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Breast cancer histologic subtypes show excess familial clustering
  • Published Date:
    May 23 2019
  • Source:
    Cancer. 125(18):3131-3138
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Public Access Version Available on: September 15, 2020 information icon
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  • Description:

    The inherited predisposition to development of specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. Using a large, population-based database, we sought to investigate familial clustering of breast cancer by histologic subtype.


    Using the Utah Population Database (UPDB), which links genealogy records to the state-wide National Cancer Institute Surveillance, Epidemiology, and End-Results cancer registry, we identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating relative risk (RR) among first-, second-, and third-degree relatives.


    We identified 23,629 individuals in the UPDB with at least 3 generations of genealogy and at least one primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n=178], lobular [n=1688], and mucinous [n=542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (p=0.011) as well as for inflammatory breast cancers (p=0.024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR 1.32 [1.02, 1.68]; p=0.03), lobular (RR 1.36 [1.25, 1.47]; p<0.001), and mucinous (RR 1.27 [1.12, 1.44]; p=0.00021) subtypes.


    These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.

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