Inadequate Family History Assessment by Oncologists is an Important Physician Barrier to Referral for Hereditary Breast Cancer Evaluation

Purpose: In this brief report, we ask whether women’s interpretation of breast cancer risk based on their low likelihood of carrying a BRCA1/2 mutation is associated with their information-sharing behavior, and whether misinterpretation is associated with motives for sharing the result. Methods: Women in mammography clinics who completed a brief family history assessment and deemed to be at low likelihood of carrying a BRCA1/2 mutation were asked to complete a 1-time online survey between June 2016 and January 2017. Results: One-third (44/148) of women shared their family history screen result with someone in their social network. Result information was shared largely with a first-degree female relative to express feelings of relief (77%, 33/43). There were no differences in likelihood of sharing based on breast cancer risk interpretation. However, women who misinterpreted the implications of the result for general breast cancer risk reported more motives to share the result with their social network than those who accurately interpreted their breast cancer risk. Conclusions: As family history-based screening for hereditary breast cancer is broadly implemented, the communication needs of the majority of women who will be unlikely of carrying a BRCA1/2 mutation must be considered. The motives of women who misinterpreted the implications of this result for breast cancer risk suggest the possibility that miscommunication could be spread to the broader family network.

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Race and family history assessment for breast cancer

Journal of General Internal Medicine ◽

10.1111/j.1525-1497.2004.40112.x ◽

2005 ◽

Vol 20 (1) ◽

pp. 75-80 ◽

Cited By ~ 19

Author(s):

Harvey J. Murff ◽

Daniel Byrne ◽

Jennifer S. Haas ◽

Ann Louise Puopolo ◽

Troyen A. Brennan

Keyword(s):

Breast Cancer ◽

Family History ◽

Family History Assessment

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Germline mutations in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

10.1101/2020.08.09.20171165 ◽

2020 ◽

Author(s):

Megan Ren ◽

Anali Orozco ◽

Kang Shao ◽

Boyang Cao ◽

Lusheng Wang ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Hereditary Breast Cancer ◽

Breast Cancer Mortality ◽

Age At Diagnosis ◽

Early Age ◽

Cancer Genes ◽

Pathogenic Variants ◽

Cancer Susceptibility Genes ◽

Breast Cancer Genes

Background: Mutations in hereditary breast cancer genes play an important role in the risk for cancer, however, little is known of the type and frequency of mutations in Central American populations, including Guatemala. Methods: Two separate panels of known cancer susceptibility genes were used to sequence blood DNA from 664 unselected breast cancer cases from two large hospitals in Guatemala. Variants were annotated with ClinVar and VarSome. Data from a structured questionnaire was used to compare mutation carriers of medium and high penetrance genes. Results: A total of 73 out of 664 subjects (11%) had a variant classified as pathogenic in a gene with known high or medium penetrance for inherited breast cancer. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%) and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6, and rare pathogenic variants detected in the low penetrance genes AXIN2, FH, MLH1, MSH2, MUTYH, NF1, and SDHB. The high ratio of BRCA1/BRCA2 mutations is due to the presence of two potential founder mutations, BRCA1 c.212+1G>A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Compared to all others, cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P<0.001), more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P=0.038) or breast cancer (33% vs 15%, P<0.001). Mammography usage was less frequent in lower SES women indicating this group is less likely to be screened for breast cancer (p < 0.001). Conclusions: Guatemalan women have rates of hereditary breast cancer mutations similar to other populations, and these women are more likely to have early age at diagnosis and family history. This data supports the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

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Hereditary Breast-Ovarian Cancer at the Bedside: Role of the Medical Oncologist

Journal of Clinical Oncology ◽

10.1200/jco.2003.05.096 ◽

2003 ◽

Vol 21 (4) ◽

pp. 740-753 ◽

Cited By ~ 39

Author(s):

Henry T. Lynch ◽

Carrie L. Snyder ◽

Jane F. Lynch ◽

Bronson D. Riley ◽

Wendy S. Rubinstein

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Family History ◽

High Risk ◽

Hereditary Breast Cancer ◽

Present Report ◽

Brca1 And Brca2 ◽

Cancer Family ◽

Hereditary Breast Ovarian Cancer

Purpose: To provide practical considerations for diagnosing, counseling, and managing patients at high risk for hereditary breast cancer. Design: We have studied 98 extended hereditary breast cancer (HBC)/hereditary breast-ovarian cancer (HBOC) families with BRCA1/2 germline mutations. From these families, 1,315 individuals were counseled and sampled for DNA testing. Herein, 716 of these individuals received their DNA test results in concert with genetic counseling. Several challenging pedigrees were selected from Creighton University’s hereditary cancer family registry, as well as one family from Evanston/Northwestern Healthcare, to be discussed in this present report. Results: Many obstacles were identified in diagnosis, counseling, and managing patients at high risk for HBC/HBOC. These obstacles were early noncancer death of key relatives, perception of insurance or employment discrimination, fear, anxiety, apprehension, reduced gene penetrance, and poor compliance. Other important issues such as physician culpability and malpractice implications for failure to collect or act on the cancer family history were identified. Conclusion: When clinical gene testing emerged for BRCA1 and BRCA2, little was known about the efficacy of medical interventions. Potential barriers to uptake of testing were largely unexplored. Identification and referral of high-risk patients and families to genetic counseling can greatly enhance the care of the population at the highest risk for cancer. However, because premonitory physical stigmata are absent in most of these syndromes, an HBOC diagnosis may be missed unless a careful family history of cancer of the breast, ovary, or several integrally associated cancers is obtained.

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Panel Testing for Familial Breast Cancer: Calibrating the Tension Between Research and Clinical Care

Journal of Clinical Oncology ◽

10.1200/jco.2015.63.7454 ◽

2016 ◽

Vol 34 (13) ◽

pp. 1455-1459 ◽

Cited By ~ 107

Author(s):

Ella R. Thompson ◽

Simone M. Rowley ◽

Na Li ◽

Simone McInerny ◽

Lisa Devereux ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Hereditary Breast Cancer ◽

Familial Cancer ◽

Clinical Care ◽

Loss Of Function ◽

Brca1 And Brca2 ◽

Similar Frequency ◽

New Genes ◽

Population Controls

Purpose Gene panel sequencing is revolutionizing germline risk assessment for hereditary breast cancer. Despite scant evidence supporting the role of many of these genes in breast cancer predisposition, results are often reported to families as the definitive explanation for their family history. We assessed the frequency of mutations in 18 genes included in hereditary breast cancer panels among index cases from families with breast cancer and matched population controls. Patients and Methods Cases (n = 2,000) were predominantly breast cancer-affected women referred to specialized Familial Cancer Centers on the basis of a strong family history of breast cancer and BRCA1 and BRCA2 wild type. Controls (n = 1,997) were cancer-free women from the LifePool study. Sequencing data were filtered for known pathogenic or novel loss-of-function mutations. Results Excluding 19 mutations identified in BRCA1 and BRCA2 among the cases and controls, a total of 78 cases (3.9%) and 33 controls (1.6%) were found to carry potentially actionable mutations. A significant excess of mutations was only observed for PALB2 (26 cases, four controls) and TP53 (five cases, zero controls), whereas no mutations were identified in STK11. Among the remaining genes, loss-of-function mutations were rare, with similar frequency between cases and controls. Conclusion The frequency of mutations in most breast cancer panel genes among individuals selected for possible hereditary breast cancer is low and, in many cases, similar or even lower than that observed among cancer-free population controls. Although multigene panels can significantly aid in cancer risk management and expedite clinical translation of new genes, they equally have the potential to provide clinical misinformation and harm at the individual level if the data are not interpreted cautiously.

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Correction to: Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06373-7 ◽

2021 ◽

Author(s):

Megan Ren ◽

Anali Orozco ◽

Kang Shao ◽

Anaseidy Albanez ◽

Jeremy Ortiz ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Hereditary Breast Cancer ◽

Age At Diagnosis ◽

Early Age ◽

Cancer Genes ◽

Germline Variants ◽

Breast Cancer Genes

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Germline mutations in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

10.21203/rs.3.rs-58163/v1 ◽

2020 ◽

Author(s):

Megan Ren ◽

Anali Orozco ◽

Kang Shao ◽

Anaseidy Albanez ◽

Jeremy Ortiz ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Hereditary Breast Cancer ◽

Breast Cancer Mortality ◽

Age At Diagnosis ◽

Early Age ◽

Cancer Genes ◽

Pathogenic Variants ◽

Cancer Susceptibility Genes ◽

Breast Cancer Genes

Abstract Background: Mutations in hereditary breast cancer genes play an important role in the risk for cancer, however, little is known of the type and frequency of mutations in Central American populations, including Guatemala.Methods: Two separate panels of known cancer susceptibility genes were used to sequence blood DNA from 664 unselected breast cancer cases from two large hospitals in Guatemala. Variants were annotated with ClinVar and VarSome. Data from a structured questionnaire was used to compare mutation carriers of medium and high penetrance genes.Results: A total of 73 out of 664 subjects (11%) had a variant classified as pathogenic in a gene with known high or medium penetrance for inherited breast cancer. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%) and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6, and rare pathogenic variants detected in the low penetrance genes AXIN2, FH, MLH1, MSH2, MUTYH, NF1, and SDHB. The high ratio of BRCA1/BRCA2 mutations is due to the presence of two potential founder mutations, BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Compared to all others, cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). Mammography usage was less frequent in lower SES women indicating this group is less likely to be screened for breast cancer (p < 0.001).Conclusions: Guatemalan women have rates of hereditary breast cancer mutations similar to other populations, and these women are more likely to have early age at diagnosis and family history. This data supports the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

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Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06305-5 ◽

2021 ◽

Author(s):

Megan Ren ◽

Anali Orozco ◽

Kang Shao ◽

Anaseidy Albanez ◽

Jeremy Ortiz ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Hereditary Breast Cancer ◽

Cancer Susceptibility ◽

Breast Cancer Mortality ◽

Age At Diagnosis ◽

Early Age ◽

Cancer Genes ◽

Cancer Susceptibility Genes ◽

Breast Cancer Genes

Abstract Purpose Mutations in hereditary breast cancer genes play an important role in the risk for cancer. Methods Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. Results A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). Conclusions Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

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Ethnic aspects of hereditary breast cancer

Siberian Journal of Oncology ◽

10.21294/1814-4861-2019-18-2-102-108 ◽

2019 ◽

Vol 18 (2) ◽

pp. 102-108

Author(s):

P. A. Gervas ◽

A. Yu. Molokov ◽

E. V. Panpherova ◽

L. Ph. Pisareva ◽

N. V. Cherdyntseva

Keyword(s):

Breast Cancer ◽

Family History ◽

Ethnic Groups ◽

Russian Federation ◽

Hereditary Breast Cancer ◽

Indigenous Population ◽

Brca1 Gene ◽

Molecular Therapy ◽

Brca1 And Brca2 ◽

The Russian Federation

This studyaimed to reveal the spectrum of BRca1 and BRca2 genes mutation in various ethnic groups of the Russian Federation. asystematic literature search includes data for the past 10 years and was conducted by using electronic databases of pubmed, eliBRaRY and ect.Material and methods.The review includes research data on the frequency of mutations of breast cancer-associated genes in various ethnic groups of the Russian Federation.Results.For «slavic» patients with a family history, the BRca1/2 mutation testing is the standard of care. in addition, the development of new antitumour drugs has resulted in improved survival rates. more than 1000 mutations of the BRca1 gene have been identified. Recent research is focused on the confirmation the beneficial effect of identified mutations. For the indigenous population (mongoloid ethnic groups), there are no standards for the treatment of inherited breast cancer. thus, the advances in molecular oncology for the treatment of hereditary breast cancer are not available for the indigenous population of the Russian Federation.Conclusion.In this context, the search for markers of early cancer detection and the development of criteria for therapy response are relevant for indigenous people. the development of new predictive and prognostic criteria of breast cancer among mongoloid ethnic groups with a family history will allow the innovative strategies for personalized molecular therapy to be developed.

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