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

Abstract

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 5 1.83, 95% confidence interval [CI] 5 1.75-1.90). Morphology-specific risks showed that relatives of LOB probands had an increased risk of LOB (FDR: FRR 5 4.51, 95% CI 5 2.79-6.89) and an increased risk of any BC (FDR: FRR 5 2.47, 95% CI 5 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. ' 2005 Wiley-Liss, Inc.Key words: breast cancer; lobular; familiality Family history is well-recognized as a strong risk factor for female breast cancer.1-7 First-degree female relatives of women with breast cancer have a 2-to 3-fold increased risk of breast cancer compared to the general population risk. The magnitude of breast cancer risk among relatives of a woman with breast cancer increases with her earlier age at onset, the number of other affected relatives in her family and their relationship to her. 8,9 In 2 separate meta-analyses of 52 and 74 breast cancer studies, the increased risk associated with one affected first-degree relative ranged from 1.8-3.3-fold depending on whether the relative was a mother or a sister and whether diagnosis occurred at <50 years of age. 8,9 Breast cancer risk estimates varied up to 3.9-fold by having 3 affected first-degree relatives. 9Breast cancer is a mix of morphologically distinct cancers. Attempts to determine whether the increased risk for breast cancer varies by morphological subtype have met with limited success in the past. Before the discovery of the breast cancer predisposing gene BRCA1, it was reported that relatives of those with medullary breast carcinomas were at increased risk of breast cancer. [10][11][12] BRCA1 mutations have since been shown to be associated with an excess of medullary and atypical medullary cancers, 13,14 and more recently, the basal epithelial subtype.15-17 Alt...

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“…The association between breast cancer and a family history of breast cancer observed in our study may be partially attributed to inherited genetic susceptibility. A number of genes that have been identified during the past 10 years, most notably the BRCA1 and BRCA2 genes, have been linked to breast carcinogenesis [1,8,11,12,26]. Mutations in BRCA1 and BRCA2 are associated with 10-fold or more increased risk of breast cancer [12].…”

Population-Based Family History–Specific Risks for Colorectal Cancer: A Constellation Approach

“…This ratio, also known as a ‘standardized morbidity ratio’, is considered a reasonable approximation of true relative risk when the prevalence of the disease and the true relative risk in the population are low 23. This method of estimating FRR in relatives has been used in previous UPDB analyses of familial risk in cancer 24,25 and other diseases. 26,27…”

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