Osborne M P, Rosen P P, Lesser M L, Schwartz M K, Menendez-Botet C J, Fishman J H, Kinne D W, Beattie E J
Cancer. 1983 Jun 1;51(11):2134-8. doi: 10.1002/1097-0142(19830601)51:11<2134::aid-cncr2820511130>3.0.co;2-f.
Eight-hundred and thirteen patients were prospectively studied to examine the influence of family history and the prior use of exogenous hormones as covariables in the subsequent expression of estrogen receptor protein (ERP) in the primary tumor of patients with breast cancer. Cases were divided by menstrual status; there were 385 pre- and perimenopausal and 428 postmenopausal patients. The influence of prior exposure to estrogen replacement therapy (ERT) in postmenopausal patients or oral contraceptives (OC) in pre- and perimenopausal patients on tumor ERP was analyzed controlling for family history: none, first degree (1 degree, mother or sister), second degree (2 degrees, grandmother or aunt), or both 1 degree and 2 degrees relatives. The results showed no influence of the prior use of ERT in postmenopausal women on subsequent tumor ERP. Among pre- and perimenopausal women, those with a family history of breast cancer in only a 1 degree relative, showed a borderline significant association between prior OC usage and subsequent tumor ERP. The use of OC was consistently associated with ERP negative tumors (9/9) whereas of 29 patients who had no prior OC exposure 17 had ERP negative tumors (P = 0.04, Fisher's Exact Test). Analysis of the prior exposure to OC, verified with the primary care physician or pharmacist, showed that these patients first used OC at the mean age of 32.2 years, had used OC for a mean duration of 41.9 months and stopped OC use a mean of 79.5 months before being diagnosed as having breast cancer. These results suggest that in a subset of patients with breast cancer, and a first degree relative only who had breast cancer, prior exposure to OC may influence the subsequent ERP status of the tumor. This is not due to exogenous estrogen saturation of receptors as there was a long latent period between exposure and diagnosis. Alternative hypotheses as to the mechanism of selection of subsequent tumor ERP may be either inhibition of ERP positive preneoplastic or tumor cell clones early in the evolution of the tumor or early selection of a tumor capable of endogenous estrogen synthesis with receptor saturation.
对813例患者进行了前瞻性研究，以检验家族史和外源性激素的既往使用作为协变量对乳腺癌患者原发肿瘤中雌激素受体蛋白（ERP）后续表达的影响。病例按月经状态分组；有385例绝经前和围绝经期患者以及428例绝经后患者。分析了绝经后患者既往接受雌激素替代疗法（ERT）或绝经前和围绝经期患者口服避孕药（OC）对肿瘤ERP的影响，并控制家族史：无、一级（1度，母亲或姐妹）、二级（2度，祖母或姑姑）或一级和二级亲属均有。结果显示，绝经后女性既往使用ERT对后续肿瘤ERP无影响。在绝经前和围绝经期女性中，只有一级亲属有乳腺癌家族史的女性，既往OC使用与后续肿瘤ERP之间存在边缘显著关联。OC的使用始终与ERP阴性肿瘤相关（9/9），而在29例既往未接触OC的患者中，17例有ERP阴性肿瘤（P = 0.04, Fisher精确检验）。经初级保健医生或药剂师核实的既往OC接触分析表明，这些患者首次使用OC的平均年龄为32.2岁，使用OC的平均持续时间为41.9个月，在被诊断为乳腺癌前平均79.5个月停止使用OC。这些结果表明，在一部分乳腺癌患者中，且只有一级亲属患有乳腺癌，既往接触OC可能会影响肿瘤的后续ERP状态。这并非由于受体的外源性雌激素饱和，因为接触与诊断之间有很长的潜伏期。关于后续肿瘤ERP选择机制的其他假设可能是在肿瘤演变早期抑制ERP阳性的肿瘤前或肿瘤细胞克隆，或者早期选择能够进行内源性雌激素合成且受体饱和的肿瘤。
