Kuller L H
Department of Epidemiology, GSPH, University of Pittsburgh, PA 15261, USA.
Public Health Rev. 1995;23(2):157-213.
Breast cancer is likely caused by the interaction of exposure to environmental carcinogens at an early age, resulting in initiation of neoplastic transformation and growth factors that determine the likelihood of progression to clinical disease. The environmental carcinogens are numerous (each contributing relatively little to overall risk) and probably interact with genetic "host susceptibility". Most women probably have subclinical breast cancer. The growth of the breast cancer is related to sex-hormone levels at the breast and stimulation of local growth factors. Genetic factors (i.e. host susceptibility including polymorphisms related to the enzymes that affect hormone levels, estrogen/progesterone receptors, and protein synthesis) are probably very important. Reproductive and menstrual patterning during the premenopause, especially related to pregnancy, menstrual cycling and lactation are very important determinants of the risks of breast cancer. More attention needs to be placed on the determinants of menstrual cycling and hormone levels in premenopausal women, especially the relationship of obesity, fat distribution and exercise. The degree of obesity, age at onset of obesity, weight gain (peri- to postmenopausal), and possibly body fat distribution are the major determinants of postmenopausal estrogen levels are key risk factors for postmenopausal breast cancer. Dietary fat, fiber, and perhaps other nutrients, also contribute to blood estrogen levels. Other hormones, especially insulin and insulin-like growth factors, and possibly testosterone and androgens, may also contribute to the increased risk of breast cancer. The reduction of breast cancer incidence and mortality will depend, primarily, on modifications of women's lifestyles which would move them from higher to lower estrogen characteristics.
乳腺癌可能是由于早年接触环境致癌物相互作用所致，从而引发肿瘤转化以及决定进展为临床疾病可能性的生长因子。环境致癌物种类繁多（每种对总体风险的贡献相对较小），且可能与遗传“宿主易感性”相互作用。大多数女性可能患有亚临床乳腺癌。乳腺癌的生长与乳腺处的性激素水平以及局部生长因子的刺激有关。遗传因素（即宿主易感性，包括与影响激素水平的酶、雌激素/孕激素受体及蛋白质合成相关的多态性）可能非常重要。绝经前的生殖和月经模式，尤其是与怀孕、月经周期和哺乳相关的模式，是乳腺癌风险的非常重要的决定因素。需要更多关注绝经前女性月经周期和激素水平的决定因素，尤其是肥胖、脂肪分布与运动之间的关系。肥胖程度、肥胖起始年龄、体重增加（围绝经期到绝经后）以及可能的体脂分布是绝经后雌激素水平的主要决定因素，而绝经后雌激素水平是绝经后乳腺癌关键的风险因素。膳食脂肪、纤维以及或许其他营养素也会影响血液雌激素水平。其他激素，尤其是胰岛素和胰岛素样生长因子，以及可能的睾酮和雄激素，也可能促使乳腺癌风险增加。降低乳腺癌发病率和死亡率将主要取决于改变女性的生活方式，使她们从具有较高雌激素特征转变为较低雌激素特征。
