scholarly journals The first Japanese nationwide multicenter study of BRCA mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of BRCA (CHARLOTTE)

2019 ◽  
Vol 29 (6) ◽  
pp. 1043-1049 ◽  
Author(s):  
Takayuki Enomoto ◽  
Daisuke Aoki ◽  
Kana Hattori ◽  
Masahisa Jinushi ◽  
Junzo Kigawa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Serous Carcinoma ◽  
High Grade ◽  
Cancer Genetic ◽  
Cross Sectional ◽  
Cancer Data ◽  
Increased Risk ◽  
The Cross

IntroductionBRCA gene mutations are associated with hereditary ovarian cancer. BRCA plays a key role in genome integrity, and mutations result in an increased risk for ovarian cancer. Although various guidelines recommend BRCA testing in patients with ovarian cancer, data on germline BRCA (gBRCA) mutation frequency in ovarian cancer in Japan are scarce.ObjectiveThis study aimed to determine gBRCA1/2 mutations in Japanese patients with ovarian cancer, stratified by clinicopathological characteristics, and to assess patients’ satisfaction with pre-test genetic counseling.MethodsThe CHARLOTTE study (CHARacterizing the cross-sectionaL approach to Ovarian cancer: geneTic TEsting of BRCA; UMIN000025597) is the first large multicenter epidemiological survey of Japanese women, aged ≥20, with newly diagnosed ovarian cancer (epithelial, primary peritoneal, or fallopian tube cancer), with histologically confirmed specimens. Patients were enrolled sequentially and underwent pre-test genetic counseling for BRCA testing. Blood samples were centrally tested for the presence or absence of known gBRCA mutations. A questionnaire was used to assess patient satisfaction with pre-test genetic counseling.ResultsA total of 634 patients with a mean age of 56.9 years were included. Most patients (84.2%) had epithelial ovarian cancer, and 51.1% had FIGO stage III–IV cancer. Nearly all patients (99.5%) received genetic counseling before the BRCA testing, either by an obstetrician-gynecologist (42.0%) or a clinical geneticist (42.0%). The overall prevalence of gBRCA1/2 mutations was 14.7% (93/634), with gBRCA1 mutations (9.9%) more common than gBRCA2 mutations (4.7%). High-grade serous carcinoma showed a prevalence of gBRCA mutations of 28.5%. Most patients were satisfied with pre-test counseling, irrespective of the service provider’s professional position.DiscussionPatients with high-grade serous carcinoma and family history of ovarian cancer had a slightly higher prevalence of gBRCA mutations, but none of the subgroups had considerably high gBRCA mutation prevalence. These data suggest that gBRCA testing should be carried out in all patients with ovarian cancer.

scholarly journals Japan CHARLOTTE: Characterizing the cross-sectional approach to ovarian cancer: Genetic testing of BRCA

2017 ◽  
Vol 28 ◽  
pp. v350
Author(s):  
T. Sugiyama ◽  
D. Aoki ◽  
T. Enomoto ◽  
N. Takeshima ◽  
Y. Watanabe ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Genetic ◽  
Cross Sectional ◽  
The Cross

scholarly journals BRCA testing in women with high-grade serous ovarian cancer: gynecologic oncologist-initiated testing compared with genetics referral

2020 ◽  
Vol 30 (11) ◽  
pp. 1757-1761
Author(s):  
Sabrina Piedimonte ◽  
Joanne Power ◽  
William D Foulkes ◽  
Evan Weber ◽  
Laura Palma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Median Time ◽  
High Grade ◽  
Peritoneal Carcinoma ◽  
Gynecologic Oncologist ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Genetics Referral

ObjectiveUp to 15% of patients with high-grade serous ovarian, tubal, or peritoneal carcinoma harbor a mutation in BRCA genes. Early notion of mutation status may facilitate counseling, predict prognosis, and increase access to Parp-inhibitors. The aim of this study was to examine the rate of germline genetic testing in a retrospective cohort of women with high-grade serous ovarian, tubal, or peritoneal carcinoma to determine if a new pilot project of gynecologic oncologist-initiated genetic testing improved the rate of testing, after 1 year of implementation.MethodsGynecologic oncology-initiated genetic testing was implemented at a single university hospital center with input and collaboration from gynecological oncologists, nurses, and genetic counselors. All patients diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma after August 2017 were offered gynecologic oncologist- initiated genetic testing for a panel of 13 hereditary breast and ovarian cancer susceptibility genes. Data from this group was then compared with a historic cohort of patients who received traditional genetic counseling between January 2014 and August 2017 (control group). Patients that had genetic testing through a clinical trial were excluded. The primary outcome was the uptake of genetic testing in both groups. Secondary outcomes included difference in time from diagnosis to genetic result between both cohorts. Data was analyzed using SPSS 25.0 and medians (ranges) were reported.ResultsA total of 152 women with high-grade serous ovarian, tubal, or peritoneal carcinoma were included in this study. Between January 2014 to July 2017 there were 108 patients with high-grade serous ovarian, tubal, or peritoneal carcinoma, among which 50.9% (n=54) underwent genetic testing following referral to genetics. The prevalence of BRCA pathogenic variants was 25.9% (14/54): 9.2% (5/54) in BRCA1 and 16.7% (9/54) in BRCA2. The median time from diagnosis to genetics referral was 53 days (range; 3–751), and median time from diagnosis to test result disclosure was 186 days (range; 15–938). After 1 year of implementation of the gynecologic oncologist-initiated genetic testing model, among 44 women diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma, 86.2% underwent genetic testing. The median time from diagnosis to result disclosure decreased to 58 days, representing a reduction of 128 days, or 4.27 months (P<0.001). Reasons for non-testing included refusal, death, and follow-up at another hospital. The prevalence of germline BRCA1/2 pathogenic variants was 21% (8/38).ConclusionGynecologic oncologist-initiated genetic testing at the time of high-grade serous ovarian, tubal, or peritoneal carcinoma diagnosis leads to increased uptake and decreased delays in testing compared with referral for traditional genetic counseling.

Psychosocial Issues in Genetic Testing for Breast/Ovarian Cancer

2021 ◽  
pp. 95-101
Author(s):  
Mary Jane Esplen ◽  
Jonathan Hunter ◽  
Eveline M. A. Bleiker
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Develop Breast Cancer ◽  
Elevated Risk ◽  
Breast Cancers ◽  
Cancer Genetic ◽  
Social Challenges ◽  
Mutation Carriers

Approximately 10% of all breast cancers are due to hereditary factors, with the majority caused by mutations in two autosomal dominant breast cancer genes, BRCA1 and BRCA2. Mutations in these genes are associated with cumulative risks of breast cancer of 72% in BRCA1 mutation carriers and 69% in BRCA2 mutation carriers by age 80. Mutation carriers who develop breast cancer have elevated risk for contralateral breast cancer. BRCA1/2 mutations also place women at elevated risk for ovarian cancer. Genetic counseling and testing are available to individuals, with or without cancer, to inform health-related decision-making. While genetic knowledge offers opportunities for prevention, including prophylactic risk-reducing surgery, a number of psychological and social challenges have been identified in the BRCA1/2 population. This chapter provides a broad overview of seminal research on the psychosocial impacts of genetic testing in BRCA1/2 with the goal of helping readers better identify, evaluate, and treat psychosocial challenges stemming from the process of genetic testing. Identifiable risk factors for psychosocial distress during the genetic counseling process are summarized. The chapter points toward key psychometric instruments designed to support psychosocial screening in cancer genetic populations. Further, a summary of intervention strategies to support psychosocial adaptation to genetic testing is provided.

scholarly journals Immunohistochemical expression of p53 in Type I and II epithelial ovarian cancer among Sudanese women: a cross-sectional study

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1739
Author(s):  
Aisha Osman Mohamed ◽  
Nazik Elmalaika Husain ◽  
Rawia Eljaili Elmassry ◽  
Lubna Alnageeb ◽  
Mohammed Elhassan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
P53 Overexpression ◽  
Cross Sectional ◽  
Over Expression ◽  
Tumor Types

Background: Epithelial ovarian cancer (EOC) represents the leading cause of death from gynecologic malignancies worldwide. In Sudan, ovarian cancer represents the fourth most frequent tumors among females. TP53 somatic mutations is a defining feature of ovarian high-grade serous carcinoma. However, p53 sequencing is not feasible in most low- and middle-income countries, like Sudan, and its frequency varies greatly. The study aimed to determine the frequency of p53 overexpression and its relationship with tumor types I and II and tumor grade among Sudanese women with EOC. Methods: In this cross-sectional, hospital-based study a total of 114 paraffin-embedded tissue blocks previously diagnosed as epithelial ovarian cancer were collected from six governmental hospitals in Khartoum state, Sudan, in the period 2013-2016. Immunohistochemistry was performed on tissue microarray slides to measure the protein expression of p53 in the EOC. Results: Overexpression of p53 was detected in 35.1% (n=40/114) of  EOC samples, with a higher frequency in women with Type II 53.7% (n= 29/54)  than type I 18.5% (n= 10/54)  (P= 0.000). Also, a high frequency of p53 overexpression was evident in 49.2% (n= 30/61) of high-grade carcinoma compared with 16.7% (n= 1/6) of non-graded borderline tumors, and in 19.1% (n= 9/47) of low-grade tumors (P= 0.003). A high-grade serous carcinoma harbor p53 overexpression in 53.7% (n= 29/54) and none of low-grade serous carcinoma harbor p53 overexpression. Our result showed a significant association between p53 overexpression and tumor types and grades (P = 0.000 and 0.003, respectively) Conclusion:  p53 over-expression was detected in one-third of Sudanese women with EOC.  It was more common in type II EOC and high-grade serous, but negative in low-grade serous tumors. Our result showed a significant association between p53 over-expression and tumor type and grade, and can help discriminate between high- and low-grade serous carcinomas.

scholarly journals A randomized trial of a breast/ovarian cancer genetic testing decision aid used as a communication aid during genetic counseling

2008 ◽  
Vol 17 (8) ◽  
pp. 844-854 ◽  
Author(s):  
Claire E. Wakefield ◽  
Bettina Meiser ◽  
Judi Homewood ◽  
Alan Taylor ◽  
Margaret Gleeson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Randomized Trial ◽  
Decision Aid ◽  
Cancer Genetic ◽  
Communication Aid

scholarly journals Targeting progesterone signaling prevents metastatic ovarian cancer

2020 ◽  
Vol 117 (50) ◽  
pp. 31993-32004
Author(s):  
Olga Kim ◽  
Eun Young Park ◽  
Sun Young Kwon ◽  
Sojin Shin ◽  
Robert E. Emerson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Deleterious Mutation ◽  
Peritoneal Metastases ◽  
Cancer Development ◽  
Serous Carcinoma ◽  
Cancer Type ◽  
High Grade ◽  
Primary Tumors ◽  
High Risk Populations ◽  
Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

scholarly journals National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer

2017 ◽  
Vol 35 (34) ◽  
pp. 3800-3806 ◽  
Author(s):  
Christopher P. Childers ◽  
Kimberly K. Childers ◽  
Melinda Maggard-Gibbons ◽  
James Macinko
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Unmet Need ◽  
Cancer Control ◽  
The United States ◽  
Eligibility Criteria ◽  
Cross Sectional ◽  
Age Of Diagnosis ◽  
History Of ◽  
Interview Survey

Purpose In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria. Methods We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey. Eligible patients were adult females with a history of BC and/or OC meeting select 2017 National Comprehensive Cancer Network eligibility criteria on the basis of age of diagnosis and family history. Outcomes included the proportion of individuals reporting a history of discussing genetic testing with a health professional, being advised to undergo genetic testing, or undergoing genetic testing for BC or OC. Results Of 47,218 women, 2.7% had a BC history and 0.4% had an OC history. For BC, 35.6% met one or more select eligibility criteria; of those, 29.0% discussed, 20.2% were advised to undergo, and 15.3% underwent genetic testing. Testing rates for individual eligibility criteria ranged from 6.2% (relative with OC) to 18.2% (diagnosis ≤ 45 years of age). For OC, 15.1% discussed, 13.1% were advised to undergo, and 10.5% underwent testing. Using only four BC eligibility criteria and all patients with OC, an estimated 1.2 to 1.3 million individuals failed to receive testing. Conclusion Fewer than one in five individuals with a history of BC or OC meeting select National Cancer Comprehensive Network criteria have undergone genetic testing. Most have never discussed testing with a health care provider. Large national efforts are warranted to address this unmet need.

scholarly journals Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 547
Author(s):  
Iolia Akaev ◽  
Siavash Rahimi ◽  
Olubukola Onifade ◽  
Francis John Edward Gardner ◽  
David Castells-Rufas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unknown Origin ◽  
Parp Inhibitors ◽  
Serous Carcinoma ◽  
High Grade ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Epithelial Cancers ◽  
Pathogenic Variants ◽  
Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

scholarly journals Cost-Effectiveness of Colorectal Cancer Genetic Testing

2021 ◽  
Vol 18 (16) ◽  
pp. 8330
Author(s):  
Abdul Rahman Ramdzan ◽  
Mohd Rizal Abdul Manaf ◽  
Azimatun Noor Aizuddin ◽  
Zarina A. Latiff ◽  
Keng Wee Teik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Testing ◽  
Cost Effectiveness ◽  
Cancer Survival ◽  
Screening Method ◽  
Targeted Prevention ◽  
Activity Based Costing ◽  
Cross Sectional ◽  
Increased Risk ◽  
The Cost

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. Approximately 3–5% of CRCs are associated with hereditary cancer syndromes. Individuals who harbor germline mutations are at an increased risk of developing early onset CRC, as well as extracolonic tumors. Genetic testing can identify genes that cause these syndromes. Early detection could facilitate the initiation of targeted prevention strategies and surveillance for CRC patients and their families. The aim of this study was to determine the cost-effectiveness of CRC genetic testing. We utilized a cross-sectional design to determine the cost-effectiveness of CRC genetic testing as compared to the usual screening method (iFOBT) from the provider’s perspective. Data on costs and health-related quality of life (HRQoL) of 200 CRC patients from three specialist general hospitals were collected. A mixed-methods approach of activity-based costing, top-down costing, and extracted information from a clinical pathway was used to estimate provider costs. Patients and family members’ HRQoL were measured using the EQ-5D-5L questionnaire. Data from the Malaysian Study on Cancer Survival (MySCan) were used to calculate patient survival. Cost-effectiveness was measured as cost per life-year (LY) and cost per quality-adjusted life-year (QALY). The provider cost for CRC genetic testing was high as compared to that for the current screening method. The current practice for screening is cost-saving as compared to genetic testing. Using a 10-year survival analysis, the estimated number of LYs gained for CRC patients through genetic testing was 0.92 years, and the number of QALYs gained was 1.53 years. The cost per LY gained and cost per QALY gained were calculated. The incremental cost-effectiveness ratio (ICER) showed that genetic testing dominates iFOBT testing. CRC genetic testing is cost-effective and could be considered as routine CRC screening for clinical practice.

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