Malignant Abnormalities in Male <i>BRCA</i> Mutation Carriers

Tamir, Shlomit; Kedar, Inbal; Benjaminov, Ofer; Baniel, Jack; Tabachnik, Tzlil; Margel, David

doi:10.1001/jamaoncol.2018.0271

Cited by 22 publications

(30 citation statements)

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“…The finding that only breast/ovarian counseling rates are disparate in men may suggest instead a failure of identifying and referring men at risk for HBOC, or a perceived lack of relevance for counseling in men for HBOC. It is important to note that men with BRCA1/2 pathogenic variants, for example, are not only at risk for male breast cancer, but also melanoma, pancreatic, and prostate cancers . Furthermore, male BRCA carriers who develop cancer are diagnosed with higher grade and later stage disease for both breast and prostate cancers .…”

Section: Discussionmentioning

confidence: 99%

“…It is important to note that men with BRCA1/2 pathogenic variants, for example, are not only at risk for male breast cancer, but also melanoma, pancreatic, and prostate cancers . Furthermore, male BRCA carriers who develop cancer are diagnosed with higher grade and later stage disease for both breast and prostate cancers . Recent studies on men with prostate cancer have noted that men with BRCA2 pathogenic variants have a higher mortality compared to their BRCA2 ‐negative counterparts .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, male BRCA carriers who develop cancer are diagnosed with higher grade and later stage disease for both breast and prostate cancers . Recent studies on men with prostate cancer have noted that men with BRCA2 pathogenic variants have a higher mortality compared to their BRCA2 ‐negative counterparts . Lastly, identifying male carriers is invaluable to inform risk assessment for future generations (daughters and sons).…”

Section: Discussionmentioning

confidence: 99%

“…Future research should move beyond the sociodemographic distribution of those obtaining genetic counseling to focus on overall access to and availability of genetic counseling services. As current data suggest low counseling and testing rates, assessing what barriers to testing exist via genetic counseling, as well as mechanisms to improve genetic testing rates through genetic counseling, are imperative . Further, given the emerging importance of additional cancer types, such as prostate and pancreatic, as indications of hereditary cancer syndromes, a more robust survey design is needed to include these specifically among possible reasons for genetic counseling.…”

Section: Discussionmentioning

confidence: 99%

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Painting a portrait: Analysis of national health survey data for cancer genetic counseling

Stamp¹,

Gordon

Childers

et al. 2019

Cancer Medicine

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Background Despite a growing body of literature describing the geographic and sociodemographic distribution of cancer genetic testing, work focused on these domains in cancer genetic counseling is limited. Research describing the epidemiology of cancer genetic counseling has mainly focused on isolated populations, a single gender (women) and a single condition (hereditary breast and ovarian cancer). Study findings to date are contradictory, making it unclear what, if any, disparities in receipt of cancer genetic counseling exist. Methods Utilizing the 2015 National Health Interview Survey (NHIS)—a cross‐sectional, in person interview survey collecting self‐reported health data for the US population—geographic and sociodemographic factors were compared between those receiving genetic counseling and the national sample. Bivariate analysis and subsequent multivariable logistic regression were performed with stratification by cancer status (affected/unaffected). Reason for (eg, doctor recommended) and focus of (eg, breast/ovarian) genetic counseling were also assessed. To generate nationally representative estimates, all analyses were adjusted for survey weights. Results An estimated 4.8 million individuals in the United States had cancer genetic counseling. On bivariate analysis, there were significant differences in proportions undergoing genetic counseling by sex, race/ethnicity, insurance, citizenship, education, age, and cancer status (P < 0.01). After adjustment, however, only female sex (Odds Ratio [OR]: 1.78 [95% CI: 1.18‐2.67]) remained a significant predictor of genetic counseling among the affected. Among the unaffected, female sex (OR: 1.70 [1.30‐2.21]), non‐Hispanic black race (OR: 1.44 [1.02‐2.05], reference: non‐Hispanic white), graduate education (OR: 1.76 [1.03‐2.98], reference: less than high school), and age (OR: 1.06 [1.01‐1.11]) predicted higher rates of genetic counseling. An estimated 2.1 million individuals have undergone genetic counseling focused on breast/ovarian cancer, 1.3 million on colorectal cancer, and 1.4 million on “other” cancers. Of those receiving genetic counseling focused on breast/ovarian cancer, 3% were male and 97% female (breast cancer alone‐4% male, 96% female); for colorectal cancer, 49% male and 51% female, and for “other” cancers, 60% male and 40% female. The majority of individuals receiving genetic counseling reported they did so because their doctor recommended it (66%), with smaller proportions describing self (12%), family (10%), or media (5%) influences as the primary reason. Conclusion This is the first study to depict the sociodemographic and geographic distribution of cancer genetic counseling at the national level. Despite perceived disparities in access, cancer genetic counseling in the United States appears to be accessed by individuals of diverse racial/ethnic backgrounds, with various insurance coverage and educational levels, and across a broad range of ages and geographic regions. The only sociodemographic factor that independently predicted rec...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Painting a portrait: Analysis of national health survey data for cancer genetic counseling

Stamp¹,

Gordon

Childers

et al. 2019

Cancer Medicine

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“…Men carrying mutations in BRCA1/2 have been reported to develop melanomas [6] or pancreatic [7], prostatic [9], and breast cancers [10]. Moreover, much clinical evidence [11][12][13][14][15] indicates that the germline or somatic inactivation of BRCA1/2 in male patients with malignancy confers sensitivity to DNA damaging therapies, such as poly ADP-ribose polymerase inhibitor (PARPi) [16,17].…”

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confidence: 99%

Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

Sun

Chao

et al. 2020

Preprint

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Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications.Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n=349), as well as in male patients without BRCAm (n=4577).Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8% and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males.Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.

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Characterization of the Cancer Spectrum in Men With GermlineBRCA1andBRCA2Pathogenic Variants

Silvestri¹,

Leslie²,

Barnes³

et al. 2020

JAMA Oncol

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and the CIMBA Group 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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Malignant Abnormalities in Male BRCA Mutation Carriers

Abstract: Author Contributions: Drs Fallon and Laird had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Cited by 22 publications

References 6 publications

Painting a portrait: Analysis of national health survey data for cancer genetic counseling

Painting a portrait: Analysis of national health survey data for cancer genetic counseling

Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

Characterization of the Cancer Spectrum in Men With GermlineBRCA1andBRCA2Pathogenic Variants

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