TY - JOUR

T1 - Characterization of the Cancer Spectrum in Men with Germline BRCA1 and BRCA2 Pathogenic Variants

T2 - Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

AU - Silvestri, Valentina

AU - Leslie, Goska

AU - Barnes, Daniel R.

AU - Agnarsson, Bjarni A.

AU - Aittomäki, Kristiina

AU - Alducci, Elisa

AU - Andrulis, Irene L.

AU - Barkardottir, Rosa B.

AU - Barroso, Alicia

AU - Barrowdale, Daniel

AU - Benitez, Javier

AU - Bonanni, Bernardo

AU - Borg, Ake

AU - Buys, Saundra S.

AU - Caldés, Trinidad

AU - Caligo, Maria A.

AU - Capalbo, Carlo

AU - Campbell, Ian

AU - Chung, Wendy K.

AU - Claes, Kathleen B.M.

AU - Colonna, Sarah V.

AU - Cortesi, Laura

AU - Couch, Fergus J.

AU - De La Hoya, Miguel

AU - Diez, Orland

AU - Ding, Yuan Chun

AU - Domchek, Susan

AU - Easton, Douglas F.

AU - Ejlertsen, Bent

AU - Engel, Christoph

AU - Evans, D. Gareth

AU - Feliubadalò, Lidia

AU - Foretova, Lenka

AU - Fostira, Florentia

AU - Géczi, Lajos

AU - Gerdes, Anne Marie

AU - Glendon, Gord

AU - Godwin, Andrew K.

AU - Goldgar, David E.

AU - Hahnen, Eric

AU - Hogervorst, Frans B.L.

AU - Hopper, John L.

AU - Hulick, Peter J.

AU - Isaacs, Claudine

AU - Izquierdo, Angel

AU - James, Paul A.

AU - Janavicius, Ramunas

AU - Jensen, Uffe Birk

AU - John, Esther M.

AU - Joseph, Vijai

AU - Konstantopoulou, Irene

AU - Kurian, Allison W.

AU - Kwong, Ava

AU - Landucci, Elisabetta

AU - Lesueur, Fabienne

AU - Loud, Jennifer T.

AU - Machackova, Eva

AU - Mai, Phuong L.

AU - Majidzadeh-A, Keivan

AU - Manoukian, Siranoush

AU - Montagna, Marco

AU - Moserle, Lidia

AU - Mulligan, Anna Marie

AU - Nathanson, Katherine L.

AU - Nevanlinna, Heli

AU - Ngeow Yuen Ye, Joanne

AU - Nikitina-Zake, Liene

AU - Offit, Kenneth

AU - Olah, Edith

AU - Olopade, Olufunmilayo I.

AU - Osorio, Ana

AU - Papi, Laura

AU - Park, Sue K.

AU - Pedersen, Inge Sokilde

AU - Perez-Segura, Pedro

AU - Petersen, Annabeth H.

AU - Pinto, Pedro

AU - Porfirio, Berardino

AU - Pujana, Miquel Angel

AU - Radice, Paolo

AU - Rantala, Johanna

AU - Rashid, Muhammad U.

AU - Rosenzweig, Barak

AU - Rossing, Maria

AU - Santamariña, Marta

AU - Schmutzler, Rita K.

AU - Senter, Leigha

AU - Simard, Jacques

AU - Singer, Christian F.

AU - Solano, Angela R.

AU - Southey, Melissa C.

AU - Steele, Linda

AU - Steinsnyder, Zoe

AU - Stoppa-Lyonnet, Dominique

AU - Tan, Yen Yen

AU - Teixeira, Manuel R.

AU - Teo, Soo H.

AU - Terry, Mary Beth

AU - Thomassen, Mads

AU - Toland, Amanda E.

AU - Torres-Esquius, Sara

AU - Tung, Nadine

AU - Van Asperen, Christi J.

AU - Vega, Ana

AU - Viel, Alessandra

AU - Vierstraete, Jeroen

AU - Wappenschmidt, Barbara

AU - Weitzel, Jeffrey N.

AU - Wieme, Greet

AU - Yoon, Sook Yee

AU - Zorn, Kristin K.

AU - Mcguffog, Lesley

AU - Parsons, Michael T.

AU - Hamann, Ute

AU - Greene, Mark H.

AU - Kirk, Judy A.

AU - Neuhausen, Susan L.

AU - Rebbeck, Timothy R.

AU - Tischkowitz, Marc

AU - Chenevix-Trench, Georgia

AU - Antoniou, Antonis C.

AU - Friedman, Eitan

AU - Ottini, Laura

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1001/jamaoncol.2020.2134

DO - 10.1001/jamaoncol.2020.2134

M3 - Journal article

C2 - 32614418

AN - SCOPUS:85088708548

VL - 6

SP - 1218

EP - 1230

JO - JAMA Oncology

JF - JAMA Oncology

SN - 2374-2437

IS - 8

ER -