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FOUNDATION OVERVIEW

Mutations of genes controlling cell proliferation and apoptosis are the primary causes of neoplastic diseases and specific gene mutations (BRCA1, BRCA2, p53, PTEN) have been identified in breast cancer. Women with mutations in the tumor suppressor genes BRCA1 and BRCA2 have a four- to five-fold increased risk for the development of breast cancer (approximate lifetime risk increases from 12% to 45%-65%). In addition, family history, prolonged exposure to estrogen (early menarche, nulliparity, late first pregnancy, late menopause), and age over 40 have been established as risk factors for breast cancer.

Clinical Presentation/Diagnosis

Prior to the development of mammography, breast cancer was 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.

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 are 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 the surface of the breast cancer cells. Specifically, the pathology report will determine 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 patient responding to drugs that target these receptors.

Following a positive pathologic review, various imaging strategies (eg, computed tomography [CT] scan, magnetic resonance imaging [MRI], positron-emission tomography [PET] scan, bone scan) are conducted to determine the extent of cancer spread and disease stage.

Pharmacotherapy Overview

The stage of a patient’s breast cancer is determined by the size of the primary lesion (T), whether regional lymph nodes contain micrometastatic cancer (N), and whether metastatic disease is present (M). Stage I breast cancer is characterized by a breast tumor less than or equal to 2 cm and regional lymph nodes that do not contain micrometastatic cancer. Stage II breast cancer exists when regional lymph nodes contain cancer or when the primary lesion is more than 5 cm, even though lymph nodes do not contain cancer. Stage III breast cancer exists when either the primary tumor extends into the ...

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