FEATURED , Research , Subtypes

Alan Stolier, MD/


Familial Clustering Pedigree

                  Pedigree with familial clustering of mucinous carcinoma 


Though a majority of breast cancers are ductal carcinomas, many subtypes exist. More specifically, mucinous carcinomas account for only 1-2% of breast cancers and have a better than average prognosis. It has been demonstrated to have a lower level of genomic instability. On the other hand, inflammatory breast cancer carries a worse prognosis but is not necessarily defined by histologic subtype. Inflammatory breast cancers account for approximately 2.5% of cases.

Approximately 5-10% of breast cancer cases are inherited. However, the only histologic subtype associated with a specific histologic subtype is lobular carcinoma with CDH1, which encodes for the cadherin genes. Recent reports have suggested that there may be familial clustering in inflammatory breast cancer with a suggestion of a likely germline mutation (see Breast Care Network post on Inflammatory Cancer and Germline Mutation Risk). 

In a recent study published in the journal Cancer, N. Lynn Henry and Lisa Cannon- Albright from the University of Utah studied the familial clustering of histologic subtypes. The authors used the Genealogical Index of Familiarity in retrieving evidence that a specific cancer is mediated by genetic factors. Determining whether a cancer has familial clustering might potentially be used to calculate risk, understand pathogenesis and identify specific mutations. The authors used the Utah Population Database which has identified approximately 3 million people with between 3 and 16 generations of genealogy data. Approximately 150,000 of the 3 million individuals have a link to the Utah Cancer Registry with 23,629 having been diagnosed with breast cancer.

The results showed that 3 breast cancer subtypes had familial clustering. They found 48 high-risk inflammatory breast cancer pedigrees including between 2 and 4 inflammatory cancer cases. They found 110 high-risk mucinous cancer pedigrees containing between 2 and 13 mucinous cancers (one such pedigree can be seen in the figure above). Finally, they identified 273 high-risk lobular breast cancer including between 2 and 14 related lobular cases.

They found no evidence of clustering of other breast cancer subtypes. Including invasive ductal carcinoma. Somewhat surprisingly, they found no familial clustering of medullary carcinoma despite its known association with BRCA1. It has been reported elsewhere that only about 11% of patients with medullary carcinoma had pathologic variants in BRCA1.

In conclusion, the authors were able to identify 3 breast cancer subtypes with familial clustering. These included lobular, mucinous and inflammatory breast cancers. This study suggests that although modest, the relative risk of these histologic subtypes appear to cluster in pedigrees more than expected. This finding may assist in identifying predisposition genes responsible for these histologies and furthermore help in identifying potential etiologies.

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