Colditz G A, Frazier A L
Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):567-71.
We have recently published a mathematical model of the etiology of breast cancer based on the data from the Nurses Health Study that extends the Pike model of breast cancer (see Appendix). The most salient feature of the model is that it identifies the years before the first birth of a child as the most crucial in establishing future risk of breast cancer. The extended model includes several additional details of reproductive risk factors, allowing us to quantify the relative importance of each of the reproductive risk factors and to estimate the effect of changes in key determinants of breast cancer. In this review, we present the evidence from both animal studies and epidemiological research that corroborate the critical importance of the exposures that occur before first birth. We argue that research and preventive interventions should now focus on youth. Population-wide prevention strategies are necessary because the inherited genetic risk for breast cancer accounts for no more than 10-15% of all breast cancer cases, leaving 85% of cases diagnosed among women who are not in this high-risk subgroup of the population. An example of a population-based intervention would be the promotion of increased physical activity among young girls that could result in the delay of menarche. An example of additional research that focuses on the importance of early life exposures would be an analysis of the relation between diet and other lifestyle factors during adolescence and the subsequent risk of breast cancer and studies of precursor lesions (atypical hyperplasia). Shifting the focus of breast cancer prevention to this age group is urgently needed.
我们最近基于护士健康研究的数据发表了一个乳腺癌病因的数学模型，该模型扩展了派克乳腺癌模型（见附录）。该模型最显著的特点是，它将首次生育前的数年确定为确立未来乳腺癌风险最为关键的时期。扩展后的模型纳入了生殖风险因素的几个额外细节，使我们能够量化每个生殖风险因素的相对重要性，并估计乳腺癌关键决定因素变化的影响。在这篇综述中，我们展示了来自动物研究和流行病学研究的证据，这些证据证实了首次生育前暴露的至关重要性。我们认为，现在研究和预防干预应聚焦于青少年。全人群预防策略是必要的，因为乳腺癌的遗传风险在所有乳腺癌病例中所占比例不超过10% - 15%，这意味着85%的病例是在不属于该高危亚人群体的女性中被诊断出来的。基于人群的干预措施的一个例子是促进年轻女孩增加体育活动，这可能会导致初潮延迟。专注于早期生活暴露重要性的额外研究的一个例子是分析青春期饮食和其他生活方式因素与随后乳腺癌风险之间的关系，以及对癌前病变（非典型增生）的研究。迫切需要将乳腺癌预防的重点转移到这个年龄组。
