Genetic Testing and Results in a Population-Based Cohort of Breast Cancer Patients and Ovarian Cancer Patients

PURPOSE Genetic testing for cancer risk has expanded rapidly. We examined clinical genetic testing and results among population-based patients with breast and ovarian cancer. METHODS The study included all women 20 years of age or older diagnosed with breast or ovarian cancer in California and Georgia between 2013 and 2014 and reported to the SEER registries covering the entire state populations. SEER data were linked to results from four laboratories that performed nearly all germline cancer genetic testing. Testing use and results were analyzed at the gene level. RESULTS There were 77,085 patients with breast cancer and 6,001 with ovarian cancer. Nearly one quarter of those with breast cancer (24.1%) and one third of those with ovarian cancer (30.9%) had genetic test results. Among patients with ovarian cancer, testing was lower in blacks (21.6%; 95% CI, 18.1% to 25.4%; v whites, 33.8%; 95% CI, 32.3% to 35.3%) and uninsured patients (20.8%; 95% CI, 15.5% to 26.9%; v insured patients, 35.3%; 95% CI, 33.8% to 36.9%). Prevalent pathogenic variants in patients with breast cancer were BRCA1 (3.2%), BRCA2 (3.1%), CHEK 2 (1.6%), PALB2 (1.0%), ATM (0.7%), and NBN (0.4%); in patients with ovarian cancer, prevalent pathogenic variants were BRCA1 (8.7%), BRCA2 (5.8%), CHEK2 (1.4%), BRIP1 (0.9%), MSH2 (0.8%), and ATM (0.6%). Racial/ethnic differences in pathogenic variants included BRCA1 (ovarian cancer: whites, 7.2%; 95% CI, 5.9% to 8.8%; v Hispanics, 16.1%; 95% CI, 11.8% to 21.2%) and CHEK2 (breast cancer: whites, 2.3%; 95% CI, 1.8% to 2.8%; v blacks, 0.1%; 95% CI, 0% to 0.8%). When tested for all genes that current guidelines designate as associated with their cancer type, 7.8% of patients with breast cancer and 14.5% of patients with ovarian cancer had pathogenic variants. CONCLUSION Clinically-tested patients with breast and ovarian cancer in two large, diverse states had 8% to 15% prevalence of actionable pathogenic variants. Substantial testing gaps and disparities among patients with ovarian cancer are targets for improvement.

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Genetic testing and results in population-based breast cancer patients and ovarian cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.1578 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. 1578-1578

Author(s):

Allison W. Kurian ◽

Kevin C. Ward ◽

Nadia Howlader ◽

Dennis Deapen ◽

Ann S. Hamilton ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Patients ◽

Population Based ◽

Breast Cancer Patients

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Abstract PS8-14: Pathogenic variants in hereditary cancer syndrome genes are prevalent among breast cancer patients not meeting various ex-U.S. genetic testing guidelines

10.1158/1538-7445.sabcs20-ps8-14 ◽

2021 ◽

Author(s):

Sarah M Nielsen ◽

Peter Beitsch ◽

Pat Whitworth ◽

Emily Decker ◽

Natalie Rickers ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Cancer Patients ◽

Hereditary Cancer ◽

Hereditary Cancer Syndrome ◽

Breast Cancer Patients ◽

Cancer Syndrome ◽

Pathogenic Variants ◽

Genetic Testing Guidelines

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Disparities in pretest genetic counseling among a population-based sample of young breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.1579 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 1579-1579

Author(s):

Sonya Reid-Lawrence ◽

Tuya Pal ◽

Ingrid A. Mayer ◽

Xiao-Ou Shu ◽

Ann Tezak ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Counseling ◽

Genetic Testing ◽

Cancer Patients ◽

Hereditary Cancer ◽

Medical Records ◽

Population Based ◽

Racial Groups ◽

Breast Cancer Patients ◽

Young Breast Cancer

1579 Background: Per national practice guidelines, pre-test genetic counseling (GC) through a board-certified or credentialed genetics health professional (GHP) is recommended when testing for hereditary cancer. We sought to compare differences in rates of pre-test GC among young breast cancer (BC) patients tested with or without GHP involvement across three racial groups (Black, Hispanic and non-Hispanic white (NHW)). Methods: A population-based sample of Black, Hispanic and NHW women diagnosed with invasive BC ≤ age 50 from 2009 to 2012 were recruited through the Florida State Cancer Registry. Participants were asked to complete a baseline questionnaire and release medical records for verification of clinical information and genetic testing. We compared the rates of pre-test GC across racial groups in women tested with or without GHP involvement using Analysis of Variance. Multivariate logistic regression analysis was also conducted to adjust for potential confounders. Results: Of 1618 participants, 828 had genetic testing based on medical records and/or self-reported on their questionnaire. There were 170 (20.5%) with GHP involvement (either through consultation and/or test ordering) and the remaining 658 women (79.5%) had no documentation of GHP involvement. Among patients tested without GHP involvement, rates of pre-test GC were significantly lower among Black women (34.8%) compared to Hispanics (80%) and NHW (78.7%) (p < 0.001). In contrast, among those with GHP involvement, rates of pre-test GC were similar among Black (89.7%), Hispanic (81.1%) and NHW (84.6%) (p = 0.89). Conclusions: Our results suggest that among young breast cancer patients tested for hereditary cancer without GHP involvement, Blacks were significantly less likely to receive pre-test GC, compared to the other two groups. In contrast, rates of pre-test GC among those with GHP involvement were similar across all groups. These results suggest a disparity in receipt of pre-test GC (which is standard of care per national guidelines) among Blacks tested without GHP involvement. These findings are concerning given the need to offer guideline-adherent care to all patients receiving hereditary cancer testing.

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Trends in germline genetic testing and results into survivorship for women diagnosed with breast cancer or ovarian cancer, 2013 to 2017.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.29_suppl.273 ◽

2020 ◽

Vol 38 (29_suppl) ◽

pp. 273-273

Author(s):

Steven J. Katz ◽

Monica Morrow ◽

Allison W. Kurian

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Patients ◽

Ethnic Minorities ◽

Test Results ◽

Breast Cancer Patients ◽

Level Of Evidence ◽

Number Of Genes ◽

Racial Ethnic

273 Background: Genetic testing is increasingly central to breast and ovarian cancer prevention and treatment. Yet, little is known about trends and disparities in receipt of testing and test results after diagnosis. Methods: We linked all female patients with breast or ovarian cancer diagnosed from 2013-2017 in Georgia and California and reported to SEER registries to genetic testing results from four laboratories (Ambry Genetics, GeneDx, Invitae, Myriad Genetics). We combined test results from all labs with SEER data. We classified a test as a multigene panel (MGP) if it included other genes in addition to BRCA1/2. We grouped pathogenic variants (PVs) by level of evidence that supported clinical testing: BRCA1/2; other genes associated with well-established syndromes (syndromic genes); genes whose cancer association is less certain (emerging genes); and any other tested genes (other genes). We categorized patients with a variant of unknown significance (VUS) in any gene but no PVs as VUS-only. We examined trends in receipt of testing and test results overall and by race/ethnic groups. Results: One quarter (25.5%) of 198,001 breast cancer patients, and 34.5% of 15,461 ovarian cancer patients had genetic tests. Test rates increased by only 2% annually; while the number of genes tested per patient increased by 28%. The mean number of genes tested rose from 10 to 35 during the study period. In early 2013, 18.3% of testers had a PV or VUS result, which increased to 37.2% in late 2017. The upward trend was largely due to increase in VUS-only findings. The proportion of tested breast cancer patients with any PV increased from 9.1% to 9.9%: PVs in BRCA1/2 decreased from 7.5% to 5.0% (p<.001), while PV yield for the two other clinical categories (syndromic and emerging genes) increased from 1.6% to 4.9% (p<.001). PVs in any of the other 61 genes were very rare (<1%). By contrast, the VUS rate in breast cancer patients increased markedly from 9.6% in 2013 to 26.2% in 2017. The VUS rate was higher in racial/ethnic minorities (41.0% Asian, 36.5%% Black, 28.0% Latinas versus 25.6% non-Hispanic Whites diagnosed in 2017; p<.001). We observed similar findings for patients with ovarian cancer. Conclusions: A large gap persists in testing ovarian cancer patients (35% versus 100% recommended). Testing more genes per patient was associated with a substantial racial/ethnic gap in VUS with little difference in yield on clinically relevant PVs. Testing a limited subset of genes may optimize yield-to-noise of genetic testing, particularly for racial/ethnic minorities.

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Analysis of clinical characteristics in breast cancer patients with the Japanese founder mutation of BRCA1 L63X.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.22 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 22-22

Author(s):

Reiko Yoshida ◽

Mayuko Inuzuka ◽

Tomoko Watanabe ◽

Junko Yotsumoto ◽

Takashi Kuwayama ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Clinical Characteristics ◽

Founder Mutation ◽

Breast Cancers ◽

Pathological Features ◽

Breast Cancer Patients ◽

Breast And Ovarian Cancer ◽

Brca1 Mutations

22 Background: Hereditary breast and ovarian cancer (HBOC) is a high-penetrance inherited disease, and founder mutation has been reported in the West. However, there are yet no reports of founder mutation of HBOC on breast cancer in the Japanese population. In this study, we report the breast cancer clinical characteristics of L63X, which is one of the founder mutations in BRCA1 in the Japanese population. Methods: Data on 223 affected breast cancer patients (28 BRCA1 carriers, 19 BRCA2 carriers, and 176 non-carriers) were collected at Showa University in Tokyo from September 2010 to June 2015. In 22 independent mutations of BRCA1, the L63X mutation was detected in 9 patients. Data regarding the age of breast cancer onset, pathological features, clinical features, and family history were collected. Results: The age of onset was no significant differences between the L63X mutation and other BRCA1 mutations (39.7 vs. 38.5years). The proportion of triple negative breast cancer patients was 87.5% in the L63X mutation carriers and 89.5% in other BRCA1 mutation carriers. No patients of the L63X affected bilateral breast cancers. On the other hand, 36.7% of other BRCA1mutations affected bilateral breast cancers. There was no significant difference in pathological features (intrinsic subtype, nuclear grade and ki-67 index). The L63X carriers tended to have a family history of breast cancers. All L63X mutations were detected in the Eastern part of Japan. Conclusions: The breast cancer clinical characteristics of L63X might be considered no different from other types of BRCA1 mutations. Recently, it has been reported that breast and ovarian cancer risks varied according to the type and location of BRCA1/2 mutations. L63X mutation is located in the breast cancer cluster region in BRCA1. Further investigation is necessary for appropriate validation and accumulation of data.

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Non-BRCA1/2 Variants Detected in a High-Risk Chilean Cohort With a History of Breast and/or Ovarian Cancer

Journal of Global Oncology ◽

10.1200/jgo.18.00163 ◽

2019 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Christina Adaniel ◽

Francisca Salinas ◽

Juan Manuel Donaire ◽

Maria Eugenia Bravo ◽

Octavio Peralta ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

High Risk ◽

Genetic Predisposition ◽

Cancer Syndrome ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

Cancer Program ◽

Genetic Test Results

PURPOSE Little is known about the genetic predisposition to breast and ovarian cancer among the Chilean population, in particular genetic predisposition beyond BRCA1 and BRCA2 mutations. In the current study, we aim to describe the germline variants detected in individuals who were referred to a hereditary cancer program in Santiago, Chile. METHODS Data were retrospectively collected from the registry of the High-Risk Breast and Ovarian Cancer Program at Clínica Las Condes, Santiago, Chile. Data captured included index case diagnosis, ancestry, family history, and genetic test results. RESULTS Three hundred fifteen individuals underwent genetic testing during the study period. The frequency of germline pathogenic and likely pathogenic variants in a breast or ovarian cancer predisposition gene was 20.3%. Of those patients who underwent testing with a panel of both high- and moderate-penetrance genes, 10.5% were found to have pathogenic or likely pathogenic variants in non- BRCA1/2 genes. CONCLUSION Testing for non- BRCA1 and -2 mutations may be clinically relevant for individuals who are suspected to have a hereditary breast or ovarian cancer syndrome in Chile. Comprehensive genetic testing of individuals who are at high risk is necessary to further characterize the genetic susceptibility to cancer in Chile.

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Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

Tumor Biology ◽

10.1177/1010428317694303 ◽

2017 ◽

Vol 39 (2) ◽

pp. 101042831769430 ◽

Cited By ~ 3

Author(s):

Mina Darooei ◽

Subhadra Poornima ◽

Bibi Umae Salma ◽

Gayatri R Iyer ◽

Akhilesh N Pujar ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Cancer Patients ◽

Pedigree Analysis ◽

Care Hospital ◽

Breast Cancer Patients ◽

Cancer Syndrome ◽

Breast And Ovarian Cancer ◽

Targeted Mutation

Global burden of breast cancer is expected to increase to >2 million new cases every year by 2030 and 10% of these are likely to have hereditary breast and ovarian cancer syndrome. Identifying these individuals by pedigree and BRCA1/2 mutation analyses will enable us to offer targeted mutation testing and appropriate counseling. This study from a tertiary care hospital showed that of the 127 breast cancer patients on treatment during 2014–2015, 24 of them fulfilled the criteria of hereditary breast and ovarian cancer syndrome after detailed verbal autopsy and pedigree analysis, and BRCA1 and 2 next-generation sequencing done after pre-test counseling revealed mutations in 13 cases (54%), these included 9 BRCA1 mutations (69%) and 4 BRCA2 mutation (31%). Subsequent post-test counseling recommended targeted mutation analysis for 64 high-risk members in these 13 families with pathogenic mutations, which will help in surveillance for early detection, appropriate management, and prevention of the disease by decreasing the burden to both family and nation. Results from this preliminary study highlight the importance of genetic counseling, pedigree analysis, and genetic testing. It can be recommended that all oncology units should have a genetic counseling service for providing appropriate support to oncologists, patients, and families to prevent unnecessary testing; however, breast cancer screening program is incomplete without evaluating for hereditary breast and ovarian cancer syndrome.

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Study of the Genetic Variants in BRCA1/2 and Non-BRCA Genes in a Population-Based Cohort of 2155 Breast/Ovary Cancer Patients, Including 443 Triple-Negative Breast Cancer Patients, in Argentina

Cancers ◽

10.3390/cancers13112711 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2711

Author(s):

Angela R. Solano ◽

Pablo G. Mele ◽

Fernanda S. Jalil ◽

Natalia C. Liria ◽

Ernesto J. Podesta ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Population Based ◽

Breast Cancer Patients ◽

Ovary Cancer ◽

Brca Gene ◽

Pathogenic Variants ◽

Brca Genes

Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. We aim to report a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC), in our population. In total 2155 BOC patients (1900 analyzed in BRCA1/2 and 255 by multigenic panels) gave 372 (17.2.6%) and 107 (24.1%) likely pathogenic/pathogenic variants (LPVs/PVs), including BRCA and non-BRCA genes, for the total and TNBC patients, respectively. When BOC was present in the same proband, a 51.3% rate was found for LPVs/PVs in BRCA1/2. Most of the LPVs/PVs in the panels were in BRCA1/2; non-BRCA gene LPVs/PVs were in CDH1, CHEK2, CDKN2A, MUTYH, NBN, RAD51D, and TP53. TNBC is associated with BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent PVs in BRCA1/2 genes (mostly in BRCA1) do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated.

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