Epidemiologic Studies of Familial Breast Cancer

The first attempts to determine the influence of family history on breast cancer risk were published in the first half of the twentieth century. Although many of these studies have methodological flaws, they consistently demonstrated a twofold to threefold increase in breast cancer risk in mothers and sisters of breast cancer patients. The largest population-based study to estimate breast cancer risk associated with a family history was a study conducted in Sweden that involved 2,660 women. Within this study cohort, women with an affected relative had a relative breast cancer risk of 1.7. Relative risks of a similar magnitude were found in a Canadian population-based study and in the U.S. Nurses' Health Study.

Preliminary data from the population-based Carolina Breast Cancer Study have been released recently. Although information on controls has not yet been published, in this series, 20% of individuals with breast cancer reported a first-degree relative with breast cancer, and 49% reported breast cancer in at least one relative of any type. Although information on controls is needed before relative risks of family history in this cohort can be calculated, the familial component to breast cancer is likely to be even greater than has been appreciated in the past.

These data also suggest that increased breast cancer incidence in this population compared with that in the previously cited historical studies, as well as increases in both public awareness and the likelihood that women will discuss a diagnosis of breast cancer with family members, has contributed to higher reporting of affected family members.

Anderson was among the first to suggest that breast cancer was not a homogeneous disease and that the occurrence of breast cancer was not influenced by genetic factors in a uniform manner. In such a setting, a small subset of families with a very high risk of developing breast cancer as the result of a single genetic defect might be obscured in studies in which the majority of breast cancer cases were multifactorial in origin.

To emphasize the hereditary component, Anderson therefore assembled a database enriched for kindreds with a family history of breast cancer. The primary factors that increased risk within families were premenopausal status at time of diagnosis and bilateral disease.

By 1980, a significant body of evidence had accumulated to support the presence of inherited factors responsible for familial clustering of breast cancer, and efforts shifted to determining the inheritance pattern of breast cancer within these families. In 1984, Williams and Anderson examined 200 Danish pedigrees and provided the first evidence for an autosomal dominant breast cancer susceptibility gene with an age-related penetrance, as was supported in 1988 by Newman et al.

Angela DeMichele and Barbara L. Weber

A. DeMichele: Departments of Medicine and Epidemiology, The University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania