Ovarian Cancer Risk Assessment Research Articles

Clinical Decision Making Using Ovarian Cancer Risk Assessment

Although any adnexal abnormality found at imaging can be concerning for an ovarian malignancy, the clinician must perform an evaluation to decide if the actual likelihood of malignancy justifies the risk of surgery. When determining the likelihood of an asymptomatic, incidental adnexal mass being malignant, the provider must answer one important question: Do the clinical findings warrant the potential morbidity of surgery? This article will focus on the decision making that goes into such an evaluation. A patient's medical history, physical examination, CA-125 level, and imaging characteristics are all factors that impact the ultimate decision of whether a patient can be observed with repeat imaging or should proceed to surgical evaluation.

Risk Assessment and Genetic Testing for Ovarian Cancer

Prevention of ovarian cancer starts with identifying women at high risk for this deadly disease. Once identified, these women can be offered risk-reducing options such as oral contraceptives and bilateral salpingo-oophorectomy. In this review, strategies for identifying high-risk individuals and the clinical utility of genetic testing for BRCA1 and BRCA2 will be discussed. To offer potentially life-saving interventions for at-risk family members, we propose that every woman newly diagnosed with ovarian cancer be offered genetic testing for BRCA1 and BRCA2 genes because mutations in these genes are the strongest known predictors of ovarian cancer risk.

Refining BRCA1 and BRCA2 penetrance estimates in the clinic

Genetic testing for mutations in BRCA1 and BRCA2 can provide important information to women and help guide clinical management decisions regarding interventions such as oophorectomy to reduce cancer risk. However, variability exists in risks of breast and ovarian cancer in individual BRCA1 and BRCA2 mutation carriers, with potential contributing factors including genotype-phenotype correlations, modifier genes, environmental and reproductive exposures, and the impact of interventions. Ultimately, the clinical goal is to provide individualized assessment of breast and ovarian cancer risk to BRCA1 and BRCA2 mutation carriers accounting for these variables to aid decision-making. This article discusses factors affecting the penetrance of cancer risks in BRCA1/2 mutation carriers.

Modification of Ovarian Cancer Risk by BRCA1/2-Interacting Genes in a Multicenter Cohort of BRCA1/2 Mutation Carriers

Inherited BRCA1/2 mutations confer elevated ovarian cancer risk. Knowledge of factors that can improve ovarian cancer risk assessment in BRCA1/2 mutation carriers is important because no effective early detection for ovarian cancers exists. A cohort of 1,575 BRCA1 and 856 BRCA2 mutation carriers was used to evaluate haplotypes at ATM, BARD1, BRIP1, CTIP, MRE11, NBS1, RAD50, RAD51, and TOPBP1 in ovarian cancer risk. In BRCA1 carriers, no associations were observed with ATM, BARD1, CTIP, RAD50, RAD51, or TOPBP1. At BRIP1, an association was observed for one haplotype with a multiple testing corrected P (P(corr)) = 0.012, although no individual haplotype was significant. At MRE11, statistically significant associations were observed for one haplotype (P(corr) = 0.007). At NBS1, we observed a P(corr) = 0.024 for haplotypes. In BRCA2 carriers, no associations were observed with CTIP, NBS1, RAD50, or TOPBP1. Rare haplotypes at ATM (P(corr) = 0.044) and BARD1 (P(corr) = 0.012) were associated with ovarian cancer risk. At BRIP1, two common haplotypes were significantly associated with ovarian cancer risk (P(corr) = 0.011). At MRE11, we observed a significant haplotype association (P(corr) = 0.012), and at RAD51, one common haplotype was significantly associated with ovarian cancer risk (P(corr) = 0.026). Variants in genes that interact biologically withBRCA1 and/or BRCA2 may be associated with modified ovarian cancer risk in women who carry BRCA1/2 mutations.

Social‐cognitive aspects of underserved Latinas preparing to undergo genetic cancer risk assessment for hereditary breast and ovarian cancer

As Latinos are a growing ethnic group in the United States, it is important to understand the socio-cultural factors that may be associated with cancer screening and prevention in this population. The socio-cultural factors that may affect preparedness to undergo genetic cancer risk assessment (GCRA) deserve particular attention. The pre-GCRA period can provide insight into variables that may influence how medically underserved Latinas, with limited health resources and access, understand hereditary cancer information and subsequently implement cancer risk management recommendations. This study explores social, cognitive and cultural variables in Latinas prior to undergoing GCRA. The study sample consisted of low-income, underserved Latinas referred for GCRA because of a personal and/or family history of breast or ovarian cancer. Acculturation, cancer-specific fatalism, self-efficacy and social support were assessed prior to GCRA. Fifty Latinas (mean age=40.1+/-7.7) completed instruments; 86% had invasive cancer, 78% spoke primarily Spanish and 61% were of Mexican ancestry. Low levels of acculturation (n=50, mean=9.0+/-5.8) and cancer-specific fatalism (n=43, mean=5.6+/-3.2), but relatively high self-efficacy (n=49, mean=40.9+/-7.8) and social support (n=49, mean=37.3+/-8.7) were reported. Cancer-specific fatalism and self-efficacy were inversely correlated (r=-0.47, p=0.002). Those over age 38 at the time of cancer diagnosis reported higher acculturation (mean=11.4+/-7.2, p=0.02) and social support (mean=40.5+/-1.2, p=0.05). These findings suggest that medically underserved Latinas may already possess some of the necessary skills to successfully approach the GCRA process, but that special attention should be given to cultural factors.

Risk Assessment and Genetic Counseling for Hereditary Breast and Ovarian Cancer: Recommendations of the National Society of Genetic Counselors

These cancer genetic counseling recommendations describe the medical, psychosocial and ethical implications of identifying at-risk individuals for hereditary breast and ovarian cancer (HBOC) through cancer risk assessment, with or without genetic susceptibility testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors' Familial Cancer Risk Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment as well as the professional expertise of genetic counselors with significant experience in education and counseling regarding hereditary breast and ovarian cancer. Critical components of the process include the ascertainment of medical and family histories, determination and communication of cancer risk, assessment of risk perception, education regarding the genetics of HBOC, discussion of molecular testing for HBOC if appropriate (including benefits, risks and limitations) and any necessary follow-up. These recommendations do not dictate an exclusive course of management or guarantee a specific outcome. Moreover, they do not replace the professional judgment of a health care provider based on the clinical situation of a client.

Ovarian Cancer Risk Assessment

Ovarian Cancer Risk Assessment

Ovarian Cancer Risk Assessment

Papers on Current Clinical and Basic Investigation: Tuesday, May 9, 2006: Donald F. Richasdson Memorial Prize Paper

Risk assessment in non-Ashkenazi women attending a cancer risk assessment clinic

6127 Background: Our Women's Cancer Screening and Prevention Project, a multidisciplinary cancer risk assessment clinic, was launched in April 2001. Our objective was to determine the demand for a women's cancer early detection and prevention program in a public metropolitan hospital serving immigrant women. Methods: Patient recruitment was accomplished via outreach strategies targeting community organizations and inreach programs within the institution. Patients visiting the clinic were seen by both gynecologic and medical oncologists, and underwent in-depth interviews, physical examinations and discussion of risk profiles. Risk categories were assigned for each woman using our IRB-approved questionnaire, mutation probability models, and discussion of each case at our weekly medical meeting. Recommendations were made concerning genetic counseling and testing, surveillance, risk reduction strategies and available clinical trials. Results: Among the 163 patients who have attended our clinic, 150 (92%) are not Ashkenazi. Our patients are Latina (43%), Caucasian (29%), African-American (19%) and Asian (8%). The median age of patients seen was 39, (range 20 - 76). 30% of our patients were classified as high risk (greater than 15% chance of harboring a deleterious BRCA 1 or 2 mutation), and surveillance and risk reduction recommendations were commensurate with this assessment. These high risk patients included 23 Latinas, 10 Asians and 7 African Americans. Results of genetic counseling and testing are pending at this time. Conclusions: The role and potential impact or breast and ovarian cancer risk assessment in populations not commonly associated with hereditary breast and ovarian cancers deserves further attention. Supported by the Lynne Cohen Foundation for Ovarian Cancer Research. No significant financial relationships to disclose.

Specific keynote: ovarian cancer risk assessment and the potential for early detection.

Specific keynote: ovarian cancer risk assessment and the potential for early detection.

Risk of ovarian cancer in breast-cancer patients with a family history of breast or ovarian cancer: a population-based cohort study

Patients with breast cancer who have mutations in the high penetrance genes BRCA1 and BRCA2, have an increased risk of ovarian cancer. Because these mutations are rare, easily obtained information such as age and family history of breast or ovarian cancer might be preferable for assessment of ovarian cancer risk in clinical practice. We linked data from the Swedish Cancer Register to the Swedish Generation Register and generated a cohort of 30552 breast-cancer patients born after 1931, with information on breast and ovarian cancer diagnosis from 146117 first-degree relatives. Standardised incidence ratios (SIRs) with 95% CIs were calculated with nationwide rates of ovarian cancer, adjusted for age and calendar year. During a mean follow-up of 6 years, 122 incident ovarian cancers were identified in the cohort, yielding an overall SIR of 2.0 (95% CI 1.6-2.4). The risk was higher in breast-cancer patients diagnosed before the age of 40 years, with a family history of breast cancer (5.6; 1.8-13.1) or ovarian cancer (17.0; 3.5-50.0). A consistently increased risk was noted in patients with a relative who was diagnosed before the age of 50 years, with either breast or ovarian cancer. Women with a family history of ovarian cancer have an almost 10% risk of developing ovarian cancer before the age of 70. In young women with breast cancer, the risk of ovarian cancer is greatly raised when a family history of breast or ovarian cancer is present. Close medical surveillance, and perhaps even prophylactic oophorectomy, might be justified in high-risk groups.

Psychological Adjustment to Familial-Genetic Risk Assessment for Ovarian Cancer: Predictors of Nonadherence to Surveillance Recommendations

Objective. To evaluate whether self-report measures of psychological distress and perceived risk were associated with nonadherence to recommended ovarian cancer surveillance.Methods. Eighty-three patients attending the Familial Ovarian Cancer Clinic (FOCC) at Princess Margaret Hospital were assessed psychosocially prior to and during initial familial-genetic assessment and then monitored for adherence with recommended follow-up surveillance over a period of 12–18 months. The assessment protocol included an investigator-designed clinic questionnaire, the State–Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CESD), Life Orientation Test (LOT), Medical Outcomes Study Social Support Survey (MOSSS), Texas Inventory of Grief, and the COPE. Nonadherence was measured in terms of unexplained absences at one or two recommended and scheduled surveillance appointments following the familial-genetic assessment.Results. Univariate tests revealed a significant association between higher perception of ovarian cancer risk, as assessed immediately after the familial-genetic risk assessment in the clinic and nonadherence to physician-recommended surveillance (χ2 (2, N = 83) = 9.75, P < 0.008). Empirically based estimates of risk, conveyed by the clinic team to subjects, were not significantly associated with nonadherence (χ2 (2, N = 83) = 0.19, P = 0.91). Logistic regression analysis revealed that subjects who perceived themselves to be at high ovarian cancer risk were five times more likely to be nonadherent than participants who perceived themselves to be at low or medium ovarian cancer risk.Conclusions. These results suggest that higher self-perceived risk may predict adherence difficulties to recommended surveillance in women attending a familial-genetic risk clinic.

A Longitudinal Study of Psychological Adjustment to Familial Genetic Risk Assessment for Ovarian Cancer

Abstract Objectives. To evaluate the psychological adjustment of women during initial genetic ovarian cancer risk assessment and at clinic follow-up, 6–12 months later. Methods. Sixty-five subjects were assessed with the Centre for Epidemiological Studies Depression Scale (CESD), Spielberger's State Anxiety Inventory, and an 18-item, investigator-designed questionnaire yielding self-report on screening responses, worry about increased risk, identification of cancer-related deaths in relatives, worry about future cancer risks of daughters, alteration of future plans as a result of ovarian cancer risk, etc. Results. Thirty-three percent of subjects had CESD scores above the established cutoff for depression at baseline and 38% had scores above cutoff at follow-up. Sixteen percent of subjects had state scores on the State-Trait Anxiety Inventory higher than 1 standard deviation above average (norm) at baseline, while only 6% had scores higher than 1 SD above average at follow-up. Conclusion. To identify factors associated with self-reported depression at follow-up, a series of demographic and self-reported variables (e.g., presence of identified problems in family, impact of genetic risk information, concern for daughter in the future) were entered in a multiple regression analysis with the CESD follow-up score as the dependent variable. Only one predictor accounted for a significant amount of variance in depression scores. Concern for daughter's risk in the future was associated with higher depression scores at follow-up ( R = 0.33, P R 2 = 11%).

A Longitudinal Study of Psychological Adjustment to Familial Genetic Risk Assessment for Ovarian Cancer

Objectives. To evaluate the psychological adjustment of women during initial genetic ovarian cancer risk assessment and at clinic follow-up, 6–12 months later.Methods. Sixty-five subjects were assessed with the Centre for Epidemiological Studies Depression Scale (CESD), Spielberger's State Anxiety Inventory, and an 18-item, investigator-designed questionnaire yielding self-report on screening responses, worry about increased risk, identification of cancer-related deaths in relatives, worry about future cancer risks of daughters, alteration of future plans as a result of ovarian cancer risk, etc.Results. Thirty-three percent of subjects had CESD scores above the established cutoff for depression at baseline and 38% had scores above cutoff at follow-up. Sixteen percent of subjects had state scores on the State-Trait Anxiety Inventory higher than 1 standard deviation above average (norm) at baseline, while only 6% had scores higher than 1 SD above average at follow-up.Conclusion. To identify factors associated with self-reported depression at follow-up, a series of demographic and self-reported variables (e.g., presence of identified problems in family, impact of genetic risk information, concern for daughter in the future) were entered in a multiple regression analysis with the CESD follow-up score as the dependent variable. Only one predictor accounted for a significant amount of variance in depression scores. Concern for daughter's risk in the future was associated with higher depression scores at follow-up (R = 0.33, P < 0.02, R2 = 11%).

Ultrasound assessment of ovarian cancer risk in postmenopausal women with CA125 elevation.

We have previously shown that, in asymptomatic post-menopausal women, serum CA125 elevation is associated with a 36-fold increase in risk of ovarian cancer. This study was undertaken to assess the value of pelvic ultrasound for further stratification of ovarian cancer risk. Of 22 000 post-menopausal women, aged ≥ 45 participating in an Ovarian Cancer Screening Trial, 741 with a CA125 ≥ 30 U ml−1 underwent pelvic ultrasonography. Twenty index cancers (primary invasive epithelial carcinomas of the ovary and fallopian tube) were diagnosed amongst these 741 women during a median follow-up of 6.8 years. Ultrasound results separated the women with CA125 elevation into two groups. Those with normal ovarian morphology had a cumulative risk (CR) of index cancer of 0.15% (95% confidence interval (CI) 0.02–1.12) which is similar to that of the entire population of 22 000 women (0.22%, 95% CI 0.18–0.30). In contrast, women with abnormal ovarian morphology had a CR of 24% (15–37) and a significantly increased relative risk (RR) of 327 (156–683). Ultrasound can effectively separate post-menopausal women with raised CA125 levels into those with normal scan findings who are not at increased risk of index cancer and those with abnormal findings who are at substantially increased risk of index cancer. © 1999 Cancer Research Campaign