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In 1860, Dr. Broca, a French surgeon, reported on the pedigree of his wife's family because of her early-onset breast cancer and the striking family history of breast cancer.1 At around the same time, in 1865, Dr. Gregory Mendel was looking at the genetics of garden peas; his work would lay the foundation for the field of genetics. In the last 150 years, the identification and recognition of the molecular genetics component of disease has advanced, and the area of breast cancer has been no exception. Molecular genetic testing is redefining familial cancer and will continue to do so for many years. This chapter will review the clinical features, causative genes, and medical management options for hereditary breast cancer syndromes.

It has been estimated that 23% of all breast cancer patients have a family history of the disease, indicating that one or more first-degree relatives have been diagnosed with breast cancer in the family (Fig. 8-1).2 In the general population, only 2% of all women have a family history suggestive of the inheritance of an autosomal dominant, inherited high-penetrance gene for breast cancer.2 When you look specifically at breast cancer patients, only 5% to 10% of all breast cancer cases demonstrate a clear pattern of dominant inheritance.4 There are several highly penetrant, dominantly inherited genes associated with breast cancer predisposition syndromes, including the BRCA1, BRCA2, TP53, and PTEN genes (Fig. 8-2). Although these cancer predisposition syndromes are rare, the clinician needs to be aware of these hereditary cancer syndromes that predispose to the carcinoma of the breast, and to recognize the diversity of these unique syndromes. However, most cases of familial breast cancer are not attributed to these single-gene disorders. It is believed that may are due to unidentified, low-penetrant genetic mutations and/or variants in the genome, in combination with environmental factors. The identification of these low-penetrant alleles is the next frontier for cancer genetics.

Figure 8-1

Percentage of breast cancer patients with a family history of breast cancer.

Figure 8-2

Percentage of breast cancer cases with a genetic mutation.

The American Society of Clinical Oncology recommends that genetic testing be offered when three criteria are met: (1) the individual has a personal or family history suggestive of a cancer genetic susceptibility condition, (2) the test can be adequately interpreted, and (3) the results will aid in the diagnosis or influence the medical or surgical management of the patient or family members.5 These recommendations begin with the identification of these high-risk patients. A comprehensive review of family history is key to identifying patients at increased risk for hereditary cancer. In obtaining a 3-generation family history, it is important not only to elicit the family history of breast cancer, but to also ask about other cancers, including ...

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