Introduction
Although noninherited factors certainly play a major role in familial clustering of breast cancer, breast cancer susceptibility genes appear directly responsible for 5% to 10% of all breast cancer. Much remains to be understood about the heritable factors involved; however, enormous strides have been made in understanding inherited susceptibility to breast cancer with the discovery and characterization of a number of genes responsible for the clustering of breast cancer in certain families. Nevertheless, almost nothing is known about the interaction of various genes and the interaction of genes and environmental factors, both exogenous (e.g., pesticides) and endogenous (e.g., estrogen).

Among women, breast cancer is the most commonly diagnosed cancer after nonmelanoma skin cancer, and is the second leading cause of cancer deaths after lung cancer. In 2008, an estimated 182,460 new cases will be diagnosed, and 40,480 deaths from breast cancer will occur. The incidence of breast cancer, particularly for estrogen receptor-positive cancers occurring after age 50 years, has declined at a faster rate since 2003; this may be temporally related to a decrease in hormone replacement therapy following early reports from the Women’s Health Initiative. Ovarian cancer is the eighth most common cancer, with an estimated 21,650 new cases in 2008, but is the fifth most deadly, with an estimated 15,520 deaths in 2008.

A possible genetic contribution to both breast and ovarian cancer risk is indicated by the increased incidence of these cancers among women with a family history, and by the observation of rare families in which multiple family members are affected with breast and/or ovarian cancer, in a pattern compatible with autosomal dominant inheritance of cancer susceptibility. Formal studies of families (linkage analysis) have subsequently proven the existence of autosomal dominant predispositions to breast and ovarian cancer and have led to the identification of several highly penetrant genes as the cause of inherited cancer risk in many cancer-prone families. Mutations in these genes are rare in the general population and are estimated to account for no more than 5% to 10% of breast and ovarian cancer cases overall. It is likely that other genetic factors contribute to the etiology of some of these cancers.

Less than 10% of breast cancer cases are genetically inherited. Most women diagnosed with breast cancer do not have a family history of the disease.

If you have a first-degree relative (parent, sibling or child) who has had breast cancer, you have an increased risk of developing breast cancer.

If you have a family history with one or more first-degree relatives who have had cancer in both breasts (bilateral breast cancer), particularly before menopause, you may have genetically inherited breast cancer. A genetic counselor can help you assess your risk, and the risk of others in your family.

Your risk of not developing breast cancer in your lifetime is much greater than your risk of developing breast cancer. Remember to always talk to your doctor about your breast cancer concerns.

Angela DeMichele and Barbara L. Weber

A. DeMichele: Departments of Medicine and Epidemiology, The University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania
B. L. Weber: Departments of Medicine and Genetics, Breast Cancer Program, Population Science and Cancer Control, The University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania

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