Lobular breast cancer: excess familiality observed in the Utah Population Database

Family history of breast cancer (BC) is a strong predictor for developing female BC. Whether this excess familiality differs within morphological BC subgroups remains unclear. We assessed the risk of lobular breast cancer (LOB) and any BC among relatives of probands with LOB. We used the Utah Population Database (UPDB) to estimate familial relative risks (FRR) as well as average relatedness, using the genealogical index of familiality (GIF) statistic. The UPDB, a population-based resource, links genealogical data from over 2 million individuals to the Utah Cancer Registry. Consistent with other studies, analysis of all BC cases showed significantly increased risk of BC to relatives (first-degree relative [FDR]: FRR = 1.83, 95% confidence interval [CI] = 1.75-1.90). Morphology-specific risks showed that relatives of LOB probands had an increased risk of LOB (FDR: FRR = 4.51, 95% CI = 2.79-6.89) and an increased risk of any BC (FDR: FRR = 2.47, 95% CI = 2.12-2.85); both measures were significantly greater than the all BC FRR estimates, and surpassed even generalized early-onset BC risk. GIF analyses corroborated the FRR results and indicated that the excess relatedness of LOB cases extended to third-degree relatives. Our findings suggest that LOB has a heritable component and may represent a genetically homogeneous form of BC. Pedigrees with excess LOB may be useful in isolating additional BC predisposition genes. Relatives of women with LOB are at higher risk for BC than relatives of other BC subtypes; a more rigorous BC screening regime may be warranted for these individuals.