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Molecular Mechanism for Breast Cancer Incidence in the Women's Health Initiative
Cancer Prevention Research ( IF 2.9 ) Pub Date : 2020-07-15 , DOI: 10.1158/1940-6207.capr-20-0082
V Craig Jordan 1
Affiliation  

The Women's Health Initiative (WHI) was designed to evaluate the benefits of hormone replacement therapy. The primary goal was to establish the value of synthetic progestin and estrogen or estrogen alone to reduce the risk of coronary heart disease (CHD). The estrogen/synthetic progestin trial was stopped at 5.2 years and the estrogen trial was stopped after 6.8 years. Although the estrogen/synthetic progestin trial was stopped for the anticipated rise in the risk of breast cancer, the estrogen trial was stopped for elevation of strokes. Women taking estrogen/synthetic progestin or estrogen alone had no benefit from a reduction in CHD. Paradoxically, there was a decrease in breast cancer incidence in the estrogen trial. The decrease in breast cancer was sustained. The elevation of breast cancer in the estrogen/synthetic progestin trial was also sustained a decade after stopping treatment. Evidence is presented to explain the paradoxical sustained decrease in breast cancer with estrogen and the mechanism for the reversal of breast cancer incidence and mortality with the mixed synthetic progestin/glucocorticoid actions of the synthetic progestin used with estrogen in women with an intact uterus. The fact that the WHI study had an estrogen deprivation gap of at least 5 years, introduced an experimental biological dimension not observed in medical practice using progestin/estrogen hormone replacement. The evidence presented confirms the known human cancer biology of estrogen action.

中文翻译:

妇女健康倡议中乳腺癌发病的分子机制

妇女健康倡议 (WHI) 旨在评估激素替代疗法的益处。主要目标是确定合成孕激素和雌激素或单独使用雌激素对降低冠心病 (CHD) 风险的价值。雌激素/合成孕激素试验在 5.2 年后停止,雌激素试验在 6.8 年后停止。尽管雌激素/合成孕激素试验因预期患乳腺癌的风险增加而停止,但雌激素试验因卒中增加而停止。单独服用雌激素/合成孕激素或雌激素的女性并没有从冠心病的减少中获益。矛盾的是,雌激素试验中乳腺癌的发病率有所下降。乳腺癌的减少是持续的。雌激素/合成孕激素试验中乳腺癌的升高在停止治疗后也持续了十年。提供了证据来解释雌激素引起的乳腺癌发病率持续下降的矛盾,以及在具有完整子宫的女性中使用合成孕激素与雌激素的混合合成孕激素/糖皮质激素作用逆转乳腺癌发病率和死亡率的机制。WHI 研究的雌激素剥夺间隔至少为 5 年,这一事实引入了在使用孕激素/雌激素激素替代的医疗实践中未观察到的实验生物学维度。所提供的证据证实了雌激素作用的已知人类癌症生物学。提供了证据来解释雌激素引起的乳腺癌发病率持续下降的矛盾,以及在具有完整子宫的女性中使用合成孕激素与雌激素的混合合成孕激素/糖皮质激素作用逆转乳腺癌发病率和死亡率的机制。WHI 研究的雌激素剥夺间隔至少为 5 年,这一事实引入了在使用孕激素/雌激素激素替代的医疗实践中未观察到的实验生物学维度。所提供的证据证实了雌激素作用的已知人类癌症生物学。提供了证据来解释雌激素引起的乳腺癌发病率持续下降的矛盾,以及在具有完整子宫的女性中使用合成孕激素与雌激素的混合合成孕激素/糖皮质激素作用逆转乳腺癌发病率和死亡率的机制。WHI 研究的雌激素剥夺间隔至少为 5 年,这一事实引入了在使用孕激素/雌激素激素替代的医疗实践中未观察到的实验生物学维度。所提供的证据证实了雌激素作用的已知人类癌症生物学。WHI 研究的雌激素剥夺间隔至少为 5 年,这一事实引入了在使用孕激素/雌激素激素替代的医疗实践中未观察到的实验生物学维度。所提供的证据证实了雌激素作用的已知人类癌症生物学。WHI 研究的雌激素剥夺间隔至少为 5 年,这一事实引入了在使用孕激素/雌激素激素替代的医疗实践中未观察到的实验生物学维度。所提供的证据证实了雌激素作用的已知人类癌症生物学。
更新日期:2020-07-15
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