Cancer of the breast is the most important malignant disease affecting women in the industrialized world. It is the principal cause of cancer morbidity and mortality in the United States, with 192,200 new cases and 40,200 deaths estimated for the year 2001 (Greenlee et al, 2001). The most important risk factor is a history of breast cancer in close relatives. A small number of patients come from families that have mutations of the breast cancer genes BRCA1 and BRCA2, and perhaps other genes as well (Lakhani et al, 1998; Loman et al, 1998, 2000; Haber, 2000; Hedenfalk et al, 2001; Ziv et al, 2001). The risk of breast cancer is minimally increased in women who take hormonal contraceptives, but this risk is no longer present 10 years after cessation of medication (Collaborative Group on Hormonal
Factors in Breast Cancer, 1996). However, treatment with estrogen and progestin for symptoms of menopause constitute an important risk factor, regardless of whether the treatment is of short or long duration (Chlebowski et al, 2003; Li et al, 2003b). Heritability of mammographic densities has also been tentatively suggested as a risk factor (Boyd et al, 2002).

Breast cancer has a well known and much studied natural history. The morphologically recognizable initial stages of breast cancer are carcinomas in situ that are confined to breast ducts or lobules, or both. It is evident that a major upheaval in cell proliferation genes, such as p53, must occur before the tumor develops, but very little is known about these early events (Haber, 2000). Invasive breast cancer is derived from carcinoma in situ; however, the precise rate of progression is unknown. Once invasion has occurred, breast cancer can metastasize to regional axillary lymph nodes and beyond.

Staging reflects the extent of the spread of breast cancer. According to the TNM (tumor, lymph nodes, metastases) classification system, carcinomas in situ are classified as Tis; tumors that are limited to the breast and are no larger than 2 cm in diameter are T1; larger tumors limited to the breast are T2 or T3, and tumors with evidence of metastatic spread are T4 (Rosen, 2001). The concept of sentinel lymph node (SLN), i.e., the axillary lymph node most likely to harbor metastatic cancer, as identified by tracing substances (a blue dye or radioactive colloid, or both, injected into the breast), has become important in assessing treatment options (Giuliano et al, 1994, 1995; Fraile et al, 2000; McMasters et al, 2000). An SLN containing metastatic cancer documents that the disease has spread beyond the breast into the homolateral axillary lymph nodes.

The behavior and prognosis of breast cancer are generally stage related.

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