Bilateral Prophylactic Oophorectomy and Ovarian Cancer Screening Following BRCA1/BRCA2 Mutation Testing

2003 ◽  
Vol 21 (21) ◽  
pp. 4034-4041 ◽  
Author(s):  
Marc D. Schwartz ◽  
Elizabeth Kaufman ◽  
Beth N. Peshkin ◽  
Claudine Isaacs ◽  
Chanita Hughes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Perceived Risk ◽  
Ca 125 ◽  
Test Results ◽  
Ovarian Cancer Screening ◽  
Prophylactic Oophorectomy ◽  
Brca1 Brca2 ◽  
The Impact ◽  
Test Result

Purpose: Despite the widespread availability of genetic testing for BRCA1/BRCA2 mutations, little is known about the impact of testing on ovarian cancer prevention and screening. For mutation testing to effect cancer mortality, positive test results must be followed by appropriate behavior change. In this study, we prospectively examined the impact of BRCA1/2 testing on the utilization of prophylactic oophorectomy and ovarian cancer screening. Participants and Methods: Participants were 289 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. We measured self-reported receipt of bilateral prophylactic oophorectomy (BPO) and utilization of CA-125 and transvaginal ultrasound (TVU) in the year following testing, and examined the impact of test results on these outcomes. In addition, we examined the role of sociodemographic, medical, family history, and psychological variables on the receipt of BPO, CA-125, and TVU. Results: Twenty-seven percent of mutation carriers, 5% of uninformative patients, and 2% of noncarriers received a BPO in the year following testing. In addition to test results, perceived risk for ovarian cancer and family history of ovarian cancer independently predicted receipt of BPO. The receipt of a positive test result was associated with increased utilization of CA-125 and TVU. Additional predictors included perceived risk for ovarian cancer (both CA-125 and TVU) and state anxiety (CA-125). Conclusion: These results demonstrate the significant behavioral impact of receiving a positive BRCA1/2 test result. The increased rate of oophorectomy among mutation carriers suggests that testing for BRCA1/2 mutations may ultimately impact ovarian cancer mortality.

scholarly journals Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening

2015 ◽  
Vol 33 (18) ◽  
pp. 2062-2071 ◽  
Author(s):  
Usha Menon ◽  
Andy Ryan ◽  
Jatinderpal Kalsi ◽  
Aleksandra Gentry-Maharaj ◽  
Anne Dawnay ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
United Kingdom ◽  
Cancer Screening ◽  
Ca 125 ◽  
Ovarian Cancer Screening ◽  
Collaborative Trial ◽  
The United Kingdom ◽  
Risk Algorithm ◽  
The Impact ◽  
Threshold Rule

Purpose Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. Patients and Methods In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. Results After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). Conclusion Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.

Impact of BRCA1/BRCA2 Mutation Testing on Psychologic Distress in a Clinic-Based Sample

2002 ◽  
Vol 20 (2) ◽  
pp. 514-520 ◽  
Author(s):  
Marc D. Schwartz ◽  
Beth N. Peshkin ◽  
Chanita Hughes ◽  
David Main ◽  
Claudine Isaacs ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Perceived Risk ◽  
Brca2 Mutation ◽  
Positive Test ◽  
Test Results ◽  
Brca1 And Brca2 ◽  
Negative Test ◽  
Psychologic Distress ◽  
The Impact ◽  
Test Result

PURPOSE: Despite the increasingly widespread availability of BRCA1 and BRCA2 genetic testing, little is known about the psychologic impact of such testing in the clinical setting. The objective of this study was to examine the long-term psychologic impact of receiving BRCA1/2 test results within a clinic-based testing program. PATIENTS AND METHODS: The participants were 279 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. At baseline (before genetic testing) and at 6 months after the disclosure of mutation status, we measured perceived risk for breast and ovarian cancer, cancer-specific distress, and general distress. We examined the impact of the test result on each of these outcomes at the 6-month follow-up. Analyses were conducted separately for probands and their relatives who were unaffected with cancer. RESULTS: We found no effect of test result among affected probands. Among unaffected relatives, we found that participants who received definitive negative test results exhibited significant reductions in perceived risk and distress compared with participants who received positive test results. Importantly, relatives who received positive test results did not exhibit increased distress or perceived risk. CONCLUSION: These results suggest that clinic-based BRCA1/2 testing can lead to psychologic benefits for individuals who receive negative test results. At 6 months after disclosure, those who receive positive or uninformative test results do not exhibit increased psychologic distress or perceived risk.

scholarly journals Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

2021 ◽  
pp. 849-861
Author(s):  
Sudeep Gupta ◽  
Senthil Rajappa ◽  
Suresh Advani ◽  
Amit Agarwal ◽  
Shyam Aggarwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Newly Diagnosed ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Fallopian Tube Cancer ◽  
Cross Sectional ◽  
Brca2 Mutations ◽  
Brca1 Brca2

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

Ovarian cancer screening in the general population

2019 ◽  
Vol 41 (3) ◽  
Author(s):  
Jérôme Mathis ◽  
Mohammed Amine Jellouli ◽  
Laura Sabiani ◽  
Joy Fest ◽  
Guillaume Blache ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Screening ◽  
General Population ◽  
Ultrasound Examination ◽  
Screening Method ◽  
Diagnostic Technique ◽  
Ca 125 ◽  
Ovarian Cancer Screening ◽  
Cancer Antigen ◽  
Diagnostic Management

AbstractBackgroundOvarian carcinoma is a poor prognosis cancer mainly due to its late diagnosis. Its incidence is relatively low but mortality is high. The symptomatology is only slightly specific, which complicates diagnostic management. It would therefore be interesting to be able to establish a diagnosis as early as possible in order to improve the prognosis of patients suffering from ovarian cancer.Materials and methodsCurrently, the combination of an ultrasound examination with a cancer antigen (CA)-125 assay is the most effective diagnostic technique, but not already admitted as a screening method. Therefore, we realized an exhaustive analysis of the most important studies in the last 15 years, in order to find new approaches in ovarian cancer screening.ResultsThe age for initiating screening and its frequency are issues that are not fully resolved. The false positives and morbidity that result from screening are currently notable limitations.ConclusionsThe latest data do not support effective screening in the general population.

scholarly journals Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
Antonios Kritikos ◽  
Julien Poissy ◽  
Antony Croxatto ◽  
Pierre-Yves Bochud ◽  
Jean-Luc Pagani ◽  
...  
Keyword(s):  
Intensive Care ◽  
High Risk ◽  
Invasive Candidiasis ◽  
Test Results ◽  
Beta Glucan ◽  
High Risk Patients ◽  
Therapeutic Decisions ◽  
Risk Patients ◽  
The Impact ◽  
Test Result

ABSTRACT The 1,3-beta-d-glucan (BDG) test is used for the diagnosis of invasive candidiasis (IC) in intensive care units (ICUs). However, its utility for patient management is unclear. This study assessed the impact of BDG test results on therapeutic decisions. This was a single-center observational study conducted in an ICU over two 6-month periods. All BDG test requests for the diagnosis of IC were analyzed. Before the second period, the ICU physicians received a pocket card instruction (algorithm) for targeted BDG testing in high-risk patients. The performance of the BDG test for IC diagnosis was assessed, as well as its impact on antifungal (AF) prescription. Overall, 72 patients had ≥1 BDG test, and 14 (19%) patients had an IC diagnosis. The BDG test results influenced therapeutic decisions in 41 (57%) cases. The impact of the BDG test was positive in 30 (73%) of them, as follows: AF abstention/interruption following a negative BDG result (n = 27), and AF initiation/continuation triggered by a positive BDG test result and subsequently confirmed IC (n = 3). In 10 (24%) cases, a positive BDG test result resulted in AF initiation/continuation with no further evidence of IC. A negative BDG result and AF abstention with subsequent IC diagnosis were observed in one case. The positive predictive value (PPV) of BDG was improved if testing was restricted to the algorithm’s indications (80% versus 36%, respectively). However, adherence to the algorithm was low (26%), and no benefit of the intervention was observed. The BDG result had an impact on therapeutic decisions in more than half of the cases, which consisted mainly of safe AF interruption/abstention. Targeted BDG testing in high-risk patients improves PPV but is difficult to achieve in ICU.

scholarly journals ‘Immunity Passports’ for SARS-CoV-2: an online experimental study of the impact of antibody test terminology on perceived risk and behaviour

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e040448
Author(s):  
Jo Waller ◽  
G James Rubin ◽  
Henry W W Potts ◽  
Abigail L Mottershaw ◽  
Theresa M Marteau
Keyword(s):  
Perceived Risk ◽  
Antibody Test ◽  
Open Science ◽  
Hand Washing ◽  
Physical Contact ◽  
Positive Test ◽  
Positive Test Result ◽  
Risk Of Infection ◽  
The Impact ◽  
Test Result

ObjectiveTo assess the impact of describing an antibody-positive test result using the terms Immunity and Passport or Certificate, alone or in combination, on perceived risk of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protective behaviours.Design2×3 experimental design.SettingOnline.Participants1204 adults from a UK research panel.InterventionParticipants were randomised to receive one of six descriptions of an antibody test and results showing SARS-CoV-2 antibodies, differing in the terms describing the type of test (Immunity vs Antibody) and the test result (Passport vs Certificate vs Test).Main outcome measuresPrimary outcome: proportion of participants perceiving no risk of infection with SARS-CoV-2 given an antibody-positive test result. Other outcomes include: intended changes to frequency of hand washing and physical distancing.ResultsWhen using the term Immunity (vs Antibody), 19.1% of participants (95% CI 16.1% to 22.5%) (vs 9.8% (95% CI 7.5% to 12.4%)) perceived no risk of catching coronavirus given an antibody-positive test result (adjusted OR (AOR): 2.91 (95% CI 1.52 to 5.55)). Using the terms Passport or Certificate—as opposed to Test—had no significant effect (AOR: 1.24 (95% CI 0.62 to 2.48) and AOR: 0.96 (95% CI 0.47 to 1.99) respectively). There was no significant interaction between the effects of the test and result terminology. Across groups, perceiving no risk of infection was associated with an intention to wash hands less frequently (AOR: 2.32 (95% CI 1.25 to 4.28)); there was no significant association with intended avoidance of physical contact (AOR: 1.37 (95% CI 0.93 to 2.03)).ConclusionsUsing the term Immunity (vs Antibody) to describe antibody tests for SARS-CoV-2 increases the proportion of people believing that an antibody-positive result means they have no risk of catching coronavirus in the future, a perception that may be associated with less frequent hand washing.Trial registration numberOpen Science Framework: https://osf.io/tjwz8/files/

Correlation of CA-125 and RECIST evaluation in recurrent ovarian cancer (ROC): Results from a randomized phase III study of trabectedin (T) with pegylated liposomal doxorubicin (PLD) versus PLD alone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5550-5550
Author(s):  
T. J. Herzog ◽  
J. B. Vermorken ◽  
E. Pujade-Lauraine ◽  
J. Li ◽  
E. Bayever ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Value ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Ca 125 ◽  
Open Label ◽  
Significant Prolongation ◽  
Phase Iii Study ◽  
The Impact

5550 Background: OVA-301, an open-label, multicenter, randomized phase III study comparing the combination of T and PLD to PLD alone in 672 ovarian cancer patients, showed significant prolongation in Progression-Free Survival (PFS) and higher Objective Response (OR) in the combination arm (T-PLD) by three separate assessments, investigator assessment (IA), independent radiology (IR) and oncology review (IO). The purpose of this analysis is to examine: 1) the impact of early changes in CA-125 over the subsequent best OR by RECIST; 2) the concordance between best OR determined by CA-125 and RECIST; 3) the value of CA-125 to predict radiological response. Methods: Tumor assessments by imaging and CA-125 were performed at baseline, and every 8 weeks during study in both arms. Radiological tumor assessment, regardless of CA-125 changes, determined the study conduct. Early CA-125 changes were those assessed at the first and second evaluation. Analyses were based on “all randomized patients.” Results: Response rate by RECIST (IR)/CA-125 was 28%/48% for T-PLD vs. 19%/33% for PLD. The association between CA-125 and RECIST response was stronger for IA relative to IR/IO, with 79% concordance for both arms, 65% overall positive predictive value (PPV) and 89% negative predictive value (NPV) for IA and 74%/75% concordance, 46%/49% PPV and 93%/92% NPV for IR/IO. Early CA-125 changes were assessed in 514 patients. Early ≥25% CA-125 decreases in the first/second evaluation occurred in 85%/95% of RECIST responders in the T-PLD arm and in 81/82% responders treated with PLD. Conclusions: The predictive value of CA-125 response was high and similar in both arms. The addition of T to PLD resulted in superior efficacy in this patient population as assessed by IA, IR and IO, with a favorable trend for CA-125 response assessment. RECIST response was preceded by a significant CA-125 decrease in a high proportion of patients. [Table: see text]

Preliminary evidence of activity of pralatrexate in relapsed/refractory ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15557-e15557
Author(s):  
Nashat Y. Gabrail ◽  
Carrie L. Smith
Keyword(s):  
Ovarian Cancer ◽  
Renal Impairment ◽  
Renal Insufficiency ◽  
Solid Tumors ◽  
Hematological Malignancies ◽  
Folate Receptor ◽  
Ca 125 ◽  
Clinical Activity ◽  
Weekly Dose ◽  
The Impact

e15557 Background: Pralatrexate, a novel antifolate, is approved in the US for the treatment of relapsed/refractory peripheral T-cell lymphoma at a dose of 30mg/m2 weekly for 6 weeks of a 7-week cycle. Previous studies in solid tumors have focused on a q2w schedule at 190mg/m2. As pralatrexate is 30-40% renally excreted, an ongoing renal impairment study is investigating the impact of mild, moderate and severe renal impairment on pralatrexate distribution in patients with hematological malignancies and solid tumors. As folate receptor alpha is frequently overexpressed in epithelial ovarian cancers, we hypothesized that ovarian cancer may be a target for pralatrexate treatment and therefore have included a number of ovarian cancer patients in this trial. Methods: Patients with solid tumors and hematological malignancies were enrolled in a phase I clinical trial. Patients are treated in cohorts depending on renal function normal, mild renal insufficiency, moderate renal insufficiency and severe non-dialysis dependent renal failure. This analysis is limited to 6 patients with refractory ovarian cancer. The dose of pralatrexate is 30mg/m2 weekly for 6 weeks of a 7-week cycle, with dose adjustment depending on toxicity. Results: The 6 patients, all with stage 4 refractory ovarian cancer had received 4 or more prior chemotherapy regimens and had refractory disease, defined as, nonresponsive to the last chemotherapy regimen or progression within 3 months of the last dose of chemotherapy. Of the 6 patients, 2 experienced objective responses lasting 9 months and 4 months respectively. Disease response was assessed by CA- 125 and RECIST criteria. Two patients experienced stable disease for 4 months and 5 months respectively. One patient had grade 5 mucositis after the second weekly dose and one patient had progressive disease after disease stabilization for 3 months. Conclusions: Pralatrexate given at a dose of 30mg/m2 to patients with refractory ovarian cancer has demonstrable activity that needs to be confirmed in well-designed efficacy trials. Importantly, this is the first demonstration of clinical activity in a solid tumor at the currently approved dose.

Examining screening behaviors at a high-risk ovarian cancer clinic.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13047-e13047
Author(s):  
Courtney Lynam-Scherr ◽  
Kisha T Hope ◽  
Irene B. Helenowski ◽  
Masha Kocherginsky ◽  
Melissa Keene ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Insurance Coverage ◽  
Prophylactic Surgery ◽  
Ca 125 ◽  
Ovarian Cancer Risk ◽  
Race Ethnicity ◽  
The Impact ◽  
Screening Behaviors ◽  
High Risk Clinic

e13047 Background: Women with deleterious BRCA1/2mutations have a significantly increased lifetime risk to develop ovarian cancer. Prophylactic surgery can significantly reduce ovarian cancer risk. The Northwestern Ovarian Cancer Early Detection and Prevention Program (NOCEDPP) was established to monitor this high-risk population prior to risk-reducing surgery. For such patients, providers in the NOCEDPP recommend screening with CA-125 and transvaginal ultrasound (TVUS) biannually. The aim of this study was to examine screening rates of women who have not had surgery but attend the NOCEDPP. Methods: We reviewed electronic health records of 1,662 women who attended the NOCEDPP clinic between October 2005 – October 2015. Demographic and clinical characteristics and utilization of screening were analyzed retrospectively using descriptive statistics and Kruskal-Wallis H-tests to examine differences in screening rates by age, race, ethnicity and insurance type. Results: Of the 1,662 women initially identified, 385 had a known BRCA mutation, 303 had an appointment with at least 6 months between first and last procedure – the sample included in the final analysis. Compared with women ages 35-45 (median = 1.91) and 45+ (median = 1.18), women ages 20-35 attended the most screenings per year (median = 2.12) p = 0.001, a rate consistent with biannual recommendations. There were no significant differences in screening rate by race, ethnicity, or insurance coverage. Conclusions: Despite changes in national guidelines, providers in our high-risk clinic continue to recommend CA-125 and TVUS biannually. Our preliminary data indicates patients’ attendance is uninfluenced by race, ethnicity, or insurance coverage. Further exploration of the impact of age is warranted. Implication of findings indicate a high-risk clinic may positively impact screening behaviors above and beyond factors typically associated with non-adherence.

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