While lifestyle factors no doubt contribute to the incidence of breast cancer in families with multiple instances of breast cancer, genetic factors are also at work. Women with a family history of breast cancer tend to have high breast density, which is a strong and highly heritable breast cancer risk factor. Familial breast cancer tends to be more aggressive than nonfamilial breast cancer and women in such families are more likely to get breast cancer at a younger age than those without such as history. Women whose mothers died of breast cancer are also more likely to die from it, even adjusting for tumor characteristics. Women in such families are more likely to develop benign fibrocystic breast disease, another breast cancer risk factor. Now a new study has reported that the genetic factors underlying familial breast cancer can be family-specific. In other words, a given risk-related genetic profile can be rich in an affected family, but not found in other families with multiple occurrences of breast cancer.

Latest research finds genetic factors may be family-specific

The study referenced at the beginning of this news article was designed to investigate the genetic predisposition to breast cancer in a family with five cases of breast cancer, none of whom had harmful BRCA1, BRCA2, p53, or PTEN mutations. While familial clustering of breast cancer is common, little progress has been made in identifying specific genetic factors underlying the tendency to develop breast cancer in the majority of such families. To conduct the study, the authors sequenced the entire coding region of the genome for eight members of one such family (of whom five had breast cancer).

A total of 55 nonsynonymous germline variants affecting 49 genes in multiple members of the family were identified. Of these variants, 22 were predicted to have damaging effects. Two variants in one gene (KAT6B, an acetal transferase gene) were identified in six family members, of which five were affected with breast cancer (and one is an unaffected carrier).

The authors then searched for the identified germline variants in 40 breast cancer cases in 22 other familial breast cancer families. However, none of the 22 variants was found in these other families. The authors conclude that the genetic predisposition for familial breast cancer can be family-specific — a given genetic profile can be rich in an affected family, but not found in others. Therefore, it will be difficult to detect genetic factors associated with breast cancer in such families by applying a population-based approach. In fact, it might be necessary to study each affected family to determine the basis for its genetic predisposition toward breast cancer.

Please see our article on familial breast cancer for information on the degree of additional risk conferred by having family members with breast cancer.