Hereditary Pancreatic Cancer: A Retrospective Single-Center Study of 5143 Italian Families with History of BRCA-Related Malignancies.

Toss A1, Venturelli M2, Molinaro E3, Pipitone S4, Barbieri E5, Marchi I6, Tenedini E7,8, Artuso L9,10, Castellano S11, Marino M12, Tagliafico E7,8, Razzaboni E13, De Matteis E14, Cascinu S15, Cortesi L16.

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Abstract

The identification of BRCA mutations plays a crucial role in the management of hereditary cancer prevention and treatment. Nonetheless, BRCA-testing in pancreatic cancer (PC) patients is not universally introduced in clinical practice. A retrospective analysis was conducted, firstly, to evaluate the rate of BRCA-positive families among those presenting a family history of PC besides breast and/or ovarian cancer. Secondly, the relationship between BRCA pathogenic variants and PC risk was evaluated. Finally, the characteristics of PC developed in BRCA families were described. Among 5143 family trees reporting breast and/or ovarian cancer cases, 392 showed a family history of PC. A total of 35 families (24.5% selected by the Modena Criteria and 21.3% by the NCCN Criteria) were positive to BRCA testing. Among the BRCA1 mutations, 36.8% were found within a region defined by c.3239⁻c.3917, whilst 43.7% of BRCA2 mutations were located within c.7180⁻c.8248. This study confirmed that an increase in the rate of positive tests in families with PC when associated to breast and/or ovarian tumors. Moreover, this analysis indicated two possible Pancreatic Cancer Cluster Regions that should be verified in future research. Finally, PC in families with breast and/or ovarian cancer history, particularly in BRCA families, were diagnosed at younger age and showed better one-year overall survival.