了对雌激素受体α和孕激素受体具有特异性的小鼠单克隆抗体。H指数综合了细胞染色的频率和强度，范围从0到300，超过9时被认为是阳性。在绝经前女性中，没有证据表明这两种受体的表达与患乳腺癌的风险有关。在绝经后女性中，患乳腺癌的风险与雌激素α（优势比（OR）=0.39；p=0.015）和孕激素（OR=0.40；p=0.008）受体的表达呈负相关。我们的数据不支持正常乳腺上皮中雌激素受体α或孕激素受体的过表达可能增加患乳腺癌风险这一假设。相反，我们发现有证据表明，这些受体的过表达可能与患乳腺癌风险降低有关，这与这些受体在恶性组织中的表达与较好的乳腺癌预后之间的众所周知的关联一致。
