Stoll B A
Oncology Department, St Thomas' Hospital, London, UK.
Int J Obes Relat Metab Disord. 1998 Nov;22(11):1035-40. doi: 10.1038/sj.ijo.0800769.
While most studies show a higher body mass in Western women to be positively associated with an increased breast cancer risk in postmenopausal women, they show a negative association in the case of premenopausal women. A review of case-control and cohort studies suggest that such protection applies mainly to obesity in teenage girls, whereas obesity appearing after the teenage years is more likely to be associated with a higher risk of postmenopausal breast cancer. The mechanisms are uncertain. There is evidence that obesity and the components of the Western diet can independently provoke hyperinsulinaemic insulin resistance at puberty, and in adolescent girls this has been related to evidence of abnormal ovarian steroidogenesis and anovulation. This may decrease promotion of mammary carcinogenesis. If however, obesity continues after the teenage years, the higher concentration of insulin-like growth factor 1 (IGF1) associated with hyperinsulinaemia can interact with oestrogen receptors in mammary epithelium to lead to increased proliferative activity. This review postulates that the observed protective effect of early obesity against premenopausal breast cancer is likely to be replaced by an increased risk of postmenopausal breast cancer if obesity continues after the teenage years. The manifestation of breast cancer is merely postponed to an older age. Recent prospective and case-control studies suggest that increased bioavailability of IGF1 is a marker of increased breast cancer risk in premenopausal women. Nutritional intake in early life may programme later activity in the growth hormone-IGF1 axis and influence the progression of transformed cells in mammary tissue. The question remains whether deliberate weight loss can reverse the effects of weight gain.
虽然大多数研究表明，西方女性较高的体重指数与绝经后女性患乳腺癌风险增加呈正相关，但在绝经前女性中却呈负相关。一项对病例对照研究和队列研究的综述表明，这种保护作用主要适用于少女肥胖，而青少年期之后出现的肥胖更有可能与绝经后乳腺癌风险增加相关。其机制尚不确定。有证据表明，肥胖和西方饮食成分可在青春期独立引发高胰岛素血症性胰岛素抵抗，在青春期女孩中，这与卵巢类固醇生成异常和无排卵的证据有关。这可能会减少对乳腺癌发生的促进作用。然而，如果肥胖在青少年期之后仍持续存在，与高胰岛素血症相关的胰岛素样生长因子1（IGF1）浓度升高可与乳腺上皮中的雌激素受体相互作用，导致增殖活性增加。这篇综述推测，如果肥胖在青少年期之后仍持续存在，那么早期肥胖对绝经前乳腺癌的保护作用可能会被绝经后乳腺癌风险增加所取代。乳腺癌的表现仅仅被推迟到了老年。近期的前瞻性研究和病例对照研究表明，IGF1生物利用度增加是绝经前女性患乳腺癌风险增加的一个标志。早年的营养摄入可能会影响生长激素 - IGF1轴的后期活动，并影响乳腺组织中转化细胞的进展。问题仍然是，刻意减肥是否能逆转体重增加的影响。
