http://evolve.elsevier.com/Edmunds/NP/
This chapter briefly discusses the hormonal treatment of patients with breast cancer. A full discussion is beyond the scope of this book. The goal of the chapter is to familiarize the primary care provider with the medications that some patients may be taking for the treatment of breast cancer. Most of these drugs are given on a long-term daily schedule and may interact with other medications prescribed for chronic disease or acute illnesses.
Therapeutic Overview
The following is a very brief discussion of breast cancer.
Anatomy and Physiology
Approximately 5% to 10% of breast cancers have a familial or genetic link. Mutations in the BRCA family of genes confer a lifetime risk of breast cancer that approaches 85%. BRCA1 and BRCA2 are the main genes involved. These genes also increase the risk of ovarian cancer. The breast cancer that occurs in women >50 years of age or in postmenopausal women is often hormone receptive. Tamoxifen has been found to delay cancer return for more than a decade, and women taking the drug had one third lower risk of dying.
Pathophysiology
Two main categories of breast cancer have been identified. The first is ductal carcinoma in situ (DCIS), which starts in the ductal epithelium. It is considered in situ when it has not penetrated the base membrane and is usually found in older women. Most of these cancers have infiltrated and spread by the time of discovery. This is the most common type of cancer, although the histology of these cancers is varied. The second type of cancer is lobular cancer, which consists of uniform small, round neoplastic cells that are slower to infiltrate. Among these two major categories of cancer are a variety of histologic types. For example, inflammatory cancer is rare but highly malignant. It is rapid growing and characterized by inflammation of the skin. Breast cancer is divided into four classes for optimal selection of treatment: (1) DCIS, (2) primary operable breast cancer, (3) locally advanced breast cancer, and (4) breast cancer with metastasis.
Assessment
Much research has been related to risk factors, and new ones have been discovered. Box 56-1 lists the well-established risk factors. A breast cancer risk calculator can be found at http://www.cancer.gov/bcrisktool. It also can be obtained by calling 800-4-CANCER, or through AstraZeneca Pharmaceuticals, which manufactures tamoxifen.
Self-breast examination and mammography are effective in screening for early breast cancer. Screening mammography reduces breast cancer mortality by about 33% in women 50 to 70 years old. However, effectiveness is less well established for women younger than 50 years of age. The American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists have agreed that all women should undergo annual screening mammography beginning at age 40.
Mechanism of Action
Tamoxifen is a nonsteroidal selective estrogen receptor modulator (SERM; see Chapter 39, Osteoporosis Treatment). It competes with estradiol at binding sites in the cell nucleus in breast tissue, altering gene transcription and protein synthesis. This inhibits the growth of estrogen-dependent tumor cells. Tamoxifen acts as an estrogen agonist and has a favorable effect on plasma lipid levels and bone mineral density. However, it may be linked to endometrial malignancy and thromboembolism.
Fulvestrant is an estrogen receptor antagonist that competes with estradiol by binding to estrogen receptors. This medication helps to downregulate the ER protein in human breast cancer cells.
Toremifene binds to estrogen receptors and exerts an antiestrogenic effect. It competes with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor.
Aromatase Inhibitors
Anastrozole blocks the aromatase enzyme from converting androstenedione to estrone and testosterone to estradiol. Many breast cancers also contain aromatase. Anastrozole is a potent and selective nonsteroidal aromatase inhibitor; it lowers serum estradiol concentrations.
Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the aromatase enzyme, resulting in reduction of estrogen biosynthesis in all tissues. It is a more potent inhibitor of the aromatase enzyme than is anastrozole.
Exemestane is a steroidal aromatase inactivator. It acts as a false substrate for the aromatase enzyme that binds irreversibly to the active site of the enzyme, causing its inactivation. This results in decreased circulating estrogen concentrations.
Treatment Principles
Multiple guidelines are available. See the National Guideline Clearinghouse at www.guideline.gov, or the National Comprehensive Cancer Network Clinical Practice Guidelines at www.NCCN.org.
Evidence-Based Recommendations
Local Breast Cancer—Nonmetastatic
(Recommendations may vary depending on whether the patient is premenopausal or postmenopausal.)
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