Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Authors:
Valentina Silvestri Goska Leslie Daniel R Barnes Bjarni A Agnarsson Kristiina Aittomäki Elisa Alducci Irene L Andrulis Rosa B Barkardottir Alicia Barroso Daniel Barrowdale Javier Benitez Bernardo Bonanni Ake Borg Saundra S Buys Trinidad Caldés Maria A Caligo Carlo Capalbo Ian Campbell Wendy K Chung Kathleen B M Claes Sarah V Colonna Laura Cortesi Fergus J Couch Miguel de la Hoya Orland Diez Yuan Chun Ding Susan Domchek Douglas F Easton Bent Ejlertsen Christoph Engel D Gareth Evans Lidia Feliubadalò Lenka Foretova Florentia Fostira Lajos Géczi Anne-Marie Gerdes Gord Glendon Andrew K Godwin David E Goldgar Eric Hahnen Frans B L Hogervorst John L Hopper Peter J Hulick Claudine Isaacs Angel Izquierdo Paul A James Ramunas Janavicius Uffe Birk Jensen Esther M John Vijai Joseph Irene Konstantopoulou Allison W Kurian Ava Kwong Elisabetta Landucci Fabienne Lesueur Jennifer T Loud Eva Machackova Phuong L Mai Keivan Majidzadeh-A Siranoush Manoukian Marco Montagna Lidia Moserle Anna Marie Mulligan Katherine L Nathanson Heli Nevanlinna Joanne Ngeow Liene Nikitina-Zake Kenneth Offit Edith Olah Olufunmilayo I Olopade Ana Osorio Laura Papi Sue K Park Inge Sokilde Pedersen Pedro Perez-Segura Annabeth H Petersen Pedro Pinto Berardino Porfirio Miquel Angel Pujana Paolo Radice Johanna Rantala Muhammad U Rashid Barak Rosenzweig Maria Rossing Marta Santamariña Rita K Schmutzler Leigha Senter Jacques Simard Christian F Singer Angela R Solano Melissa C Southey Linda Steele Zoe Steinsnyder Dominique Stoppa-Lyonnet Yen Yen Tan Manuel R Teixeira Soo H Teo Mary Beth Terry Mads Thomassen Amanda E Toland Sara Torres-Esquius Nadine Tung Christi J van Asperen Ana Vega Alessandra Viel Jeroen Vierstraete Barbara Wappenschmidt Jeffrey N Weitzel Greet Wieme Sook-Yee Yoon Kristin K Zorn Lesley McGuffog Michael T Parsons Ute Hamann Mark H Greene Judy A Kirk Susan L Neuhausen Timothy R Rebbeck Marc Tischkowitz Georgia Chenevix-Trench Antonis C Antoniou Eitan Friedman Laura Ottini

JAMA Oncol 2020 Aug;6(8):1218-1230

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population.

Objective: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers.

Design, Setting, And Participants: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected.

Main Outcomes And Measures: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview.

Results: Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P < .001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P < .001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P < .001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P < .001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P = .008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P = .001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P = .003) of being a BRCA2 PV carrier.

Conclusions And Relevance: Significant differences in the cancer spectrum were observed in male BRCA2, compared with BRCA1, PV carriers. These data may inform future recommendations for surveillance of BRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men with BRCA1/2 PVs.

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Source
http://dx.doi.org/10.1001/jamaoncol.2020.2134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333177PMC
August 2020

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