has a circular areola. The nipple is also comprised of oil and sweat glands, and there is a high concentration of sensory nerve endings as well.
Stem Cells in the Breast
Adult stem cells, medically referred to as somatic stem cells (SSC), are located in various organs throughout the body. Somatic stem cells are undifferentiated cells that have the unique ability to divide into two identical daughter cells or to transform into specialized cells. This choice between self-renewal or differentiation is determined by the environment. These rare somatic stem cells are essential to renew and to repair tissues, but the self-renewal properties of somatic stem cells can increase their chances of becoming cancer cells.
Mutations of Stem Cells
When somatic cells replicate and divide, both point and chromosomal mutations accumulate with each additional generation of daughter cells because the replicative machinery commits errors and because of exposure to mutagenic agents. These mutations can have significant influences on cellular birth and death rates depending on the nature of the mutation. When comparing normal somatic cells with mutated somatic cells, it is important to realize that normal somatic cells grow, replicate, and die only when they receive specific signals. However, point or chromosomal mutations can allow somatic stem cells to create their own growth signals, to respond to signals destined to other cells, or to escape signals that cause normal cells to die by a process called apoptosis.
Mutations that increase the growth rate of somatic cells or that allow them to escape normal regulatory signals give them a selective advantage that allows them to outcompete their normal counterparts. As more genetic mutations occur, more functions in the cells can be affected. These malfunctions include disregulation of proto-oncogenes that stimulate cell growth, tumor-suppressor genes that suppress cell growth, and apoptosis genes that control cell death. The cumulative effect of these malfunctions leads to initial tumor formation.
Cancers of the Breast
Breast cancers are classified by two major categories depending on where they originate in the breast. Malignant breast tumors are common in postmenopausal women and arise from mammary duct epithelium or lobular glands. They are usually the result of overexpression of estrogen and progesterone receptors or erb-B2 (or HER-2, an epidermal growth factor receptor). Axillary lymph node involvement is the single most important prognostic factor in breast cancer. Risk factors for malignant breast tumors include increased exposure to estrogen.
The majority of patients with breast cancer have cancer that originated in the milk ducts of the breast. This type of cancer is called ductal carcinoma, and there are two subtypes: invasive and noninvasive. The noninvasive type of ductal carcinoma is named ductal carcinoma in-situ (DCIS). This type of cancer arises from ductal hyperplasia, which fills the ductal lumen and is considered noninvasive because it does not spread to other tissues of the breast. The second type of ductal carcinoma is named invasive ductal carcinoma and is characterized by the spread of the cancer through the walls of the milk ducts into other tissues of the breast. This results in a firm, fibrous, hard mass with sharp margins and small, glandular duct cells. Invasive ductal carcinoma is the most invasive and most common, accounting for over 75% of breast cancers.
The second major category of breast cancers comes from cancers that originate in the lobules of the breast. The lobules are the parts of the breast responsible for lactation, or the production of milk. Cancers of this type are called lobular carcinomas. Similar to ductal carcinoma, lobular carcinoma contains also two subtypes of the cancer: lobular carcinoma in-situ and invasive lobular carcinoma. Invasive lobular carcinoma is similar to invasive ductal carcinoma in that it spreads outside the lobules of the breast into other tissues. It differs, though, in that there is not a lump that is associated with the cancer. Instead of creating a lump, the cancer cells cause the tissues of the breast to thicken. There are often multiple lumps, and it is often bilateral. Women diagnosed with invasive lobular carcinoma may experience a firmness or unusual fullness of the breast. Lobular carcinoma in-situ differs from the other types of cancers in that it is not, in fact, a cancer. Although there is a presence of abnormal cells in the lobules of the breast, they are noncancerous. Receiving a diagnosis of lobular carcinoma in-situ is certainly better than other types of breast cancers. Although lobular carcinoma in-situ is noncancerous, it does indicate a considerably higher risk for the patient to develop another type of breast cancer. Although these are the two principal categories of origination for breast cancers, there are rare occurrences in which the cancer originates from areas other than the milk ducts and lobules.
Medullary breast cancer demonstrates lymphatic infiltrate on histology and has good prognosis. Comedocarcinoma is a subtype of DCIS that involves ductal caseous necrosis. Lymphatic dermal invasive by breast carcinoma is known as inflammatory breast cancer. This type of breast cancer is characterized by the skin turning into a texture that resembles an orange peel (and is commonly termed peau d’orange). The survival rate for this type of cancer at five years is approximately 50%. Paget’s disease of the breast presents with eczematous patches on the nipple and is a sign for an underlying carcinoma.
Other Major Pathologies of the Breast
One common abnormality of the breast found in both men and women is polythelia, also known as supernumerary nipple. Polythelia is characterized by the presence of more than the normal number of two nipples. Although supernumerary nipples can be found anywhere on the body, they are most often found on the milk line, which extends from the armpit to the groin. Although not harmful, supernumerary nipples are often removed by excision because they can develop the same diseases as normal nipples.
Another common pathology of the breast is sclerosing adenosis. Sclerosis refers to a condition where the tissues in the breast harden, leading to sclerosing adenosis as well as complex sclerosing lesions or radial scars. This disease is characterized by the presence of additional tissue in the breast lobules, which can cause lumps and discomfort. Although these lumps are noncancerous, the pain associated with it sometimes gives reason for the lumps to be removed. Sclerosing adenosis is more commonly seen in women in their thirties and forties, and occur naturally as a woman ages. Although some women do experience pain that may lead to the excision of the lump, many others experience no symptoms and their condition can go unnoticed. Due to how the disease manifests itself, however, once a lump is found, most times physicians opt to obtain a biopsy of the lump to check for cancerous tumors, which are similar to the lumps of sclerosing adenosis. Complex sclerosing adenosis and radial scars are both similar to sclerosing adenosis in that they are characterized by hardening of breast tissue, and are found primarily in older women. They differ from one another only on the account of size: any lump smaller than 1 centimeter is classified as a radial scar and lumps bigger than 1 centimeter are classified as complex sclerosing lesions.
A third relatively common pathology of the breast is fibrocystic disease. Fibrocystic breasts are characterized as breasts that contain tissue that is said to be lumpy, causing unevenness of the breast and discomfort or pain. The lumpiness in the breasts is caused by noncancerous masses within the breasts, which may be cysts or masses of hardened tissue. Classically, fibrocystic disease presents with premenstrual breast pain involving multiple lesions in both breasts. These lesions also fluctuate in size. Fibrocystic breasts are common in women, especially before menstruation or during later years in a woman’s life, however it generally declines after a woman experiences menopause. Today, physicians are leaning away from considering fibrocystic breasts as a disease due to the fact that over half of women in the United States are affected by it. In addition, the masses do not indicate an increased risk of carcinoma. Histologic types include fibrosis (hyperplasia of the breast stroma), cystic (fluid filled with ductal dilation), sclerosing adenosis (increased acini with intralobular fibrosis), and epithelial hyperplasia (increased number of epithelial cell layers in the terminal duct lobule; this type, which presents in women over 30 years of age,
