Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019

2021 ◽  
pp. JCO.20.02785
Author(s):  
Allison W. Kurian ◽  
Kevin C. Ward ◽  
Paul Abrahamse ◽  
Irina Bondarenko ◽  
Ann S. Hamilton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Ovarian Cancer Risk ◽  
Test Results ◽  
Pathogenic Variants ◽  
Uncertain Significance ◽  
Hispanic White ◽  
Cancer Risk Reduction ◽  
Gene Category

PURPOSE Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use. METHODS SEER records of women of age ≥ 20 years diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia were linked to the results of clinical germline testing through 2019. We measured testing trends, rates of variants of uncertain significance (VUS), and pathogenic variants (PVs). RESULTS One quarter (25.2%) of 187,535 patients with breast cancer and one third (34.3%) of 14,689 patients with ovarian cancer were tested; annually, testing increased by 2%, whereas the number of genes tested increased by 28%. The prevalence of test results by gene category for breast cancer cases in 2017 were BRCA1/2 , PVs 5.2%, and VUS 0.8%; breast cancer–associated genes or ovarian cancer–associated genes ( ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53), PVs 3.7%, and VUS 12.0%; other actionable genes ( APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL) PVs 0.6%, and VUS 0.5%; and other genes, PVs 0.3%, and VUS 2.6%. For ovarian cancer cases in 2017, the prevalence of test results were BRCA1/2, PVs 11.0%, and VUS 0.9%; breast or ovarian genes, PVs 4.0%, and VUS 12.6%; other actionable genes, PVs 0.7%, and VUS 0.4%; and other genes, PVs 0.3%, and VUS 0.6%. VUS rates doubled over time (2013 diagnoses: 11.2%; 2017 diagnoses: 26.8%), particularly for racial or ethnic minorities (47.8% Asian and 46.0% Black, v 24.6% non-Hispanic White patients; P < .001). CONCLUSION A testing gap persists for patients with ovarian cancer (34.3% tested v nearly all recommended), whereas adding more genes widened a racial or ethnic gap in VUS results. Most PVs were in 20 breast cancer–associated genes or ovarian cancer–associated genes; testing other genes yielded mostly VUS. Quality improvement should focus on testing indicated patients rather than adding more genes.

scholarly journals Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

2019 ◽  
Vol 37 (6) ◽  
pp. 453-460 ◽  
Author(s):  
Peter D. Beitsch ◽  
Pat W. Whitworth ◽  
Kevin Hughes ◽  
Rakesh Patel ◽  
Barry Rosen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Germ Line ◽  
Test Results ◽  
Eligibility Criteria ◽  
Exact Test ◽  
Nccn Guidelines ◽  
Current Testing ◽  
Panel Testing ◽  
Pathogenic Variants

Purpose An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. Methods An institutional review board–approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act–compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. Results More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher’s exact test P = .4241). Conclusion Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

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

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.

Genetic assessment of hereditary breast and ovarian cancer in the Harris Health System: A five-year, single-center experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10587-10587
Author(s):  
Nicole Higashiyama ◽  
Shaun Bulsara ◽  
Susan G. Hilsenbeck ◽  
Tiffaney Tran ◽  
Ria Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Health System ◽  
Ashkenazi Jewish ◽  
Deleterious Mutations ◽  
Panel Testing ◽  
Risk Reducing ◽  
Racial Ethnic ◽  
Hispanic White

10587 Background: Identifying patients with hereditary breast cancer is critical since lifetime breast cancer risk is as high as 85% for those with germline BRCA1/2 mutations and preventive interventions can reduce that risk. However, genetic assessments and counseling are often underutilized among racial/ethnic minority populations. Reducing this genetic testing gap is important since hereditary breast/ovarian cancer syndromes occur among racial/ethnic minorities at least as frequently as non-Ashkenazi Jewish, non-Hispanic White populations. More information on variants in these populations is also needed to better define their genetic susceptibility. Methods: We conducted a retrospective study of adult patients evaluated for genetic testing for hereditary breast/ovarian cancer by a genetic counselor between October 1, 2009 and September 30, 2014 in Harris Health System which is a large, county health system composed mostly of underserved and minority patients. Data from 2015-2019 is currently being extracted and we are reporting the first 5 years of data. Descriptive statistics were used to summarize patient data. Results: 659 patients underwent genetic counseling (10.5% non-Hispanic White, 24.4% Black, 56.9% Hispanic, 5.9% Asian, and 2.3% other). Five patients had Ashkenazi Jewish ancestry. The majority of patients completed testing (87.4%) with 72.7% receiving financial assistance. Among those who did not complete testing, only 12.0% declined, while 66.3% did not meet guideline-based criteria or were recommended to have an affected relative tested. Multigene panel testing was not available until April 2014, so most underwent BRCA sequencing (75.0%) and/or a BRCA large rearrangement test (61.0%). 36.1% received multigene panel testing, 4.6% single site analysis, and 4.4% p53 sequencing. Deleterious mutations occurred in 98 (14.9%) patients: BRCA1 (n = 60), BRCA2 (n = 25), PALB2 (n = 7), ATM (n = 3), and other (n = 3). The distribution of races/ethnicities among those with deleterious mutations was similar to the overall population (7.1% non-Hispanic White, 18.4% Black, 69.4% Hispanic, 3.1% Asian, and 2.0% other). 80.6% of those with deleterious mutations had breast cancer. High rates of bilateral mastectomies were performed in patients with deleterious mutations: BRCA1 60%, BRCA2 55%, PALB2 57.1%, and ATM 33%. Risk-reducing salpingectomy or salpingo-oophorectomy was performed in 56.7% BRCA1, 60% BRCA2, 28.5% PALB2, and 33.3% other mutation carriers. Conclusions: We demonstrate that with the support of financial assistance programs, most patients who receive genetic counseling will accept genetic testing in a socioeconomically underserved, racially/ethnically diverse population. Identification of high-risk patients in these groups is critical since pathogenic variants in this population were common and more than half underwent risk-reducing procedures.

scholarly journals Risk reduction strategies for BRCA1/2 hereditary ovarian cancer syndromes: a clinical practice guideline

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Michelle Jacobson ◽  
Nadia Coakley ◽  
Marcus Bernardini ◽  
Kelly-Ann Branco ◽  
Laurie Elit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Risk Reduction ◽  
Hormone Replacement ◽  
Breast Cancer Mortality ◽  
Pathogenic Variant ◽  
Ovarian Cancer Risk ◽  
Eligibility Criteria ◽  
Cancer Risk Reduction

Abstract Objective The purpose of this guideline is to make recommendations regarding the care of women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2. Methods Draft recommendations were formulated based on evidence obtained through a systematic review of RCTs, comparative retrospective studies and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners. Results The literature search yielded 1 guideline, 5 systematic reviews, and 15 studies that met the eligibility criteria. Conclusions In women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2 screening for ovarian cancer is not recommended. Risk-reducing surgery is recommended to reduce the risk of ovarian cancer. In the absence of contraindications, premenopausal women undergoing RRSO should be offered hormone therapy until menopause. Systemic hormone replacement therapy, is not recommended for women who have had a personal history of breast cancer. RRSO should be considered for breast cancer risk reduction in women younger than 50 years. After a breast cancer diagnosis, RRSO for breast cancer mortality reduction can be considered within two years to women who harbour a pathogenic or likely pathogenic variant in BRCA1 if younger than the recommended age range for ovarian cancer risk reduction. RRSO before the age of 40 and specifically for breast cancer treatment in BRCA2 should be considered only if recommended by their breast cancer oncologist. Following RRSO, it is not recommended to do surveillance for peritoneal cancer.

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

2019 ◽  
Vol 37 (15) ◽  
pp. 1305-1315 ◽  
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 ◽  
Cancer Type ◽  
Breast Cancer Patients ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Variants ◽  
Genetic Test Results

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.

scholarly journals Racial and Ethnic Differences in Multigene Hereditary Cancer Panel Test Results for Women With Breast Cancer

2020 ◽  
Author(s):  
Siddhartha Yadav ◽  
Holly LaDuca ◽  
Eric C Polley ◽  
Chunling Hu ◽  
Nancy Niguidula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ethnic Differences ◽  
Race And Ethnicity ◽  
Test Results ◽  
Ashkenazi Jews ◽  
Case Control Studies ◽  
Racial And Ethnic Differences ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Hispanic White

Abstract To evaluate the racial and ethnic differences in prevalence of germline pathogenic variants (PVs) and the effect of race and ethnicity on breast cancer (BC) risk among carriers, results of multigene testing of 77 900 women with BC (non-Hispanic White [NHW] = 57 003; Ashkenazi-Jewish = 4798; Black = 6722; Hispanic = 5194; and Asian = 4183) were analyzed, and the frequency of PVs in each gene were compared between BC patients (cases) and race- and ethnicity-matched gnomAD reference controls. Compared with NHWs, BRCA1 PVs were enriched in Ashkenazi-Jews and Hispanics, whereas CHEK2 PVs were statistically significantly lower in Blacks, Hispanics, and Asians (all 2-sided P &lt; .05). In case-control studies, BARD1 PVs were associated with high risks (odds ratio &gt; 4.00) of BC in Blacks, Hispanics, and Asians; ATM PVs were associated with increased risk of BC among all races and ethnicities except Asians, whereas CHEK2 and BRIP1 PVs were associated with increased risk of BC among NHWs and Hispanics only. These findings suggest a need for personalized management of BC risk in PV carriers based on race and ethnicity.

Multi-center prospective analysis of risk-reducing salpingo-oophorectomy to prevent BRCA-associated breast and ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1003-1003 ◽  
Author(s):  
N. D. Kauff ◽  
S. M. Domchek ◽  
T. M. Friebel ◽  
J. B. Lee ◽  
R. Roth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Genetic Test ◽  
Ovarian Cancer Risk ◽  
Test Results ◽  
Breast And Ovarian Cancer ◽  
Genetic Test Results ◽  
Risk Reducing

1003 Background: Our groups previously reported on the efficacy of risk-reducing salpingo-oophorectomy (RRSO) for the prevention of BRCA-associated breast and ovarian cancer. (Kauff ND, et al. NEJM 2002; Rebbeck TR, et al. NEJM 2002) Limitations of those reports included relatively short prospective follow-up and lack of power to analyze the protection of RRSO when participants were stratified by BRCA1 vs. BRCA2. To address these limitations, we have pooled our updated datasets to provide robust estimates of the efficacy of RRSO. Methods: 886 women ≥ 30 years of age, with a deleterious mutation in BRCA1 or BRCA2 and ovaries in-situ at time of genetic test results, were enrolled on prospective follow-up studies at one of eleven centers from 11/1/1994 - 12/1/2004. Women chose to participate in either ovarian surveillance or undergo RRSO. Follow-up information was collected by questionnaire and medical record review. Follow-up time was counted from time of RRSO or from time of genetic test results for women who did not undergo RRSO. After excluding cancers diagnosed within the first 6 months of follow-up, the effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results: 559 (63%) participants underwent RRSO a median of 5 months after genetic test results. 12 occult ovarian or fallopian tube cancers were diagnosed at time of RRSO. During a mean 40 months follow-up, RRSO was associated with a 52% reduction in breast cancer risk and a 91% reduction in ovarian cancer risk (see Table ). When the cohort was stratified by mutation status, RRSO was associated with a reduced risk of BRCA1-associated ovarian cancer and BRCA2-associated breast cancer. Conclusions: The results confirm that RRSO is highly protective against BRCA-associated breast and ovarian cancer. These results also generate the hypothesis that the protection conferred by RRSO against specific cancers may differ between carriers of BRCA1 and BRCA2 mutations. [Table: see text] No significant financial relationships to disclose.

scholarly journals Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer

2019 ◽  
Vol 9 (1) ◽  
pp. 15 ◽  
Author(s):  
Ava Willoughby ◽  
Paul Andreassen ◽  
Amanda Toland
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Cancer Surveillance ◽  
Risk Scores ◽  
Breast And Ovarian Cancer ◽  
Cancer Susceptibility Genes ◽  
Uncertain Significance

Breast cancer screening modalities and guidelines continue to evolve and are increasingly based on risk factors, including genetic risk and a personal or family history of cancer. Here, we review genetic testing of high-penetrance hereditary breast and ovarian cancer genes, including BRCA1 and BRCA2, for the purpose of identifying high-risk individuals who would benefit from earlier screening and more sensitive methods such as magnetic resonance imaging. We also consider risk-based screening in the general population, including whether every woman should be genetically tested for high-risk genes and the potential use of polygenic risk scores. In addition to enabling early detection, the results of genetic screens of breast cancer susceptibility genes can be utilized to guide decision-making about when to elect prophylactic surgeries that reduce cancer risk and the choice of therapeutic options. Variants of uncertain significance, especially missense variants, are being identified during panel testing for hereditary breast and ovarian cancer. A finding of a variant of uncertain significance does not provide a basis for increased cancer surveillance or prophylactic procedures. Given that variant classification is often challenging, we also consider the role of multifactorial statistical analyses by large consortia and functional tests for this purpose.

scholarly journals Genetic testing for breast cancer risk, from BRCA1/2 to a seven gene panel: an ethical analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Erik Gustavsson ◽  
Giovanni Galvis ◽  
Niklas Juth
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Cost Effectiveness ◽  
Gene Panel ◽  
Special Focus ◽  
Secondary Findings ◽  
Variants Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Uncertain Significance

Abstract Background Genetic testing is moving from targeted investigations of monogenetic diseases to broader testing that may provide more information. For example, recent health economic studies of genetic testing for an increased risk of breast cancer suggest that it is associated with higher cost-effectiveness to screen for pathogenic variants in a seven gene panel rather than the usual two gene test for variants in BRCA1 and BRCA2. However, irrespective of the extent to which the screening of the panel is cost-effective, there may be ethical reasons to not screen for pathogenic variants in a panel, or to revise the way in which testing and disclosing of results are carried out. Main text In this paper we discuss the ethical aspects of genetic testing for an increased risk of breast cancer with a special focus on the ethical differences between screening for pathogenic variants in BRCA1/2 and a seven gene panel. The paper identifies that the panel increases the number of secondary findings as well as the number of variants of uncertain significance as two specific issues that call for ethical reflection. Conclusions We conclude that while the problem of handling secondary findings should not be overstated with regard to the panel, the fact that the panel also generate more variants of uncertain significance, give rise to a more complex set of problems that relate to the value of health as well as the value of autonomy. Therefore, it is insufficient to claim that the seven gene panel is preferable by only referring to the higher cost effectiveness of the panel.

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