BRCA mutation rate and characteristics of prostate tumor in breast and ovarian cancer families: analysis of 6,591 Italian pedigrees

Laura Cortesi; Federica Domati; Annalisa Guida; Isabella Marchi; Angela Toss; Elena Barbieri; Luigi Marcheselli; Marta Venturelli; Simonetta Piana; Claudia Cirilli; Massimo Federico

doi:10.20892/j.issn.2095-3941.2020.0481

BRCA mutation rate and characteristics of prostate tumor in breast and ovarian cancer families: analysis of 6,591 Italian pedigrees

Cancer Biol Med. 2021 Mar 12;18(2):470-476. doi: 10.20892/j.issn.2095-3941.2020.0481. Online ahead of print.

Affiliations

¹ Department of Oncology and Hematology, University Hospital of Modena, Modena 41124, Italy.
² Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena 41124, Italy.
³ Pathology Unit, Azienda USL Reggio Emilia, IRCCS, Reggio Emilia 42123, Italy.
⁴ Modena Cancer Registry, Public Health Department, AUSL Modena 41126, Italy.

PMID: 33710808
PMCID: PMC8185862
DOI: 10.20892/j.issn.2095-3941.2020.0481

Abstract

Objective: As prostate cancer (PrC) shows a BRCA mutation rate as high as 30%, it becomes crucial to find the optimal selection criteria for genetic testing. The primary objective of this study was to evaluate the BRCA mutation rate in families with PrC associated with breast and/or ovarian cancers; secondary aims were to compare the characteristics of families and BRCA-related PrC outcome among BRCA1 and BRCA2 carriers.

Methods: Following the Modena criteria for the BRCA test, we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score ≥7 PrCs, by testing breast or ovarian cases and inferring the mutation in the prostate cases. The characteristics of families and BRCA-related PrC outcomes were measured using the chi-square (χ²) test and Kaplan-Meier methods, respectively.

Results: Among 6,591 families, 580 (8.8%) with a Gleason score ≥ 7 PrCs were identified, of which 332 (57.2%) met the Modena selection criteria for BRCA testing. Overall, 215 breast or ovarian cancer probands (64.8%) were tested, of which 41 resulted positive for BRCA and one for CHEK2 genes (19.5%). No statistically significant differences were found in BRCA-related PrC prognosis and in the characteristics of families among BRCA1, BRCA2 and non-tested patients. Ten of 23 (44%) mutations in the BRCA2 gene fell in the prostate cancer cluster region (PCCR) at the 3´ terminal of the 7914 codon.

Conclusions: It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and PrC. A trend toward a worse prognosis has been found in BRCA2 carriers.

Keywords: BRCA genes; Modena criteria; breast cancer; hereditary cancer; ovarian cancer; prostate cancer.