elongate. The epithelial cells proliferate from stem cells distributed throughout the gland. During the second trimester, differentiation of alveoli from terminal end buds predominates. The alveoli possess two layers of cells, the luminal cells are the prospective secretory cells, while the basal cells are myoepithelial and extend contractile processes in a network around the alveolus. There are low levels of secretion from cells in the ductules and more mature alveoli. During the third trimester, the alveoli mature. The epithelial cells become cuboidal, with an extensive basal endoplasmic reticulum, basally situated nuclei, apical granules and cytoplasmic lipid droplets.
The functional gland architecture is maintained by prolactin, released from the anterior pituitary in response to a suckling stimulus from the infant.
Lactation ceases at the end of the suckling period. Epithelial cells numbers are reduced through apoptosis, the remaining cells become inactive and reduced in size and alveoli and ducts regress back to a resting state. The stromal fibroblasts reconstruct the collagenous interlobular connective tissue and the gland becomes reinvaded with adipose tissue. Though the post lactational breast returns to a resting state, the architecture of the gland and composition of the supporting tissues are not identical to their structures before pregnancy.
1.4.2.4 Menopause
The resting state is maintained in a manner similar to that of the post-pubertal gland, with the potential to re-enter the fully functional state during subsequent pregnancies. The amount of elastic tissue increases, the stroma becomes more fibrous and less cellular and adipose tissue is lost. The levels of circulating ovarian hormones falls, the ductal elements degenerate and dense connective tissue replaces the intralobular loose connective tissue.
1.5 CANCER
Cancer results from a series of genetic alterations that confer a loss of growth control plus the development of invasive, angiogenic, and metastatic capabilities.
The vast majority of breast cancers are carcinomas, the malignant tumours of the epithelia. Based upon histological evaluations, development of the breast cancer has been postulated to be a multi-step process and follows a defined sequence of qualitatively different events, as documented for a number of other malignancies (Russo et al., 1993; Russo et al., 1997).
In the human breast, ductal hyperplasia and atypical ductal hyperplasia represent the initial stages of neoplastic growth and progress gradually to ductal carcinoma in situ, invasive ductal carcinoma and ultimately metastasis, even though normal cells could directly give rise to ductal carcinoma in situ or invasive ductal carcinoma (Fig. 1.20).
Figure 1.20: Stages of Tumour Development
In the human breast, ductal hyperplasia and atypical ductal hyperplasia represent the initial stages of neoplastic growth and progress gradually to ductal carcinoma in situ, invasive ductal carcinoma and ultimately metastasis, even though normal cells could directly give rise to ductal carcinoma in situ or invasive ductal carcinoma. Indicated is the timescale in years.
The goal of any breast cancer treatment is to achieve effective local-regional control of the tumour in order to maximise the chance for cure. There are four main kinds of conventional treatment; surgery (removing the cancer with an operation), radiation therapy (killing the cancer cells with radiation), chemotherapy (killing the cancer cells with drugs) and hormone therapy (stopping the cells from growing with hormone blocking agents). The type of treatment that will work best for the patient depends the stage of their cancer. Primary tumour treatment is relatively successful but it is still difficult to treat metastases.
The development of new treatments for breast cancer during the past decade has been actively progressing. The ability to characterise tumours at the molecular level and to use modern biological and chemical technologies to identify and develop novel molecules of therapeutic potential has opened several different possible avenues for the development of new therapeutic modalities such as immunotherapy or gene therapy.
Gene therapy aims to engineer a new vector system with a therapeutic gene in it that would be ideally suited for arresting metastatic progress of breast cancer. Such vectors would be designed to delivery a therapeutic gene only to target breast tumour cells.
1.5.2 Male Breast Cancer
Although it occurs infrequently, breast cancer can affect men as well as women. Male breast cancer is rare. Less than 1% of all breast carcinomas occur in men (Crichlow, 1990; Borgen et al., 1992; Crichlow, 1990). About 1,600 new cases were diagnosed in the United States in 1998 (Hultborn et al., 1997). According to the National Cancer Institutes (NCI) Surveillance, Epidemiology, and Results (SEER) Program, breast cancer affects 14 black men in every million and 8 men in every million overall (Ardyce et al., 1978). In Egypt, male breast cancer represents 6% of all breast cancer, and in Zambia it accounts for 15%. The mean age at diagnosis is between 60 and 70, although men of all ages can be affected with the disease.
The breast of the adult male is similar to the breast of a pre-adolescent girl (Roswit and Edlis, 1978; Willsher et al., 1997). It consists primarily of a few branching ducts lined by flattened cells surrounded by connective tissue. In girls, these cells and ducts develop in response to hormones secreted during puberty.
In males, too, breast tissue is capable of responding to hormonal stimulation. Enlargement of the male breast due to growth of the ducts and supporting tissues is known as gynocomastie.
Approximately 40 percent of all adolescent boys experience temporary breast enlargement, probably in response to hormones being secreted by the testes.
Predisposing risk factors (Jaiyesimi et al., 1992) appear to include radiation exposure, estrogen administration and diseases associated with hyperestrogenism, such as cirrhosis or Klinefelter‘s syndrome (Hultborn et al., 1997). There are definitive familial tendencies, with an increased incidence seen in men who have a number of female relatives with breast cancer. An increased risk of male breast cancer has been reported in families in which the BRCA2 mutation on chromosome 13q has been identified (Wooster et al., 1995; Thorlacius et al., 1995).
All of the types of breast cancer seen in women can occur in men, although some are quite rare.
The pathology is similar to that of female breast cancer, with infiltrating ductal cancer the most common tumour type (Harris et al., 1997), though intraductal cancer has also been described.
Inflammatory carcinoma and Paget‘s disease of the nipple have also been seen in men, but lobular carcinoma in situ has not (Harris et al., 1997). This is due to the fact that lobules are normally absent from the male breast.
The same procedures used to diagnose breast cancer in women can be used to diagnose breast cancer in men. These include medical history, physical examination, mammography and thermography. Even though the small male breast should facilitate early diagnosis, breast cancer in men has often spread before it can be diagnosed. Lacking the bulk of the typical female breast, even a small carcinoma in a male lies close to the skin above it and the tissues of the chest wall beneath it. Consequently, the cancer can more readily invade these nearby structures (Crichlow, 1972; Crichlow, 1977).
The treatment of male breast cancer is generally similar to the treatment of female breast cancer.
The basic therapy for primary cancer that shows no signs of distal spread is surgery. In advanced disease, it is hormonal therapy, chemotherapy or a combination of both or with radiotherapy.