Breast cancer is the most prevalent malignancy in US women. It was estimated that approximately 192,000 US women were diagnosed with breast cancer in 2009. This number represents approximately 27% of all new cancer cases diagnosed in US women annually. Moreover, in 2009 an estimated 40,000 US women died of breast cancer making it the second leading cause of death from cancer after lung cancer. Breast cancer rarely affects men (2009 US estimates: 1910 new cases, 440 deaths). While breast cancer causes significant morbidity and mortality, death from breast cancer in the United States has been gradually declining since the early 1990s. The implementation of early detection guidelines and effective adjuvant therapy have been identified as approaches resulting in this positive trend.1,2
Mutations of genes controlling cell proliferation and apoptosis have been established as a primary cause of neoplastic disease. Specific gene mutations (BRCA1, BRCA2, p53, PTEN) have been identified in patients with breast cancer. Women with mutations in the tumor suppressor genes BRCA1 and BRCA2 have a four- to fivefold increased risk for the development of breast cancer (lifetime risk increases from 12% to 40%-60%).3-6 In addition, prolonged exposure to estrogen (early menarche, nulliparity, late first pregnancy, late menopause) and age over 50 have been established as risk factors for breast cancer.7
Prior to the development of mammography, breast cancer was often diagnosed after a tissue biopsy of a painless breast mass that was palpated during self or clinical breast examination. The increased survival and improved quality of life for women whose breast cancer was diagnosed before it had spread to lymph nodes (micrometastatic disease) or to distant organs (metastatic disease) led to efforts to increase early detection of localized breast cancers. Since the widespread implementation of screening mammography guidelines in the mid-1980s, the majority of breast cancers are diagnosed after tissue biopsy of a suspicious lesion identified by mammography. The efficacy of mammography to detect breast cancer prior to the development of clinically detectable disease is supported by decreased death rates.8,9
After a breast mass is identified, the diagnosis of breast cancer is made by microscopic examination of a tissue biopsy. Breast cancers are categorized by the histologic and biologic characteristics of the cells present in the biopsy specimen. They arise from lobular and ductal epithelial cells and thus classified as adenocarcinomas. Furthermore, adenocarcinomas of the breast are classified as in situ (cancer confined to site of origin) or invasive (cancer that has spread through tissue barriers and invaded surrounding areas). The pathologic description of breast adenocarcinoma also includes the quantification of receptors present on surface of the breast cancer cells. Specifically, the pathology report will specify the level of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). These biologic markers are prognostic for a ...