The fundamental form of maternal support to the newborn of mammals is provided as liquid nourishment (milk).
Functional anatomy. Mammary glands are designed for synthesis, secretion, and storage of milk. While the number of mammary units may differ between species (from two in the human to 25 in the opossum), functional components are basically analogous. Each mammary gland is composed of lobules subdivided by fat and stroma. Each lobule contains an independent network of clustered alveoli (Figure 5-39). The alveolus is a sac-like structure surrounded by glandular epithelia (alveolar cells) and specialized contractile elements (myoepithelium) (Figures 5-40 and 5-41). Alveolar cells synthesize milk. Myoepithelial cells are responsible for secretion of milk (let-down or ejection); they squeeze the milk into the cavity of the alveolus. In rats, rabbits, and pigs the majority of milk is stored within the alveoli. In humans and ruminants the milk ducts transport the displaced secretory material (under pressure) to larger collecting units - sinuses and udder cisterns, respectively.
Neuroendocrinology of lactation. Ovarian steroid hormones initiate mammary development at puberty. During gestation the mammary gland undergoes further maturational changes in preparation for production of milk (lactogenesis). The main effects of estrogens and progesterone are to stimulate alveolar and ductal proliferation, respectively. Estrogens also cause deposition of adipose tissue within the mammary gland. Exposure of the fetus to hormones of pregnancy can result in temporary breast enlargement and some secretion of fluid ("witch's milk").
Secretion of prolactin increases after parturition. Prolactin is involved in initiation of lactation; it elicits synthesis of lactose, casein, and triglycerides. Growth hormone (to include recombinant forms) significantly increases yield of milk in ruminants; it appears to work outside the mammary gland, possibly via production of hepatic somatomedins.
Additional hormones (placental lactogen, insulin, glucocorticoids, thyroid hormones) contribute to functional differentiation of the mammary gland and lactogenesis. Thus, lactation is maintained by the combined action of hormones (released in response to episodes of suckling). The mammary gland gradually becomes refractory to hormonal stimulation following the postpartum peak in lactation. Lactogenesis is inhibited by progesterone and long-acting estrogens.
Oxytocin causes milk let-down in reaction to a suckling or mechanical milking stimulus (which also potentiates prolactin release); the neurosecretory pathway of this response is outlined in Figure 5-42. Release of oxytocin also can occur without a suckling stimulus (ie., as a conditioned reflex). Dairy cows who have become accustomed to activity in the barn preceding the time of actual milking will release their milk spontaneously. Likewise, human mothers will often let down their milk upon hearing (or even anticipate) the cry of their infant.
Colostrum. Colostrum is the milk produced at the onset of lactation. Colostrum contains maternal antibodies - providing the newborn with a degree of passive immunity. It is especially beneficial that the young of species with a significant placental barrier (eg., farm animals) consume colostrum (antibodies are not efficiently transferred in utero); this form of protection is conveyed to the fetus before birth in animals that develop a close fetal-maternal alliance.
Cancer. Breast cancer is the most common malignancy in women. Most aberrant growths of the breast are not malignant (eg., dysplasia [fibrocystic disease] and fibroadenoma). Some form of benign breast disease, which usually does not require treatment, affects nearly one-half of women more than 30 years of age. Approximately 120,000 new incidents of carcinoma are diagnosed in the United States every year; about 40,000 cases prove lethal. The majority of clinical manifestations occur in women in their fifties. A variety of risk factors predispose women to breast cancer (Table 5-15). Breast cancer in men is rare, but almost always fatal.
Early detection of a malignant breast tumor is extremely important in successful management of the disease (ie., prevention of a localized condition from becoming systemic). Self-examination of the breasts should be carried out on a routine basis. Confirmation of a palpated lump as malignant or benign generally requires mammography and a biopsy of tissue for histological examination (Figure 5-43). An elevation in tumor-derived circulatory hCG occurs in some patients.
One-half or more of cancers of the breast are associated with heightened tissue levels of receptors for estrogens. However, possible cause-and-effect relationships between the role of estrogens in initiation of carcinogenesis remain undefined.
Surgical treatment of breast cancer can range from a partial to a radical mastectomy. In a radical mastectomy the entire breast is removed with adjacent axillary lymph nodes and pectoralis muscle. In some cases oophorectomy, adrenalectomy, or hypophysectomy helps in regression of estrogen-receptive breast tumors. Antiestrogen therapy is an alternative to surgery. As with other forms of cancer, less selective approaches to management can be implemented, including irradiation and(or) chemotherapy.