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.

scholarly journals Extended gene panel testing in lobular breast cancer

2021 ◽  
Author(s):  
Elke M. van Veen ◽  
D. Gareth Evans ◽  
Elaine F. Harkness ◽  
Helen J. Byers ◽  
Jamie M. Ellingford ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Detection Rate ◽  
Gene Panel ◽  
Lobular Breast Cancer ◽  
Germline Variants ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
Increased Risk

AbstractPurpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

scholarly journals Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lucie G. Hallenstein ◽  
Carol Sorensen ◽  
Lorraine Hodgson ◽  
Shelly Wen ◽  
Justin Westhuyzen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Genetics ◽  
Eligibility Criteria ◽  
Pathogenic Variants ◽  
Genetics Services ◽  
Age Of Diagnosis ◽  
Over Time

Abstract Background Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014–2018. Methods Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. Results There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014–2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. Conclusions Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

Integration of germline multigene panel testing into breast and gynecologic oncology clinics.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 164-164
Author(s):  
Mariella Tejada ◽  
June YiJuan Hou ◽  
Katherine D. Crew ◽  
Melissa Kate Accordino ◽  
Kevin Kalinsky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Genetic Testing ◽  
Clinical Decision Making ◽  
Genetic Test ◽  
Gynecologic Oncology ◽  
Clinical Decision ◽  
Test Results ◽  
Panel Testing ◽  
Genetic Test Results

164 Background: Germline genetic testing plays an important role in informing cancer screening and risk-reducing strategies, as well as treatment decisions with PARP inhibitors for BRCA-associated malignancies. Referrals to clinical genetics for pre-test counseling and results disclosure can be delayed due to financial and logistical barriers, which may ultimately delay clinical decision-making. Our study objective was to understand patient attitudes, knowledge, and anxiety/distress with point-of-care (POC) genetic testing in breast and gynecologic oncology clinics. Methods: We enrolled patients with early-stage breast cancer undergoing neoadjuvant treatment, metastatic breast cancer, ovarian cancer, or endometrial cancer undergoing POC multigene panel testing with their primary oncologist, rather than a genetic counselor. Pre-test counseling came from discussion with their primary oncologist. Participants completed a survey at time of genetic testing and one after return of genetic test results. Validated measures of genetic testing knowledge, cancer-related distress, and attitudes towards genetic testing were included. Descriptive statistics were generated for all data collected and paired t-tests were conducted for baseline and follow-up comparisons. Results: We enrolled 106 subjects, of which 97 completed the baseline survey. All participants were female with a mean age of 61.5 years (SD 13.5). The cohort consisted of participants with the following tumor types: 80 breast, 2 ovarian, and 16 endometrial. Almost 44% of women identified as Hispanic/Latina, 55% had highest level of education of community/technical college or less, and 51.2% reported annual incomes of less than $50,000. Forty-seven percent of participants had adequate baseline genetic testing knowledge scores (defined as at least 50% correct responses). A majority of participants (86.6%) had positive attitudes toward undergoing genetic testing. Results of genetic testing revealed 11 participants (11.3%) with pathogenic or likely pathogenic variants (of which 36.3% were in BRCA1/2), 25 (25.8%) with variants of unknown significance (VUS), and 61 (62.9%) with benign or likely benign results. The mean cancer-related distress score (scale from 15 to 60, higher score indicates higher levels of distress) was 32.78 (SD 9.74) at baseline and 26.5 (SD 8.9) after receiving genetic testing results (p = 0.002). Genetic test results informed cancer treatment decisions regarding medications and surgery in 15% and 13% of patients, respectively, the majority of which were breast cancer patients. Conclusions: As genetic testing is more frequently used for clinical decision-making it is important to develop ways to efficiently integrate POC testing in the oncology clinics. We demonstrated that POC genetic testing for breast and gynecologic cancers is feasible and can inform clinical decision-making.

Prevalence and spectrum of pathogenic variants among patients with multiple primary cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10595-10595
Author(s):  
Brittany L. Bychkovsky ◽  
Min-Tzu Lo ◽  
Yuan Tian ◽  
Amal Yussuf ◽  
Carrie Horton ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cancer Diagnosis ◽  
Age At Diagnosis ◽  
Multiple Primary Cancers ◽  
Cancer Type ◽  
Exact Test ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Multiple Primary ◽  
Brca1 Brca2

10595 Background: Multiple primary cancers (MPCs) are a hallmark of cancer predisposition syndromes. We aim to characterize the frequency of germline pathogenic/likely pathogenic variants (PVs) among patients with MPCs. Herein we report the frequency of PVs by sex, number of cancers and age at diagnosis among a laboratory-based cohort of patients with MPCs. Methods: Patients with MPCs who underwent germline genetic testing with Ambry Genetics from 3/2012 to 12/2016 were included in our cohort. Eligible individuals had multigene panel testing, which included 21 genes, at minimum: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53. Clinical factors including age at diagnosis, age at testing and cancer type were obtained from test requisition forms and clinical notes. Patients with > 1 PVs were excluded from the analysis. Using Rv.3.3.3., the frequencies of PVs by sex, number of cancers and age at diagnosis were compared using two-sided χ2 tests or Fisher’s exact test when the number was < 10. Results: Of the 9820 patients with MPCs tested for the 21 genes above, 104 (1.1%) had multiple PVs and were excluded. Among the remaining 9716 patients in the analytic cohort, most were female (91.1%) and white (71.0%). The median age at testing was 63 years (IQR: 16) and the median ages of first and second cancer diagnosis were 49 (IQR: 18) and 58 (IQR: 17) years, respectively. Overall, 1406 (14.5%) were found to have PVs: 14.3% of females and 16.2% of males. The prevalence of PVs increased with the number of primary cancers (PCs) as follows, 2 PCs: 13.1% (95% CI:12.4-13.8%), 3 PCs: 15.9% (95% CI:14.0-18.0%), >4 PCs: 18.0% (95% CI:13.7-23.3%), (p < 0.01). Among patients with 2 PCs (n = 8145), differences in the prevalence of PVs by age at diagnosis were significant: 2 PCs diagnosed at an age < 50 (13.5%, 95% CI:12.0-15.1%), 1 PC diagnosed at an age < 50 (14.8%, 95% CI:13.4-16.5%), 2 PCs diagnosed at age >50 years (12.1%, 95% CI: 11.1-13.2%), (p = 0.01). PVs were most frequently identified in: BRCA2 (2.2%) BRCA1 (2.0%), CHEK2 (1.9%) and ATM (1.5%). There were also significant differences in the frequencies of PVs in BRCA1, BRCA2 and MLH1 by sex (p < 0.05). Conclusions: These data demonstrate a high frequency of germline PVs among both males and females with MPC. The frequency of PVs was higher among patients with a higher number of PCs. Differences in the prevalence of PVs by age at cancer diagnosis while significant, were not meaningful as 12.1% of individuals with 2 PCs diagnosed at age >50 years had germline PVs. Limitations include the homogenous testing population (predominately female and white) and small numbers in some patient categories. These data may aid in counseling patients with MPCs and their families as well as encourage less restrictive genetic testing of this population. Further analysis of PV frequencies by specific cancer combinations was conducted and will follow.

Multi-gene hereditary cancer testing among men with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1532-1532
Author(s):  
Krystal Brown ◽  
Gregory Sampang Calip ◽  
Ryan Bernhisel ◽  
Brent Evans ◽  
Eric Thomas Rosenthal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Clinical Information ◽  
Gene Panel ◽  
Age At Diagnosis ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
Personal Diagnosis

1532 Background: All men with a personal diagnosis of breast cancer (BC) are candidates for BRCA1/2 genetic testing, as pathogenic variants (PVs) in these genes have a known association with BC risk in both men and women. As additional genes with known BC risk in women are now routinely included in multi-gene panel testing, we evaluated the outcomes of multi-gene panel testing in a large cohort of men with BC. Methods: This analysis includes the results of commercial genetic testing for 1,358 men with BC usinga multi-gene pan-cancer panel between September 2013 and January 2017. Clinical information was obtained from provider-completed test request forms. Age at diagnosis, personal, and family history were compared for men with PVs in BRCA1/2 versus non- BRCA1/2 genes. Results: Overall, 207 (15.2%) men with BC were found to carry a PV, where 147 (10.8%) men had a PV in BRCA1/2 ( BRCA1, 0.7%; BRCA2, 10.2%) and 60 (4.4%) men had a PV in a non- BRCA1/2 gene ( CHEK2, 2.0%; ATM, 1.0%; PALB2, 1.0%; BARD1, 0.2%; NBN, 0.2%; MSH6, 0.1%; BRIP1, 0.1%; CDH1, 0.1%; CDKN2A, 0.1%; MLH1, 0.1%, TP53, 0.1%). There were no substantial differences in the median age-at-diagnosis for men without a PV (65) compared to those with a BRCA1/2 PV (66) or a non- BRCA1/2 PV (63). Prostate cancer was the most common additional malignancy among all men with BC (9.0%), with a similar incidence among men with a BRCA1/2 PV (9.2%) and a non- BRCA1/2 PV (8.3%). In addition, 1.4% of men with a BRCA1/2 PV and 3.3% of men with a non- BRCA1/2 PV had a second BC. A family history of breast and/or ovarian cancer was present in 44.4% of the testing cohort, 66.7% of men with a BRCA1/2 PV, and 48.3% of men with a non- BRCA1/2 PV. This is consistent with the relative penetrance of BRCA1/2 and other genes included here. There were no other substantial differences in family history among BRCA1/2 PV carriers versus non- BRCA1/2 PV carriers. Conclusions: Close to a third of all PVs identified here in men with BC were in a gene other than BRCA1/2. There were no obvious differences in the clinical presentation of men with a BRCA1/2 PV compared to men with a PV in another gene or no PV at all. Collectively, this suggests that multi-gene panel testing is appropriate for all men with BC, regardless of other personal or family history.

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 Implications of Multigene Panel Testing on Psychosocial Outcomes: A Comparison of Patients With Pancreatic and Breast or Ovarian Cancer

2021 ◽  
pp. 235-244
Author(s):  
Cathryn Koptiuch ◽  
Whitney F. Espinel ◽  
Wendy K. Kohlmann ◽  
Jingsong Zhao ◽  
Kimberly A. Kaphingst
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Genetic Test ◽  
Emotional Reactions ◽  
Test Results ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Genetic Test Results ◽  
Multigene Panel Testing ◽  
Multigene Panel

PURPOSE National Comprehensive Cancer Network guidelines for germline genetic testing have included pancreatic cancer in the context of additional family cancer history for many years but this was not recommended for patients with pancreatic ductal adenocarcinoma (PDAC) independent of a family history until 2019. This hypothesis-generating study reports the results from multigene panel testing for PDAC patients at an academic medical center. PATIENTS AND METHODS This prospective longitudinal feasibility study examined responses to genetic counseling and multigene panel testing among PDAC and breast or ovarian cancer (BrOv) patients between October 2016 and November 2017. Pre- and post-test surveys assessed perceptions of genetic risk and testing, recall, comprehension, and emotional reactions to results using open-ended and closed-ended items. RESULTS Forty-six BrOv and 33 PDAC patients were enrolled, and 44 BrOv and 31 PDAC participants underwent genetic testing. Seven pathogenic variants were identified in six BrOv participants (13.6%), and three pathogenic variants were identified in three PDAC participants (9.7%). The majority of both cohorts expressed similar attitudes about the importance of genetic testing for their personal and family medical management and expressed accurate understanding of implications of their results. Although sample size was small, there were no significant differences between the BrOv and PDAC cohorts for positive or negative emotions. CONCLUSION This study points to high rates of positive emotions and low rates of negative emotions following genetic test results, suggesting that the emotional reactions to genetic test results are similar for patients with BrOv and PDAC, despite poor prognosis with PDAC diagnoses. Because of the unique needs of the PDAC population following diagnosis, a multidisciplinary approach to germline genetic testing following diagnosis may result in best patient and family member outcomes.

scholarly journals 167P Role of the multi-gene panel testing for detection of pathogenic variants in patients with hereditary bilateral breast cancer

2021 ◽  
Vol 32 ◽  
pp. S432-S433
Author(s):  
C. Filorizzo ◽  
D. Fanale ◽  
L. Incorvaia ◽  
N. Barraco ◽  
M. Bono ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bilateral Breast Cancer ◽  
Gene Panel ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing

scholarly journals Expanding the search for germline pathogenic variants for breast cancer. How far should we go and how high should we jump? The missed opportunity!

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Hikmat Abdel-Razeq
Keyword(s):  
Breast Cancer ◽  
Brca1 And Brca2 ◽  
Healthy Women ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of ◽  
Risk Reducing ◽  
Current Guidelines ◽  
Missed Opportunity

Since the identification of BRCA1 and BRCA2 genes 3 decades ago, genetic testing and genetic counseling have become an integral part of routine clinical practice. The risk of breast cancer among carriers of germline pathogenic variants, like BRCA1 and BRCA2, is well established. Risk-reducing interventions, including bilateral mastectomies and salpingo-oophorectomies are both effective and have become more acceptable. Many researchers and professional societies view current guidelines as restrictive and may miss many at-risk women, and are calling to expand testing to include all patients with breast cancer, regardless of their personal or family history of cancer, while others are calling for wider adoption to even include all healthy women at age 30 or older. This review will address expanding testing in two directions; horizontally to include more patients, and even healthy women, and vertically to include more genes using next-generation sequencing-based multi-gene panel testing.

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