INFLUENCE OF PUBERTY ON BREAST TOPOGRAPHY AND NEOPLASIA

青春期对乳房形态和肿瘤的影响

• 批准号: 3192799
• 负责人: JOSE RUSSO
• 金额: $ 20.01万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3192799
• 关键词: adolescence (12-20); age at pregnancy; autoradiography; breast neoplasm /cancer diagnosis; breast neoplasms; cell differentiation; female; growth /development; histogenesis; histology; human pregnant subject; human puberty; human tissue; mammary disorder; mammary epithelium; mammary gland; menstrual cycle; microscopy; middle childhood (6-11); morphology; neoplastic growth; neoplastic transformation; pathologic process; pregnancy; preneoplastic state; reproductive development; statistics /biometry; young adult human (21-34)

The breast develops an array of benign and malignant lesions which become manifest at maturity. These lesions do not arise in a random fashion but they develop in certain specific areas of the breast. From 40-50% of infiltrating ductal carcinomas, the most common breast malignancy, as well as benign lesions such as adenomas and fibrocystic disease, develop preferentially in the upper external quadrant of the breast. There is as yet no explanation for the tendency of these lesions to cluster in such specific topographic area, however, it is postulated that the susceptibility of the upper external quadrant to develop a higher number of neoplasms is modulated by variations in local developmental patterns and differentiation. There is evidence that supports this hypothesis, such as: 1) the breast of young, post-pubertal females possesses a higher number of undifferentiated structures in the upper external than in the other quadrants of the organ; 2) malignant lesions develop in undifferentiated terminal ductal structures; and 3) the presence of undifferentiated structures in the mammary gland associates with the expression of phenotypic changes of cell transformation after in vitro treatment of epithelial cells with chemical carcinogens. Furthermore, experimental data demonstrate that chemically-induced rat mammary cancer occurs when the carcinogen selectively affects the undifferentiated terminal end buds that are more frequently present in the distal portions of thoracic mammary glands of virgin animals. These studies showed that carcinogenic initiation is modulated by gland topography, degree of glandular development and cell kinetic characteristics of the mammary epithelium, suggesting that the pattern of glandular development plays an important role in the breast's lifetime risk of developing neoplasms. The thrust of this proposal is to study in a systematic manner the developmental pattern of the breast from prepuberty to the early adult years, to assess breast development and differentiation in the various topographic areas of the organ, to determine whether variations in cell kinetics are a function of topographic differences in gland development, how pregnancy modifies the pattern of breast development and lastly, whether the development of malignant lesions in the various quadrants of the breast correlates with the number of undifferentiated structures present in those given areas. This knowledge will lay the basis for understanding the role played by gland development and differentiation on the susceptibility of the human breast to malignant transformation.

乳房会出现一系列良性和恶性病变，这些病变会变成 成熟时表现出来。这些病变并不是随机出现的，而是 它们在乳房的某些特定区域发育。 40-50% 浸润性导管癌，也是最常见的乳腺恶性肿瘤 随着腺瘤和纤维囊肿等良性病变的发展 优先在乳房的外上象限。有如 但对于这些病变聚集成这样的趋势还没有解释 然而，假设特定地形区域 外上象限对发展更多数量的敏感性 肿瘤是通过局部发育模式的变化来调节的 差异化。有证据支持这一假设，例如： 1）年轻、青春期后女性的乳房含有较多的 上部外部的未分化结构高于其他部分 器官的象限； 2）未分化的恶性病变 终端导管结构； 3）未分化的存在 乳腺结构与表达相关 体外处理后细胞转化的表型变化 上皮细胞含有化学致癌物质。此外，实验数据 证明当化学物质诱发大鼠乳腺癌时，就会发生 致癌物选择性地影响未分化的末端芽， 更常见于胸乳的远端部分 处女动物的腺体。这些研究表明致癌起始 受腺体地形、腺体发育程度和细胞的调节 乳腺上皮的动力学特征，表明 腺体的发育模式对乳房的发育起着重要作用 终生患肿瘤的风险。该提案的主旨是 系统地研究乳房的发育模式 青春期前到成年早期，评估乳房发育和 器官不同地形区域的分化，以确定 细胞动力学的变化是否是地形的函数 腺体发育的差异，怀孕如何改变腺体发育的模式 乳房发育情况，最后是否发展为恶性病变 乳房各个象限的数量与 这些特定区域中存在未分化的结构。 这些知识 将为理解腺体发育所起的作用奠定基础 人体乳腺恶性肿瘤易感性及分化 转变。