Development of the Human Mammary Gland

It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.

This study examines cell turnover within the lobules of the "resting" human breast and correlates it to the stage of the menstrual cycle. The results are based on the morphological identification of both cell multiplication (mitosis) and cell deletion (apoptosis). It is found that these events undergo significant cyclical changes during the menstrual cycle, with raised levels towards the end of the cycle and during menses. However, in relation to a 28-day menstrual cycle, the position of the mitotic and apoptotic peaks, at Days 25 and 28 respectively, are significantly different. The high values are associated with an increase in the number of lobules showing a slight response rather than a large reaction within a few lobules. It appears that the "resting" breast tissue shows a general, rather than a focal reaction to a given hormonal environment. The possible role of oestrogen and progesterone as effectors of these changes is discussed. Our results show that the menstrual cycle influences cell turnover, though different factors may be affecting mitosis and apoptosis.

DNA synthesis in normal breast epithelium from premenopausal women was assessed by use of autoradiography. In parous women the labeling indexes decreased during the follicular phase of the menstrual cycle and increased to a significantly higher level during the luteal phase.