Sharpe C R
Department of Epidemiology and Biostatistics, McGill University, Montreal, Que.
CMAJ. 1998 Jul 14;159(1):55-9.
In this article the author proposes that the multicentricity of breast cancer might be explained by a developmental hypothesis. Genetic alterations ("hits") occurring in epithelial stem cells during the development of the breast may be transmitted to populations of daughter cells during growth. As a result, areas of the breast may be predisposed to malignant transformation with the occurrence of further genetic hits. Areas with the same predisposition should be anatomically connected, and earlier hits during breast development should result in larger areas of predisposition. The multicentricity of breast cancer would be explained if multiple lesions--monoclonal for the predisposing genetic hit and polyclonal for subsequent hits--developed within a predisposed area. Multiple lesions arising from the spread of disease by extension would be expected to share many genetic hits. The author discusses the implications that further evidence supporting the developmental hypothesis would have for the prevention and treatment of breast cancer.
在本文中，作者提出乳腺癌的多中心性或许可以用一种发育假说加以解释。在乳腺发育过程中，上皮干细胞中发生的基因改变（“打击”）可能会在生长过程中传递给子代细胞群体。因此，乳腺的某些区域可能因进一步的基因打击而易于发生恶性转化。具有相同易感性的区域在解剖学上应是相连的，并且乳腺发育过程中较早发生的打击应会导致更大的易感性区域。如果在一个易感区域内出现多个病灶——对于引发易感性的基因打击是单克隆的，而对于后续打击是多克隆的，那么乳腺癌的多中心性就可以得到解释。因疾病蔓延扩展而产生的多个病灶预计会有许多共同的基因打击。作者讨论了支持该发育假说的进一步证据对乳腺癌预防和治疗的意义。
