Breast Development and Physiology

Microscopy, Morphology, and the Menstrual Cycle
Histologic changes in the normal breast have been identified in relation to the endocrine variations of the menstrual cycle.48 Normal menstrual cycle–dependent histologic changes in both stroma and epithelium have been observed.

Cyclic changes in the sex steroid hormone levels during the menstrual cycle profoundly influence breast morphology. Under the influence of follicle-stimulating hormone and luteinizing hormone during the follicular phase of the menstrual cycle, increasing levels of estrogen secreted by the ovarian graafian follicles stimulate breast epithelial proliferation. During this proliferative phase, the epithelium exhibits sprouting, with increased cellular mitoses, RNA synthesis, increased nuclear density, enlargement of the nucleolus, and changes in other intercellular organelles. In particular, the Golgi apparatus, ribosomes, and mitochondria increase in size or number. During the follicular phase, at the time of maximal estrogen synthesis and secretion in midcycle, ovulation occurs. A second peak occurs in the midluteal phase, when luteal progesterone synthesis is maximal. Similarly, progestogens induce changes in the mammary epithelium during the luteal phase of the ovulatory cycles. Mammary ducts dilate, and the alveolar epithelial cells differentiate into secretory cells, with a partly monolayer arrangement. The combination of these sex steroid hormones and other hormones results in the formation of lipid droplets in the alveolar cells and some intraluminal secretion.

The changes in breast epithelium in response to hormones are mediated through either intracellular steroid receptors or membrane-bound peptide receptors. The presence of steroid receptors for estrogen and progestogens in the cytosol of normal mammary epithelium has been demonstrated. Through the binding of these hormones to specific receptors, the molecular changes, with their observed morphologic effects, are induced as physiologic changes. Similarly, membrane receptors are present to mediate the actions of prolactin. Increases in endogenous estrogen can also exert a histamine-like effect on the mammary microcirculation, resulting in an increased, maximal blood flow 3 to 4 days before menstruation, with an average increase in breast volume of 15 to 30 cm3. Premenstrual breast fullness is attributable to increasing interlobular edema and enhanced ductular-acinar proliferation under the influence of estrogens and progestogens. With the onset of menstruation, after a rapid decline in the circulating levels of sex steroid hormones, secretory activity of the epithelium egresses.

Postmenstrually, tissue edema is reduced, and regression of the epithelium ceases as a new cycle begins, with concomitant rises in estrogen levels. Minimum breast volume is observed 5 to 7 days after menstruation. The cyclic changes in breast cellular growth rates are related to hormonal variations in the follicular and luteal phases of the menstrual cycle. Measurement of these changes can be made by observation and measurement of a variety of cellular and nuclear parameters: