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FOUNDATION OVERVIEW

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Mutations of genes controlling cell proliferation and apoptosis are the primary cause of neoplastic disease, 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 fivefold increased risk for the development of breast cancer (lifetime risk increases from 12% to 40%-60%). In addition, prolonged exposure to estrogen (early menarche, nulliparity, late first pregnancy, late menopause) and age older than 40 have been established as risk factors for breast cancer.

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Clinical Presentation/Diagnosis

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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.

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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 (HER2). These biologic markers are prognostic for a patient responding to drugs that target these receptors.

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Pharmacotherapy Overview

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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 breast tumor of 2 cm or less 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 greater than 5 cm, even though lymph nodes do not contain cancer. Stage III breast cancer exists when either the primary tumor extends into the chest wall or when regional lymph nodes are fixed to surrounding tissue (immobile). Stage IV disease is present when the tumor cells have invaded distant tissue (metastatic disease). Common sites of breast cancer metastases include the bone, liver, and lungs. Survival of women with ...

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