Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2.

PURPOSE: This study examined baseline knowledge, beliefs, and risk perceptions among a group of 200 women with breast and/or ovarian cancer who participated in a trial designed to improve decision making about genetic testing for BRCA1 and BRCA2. PATIENTS AND METHODS: Women were identified by self-referral, physician referral, and tumor registry extraction and invited to participate in a randomized trial in which testing for BRCA1 and BRCA2 was offered free of charge. Subjects completed baseline questionnaires and interviews that assessed knowledge, attitudes, and perceptions of risk of having an alteration in BRCA1 or BRCA2. RESULTS: Sixty percent of women overestimated their chances of having a BRCA1 or BRCA2 mutation compared with estimates from a BRCA1/BRCA2 risk model. Women who have at least three relatives with breast or ovarian cancer were one third (95% confidence interval, 0.2 to 0.6) as likely to overestimate their risk of having a BRCA1 or BRCA2 mutation compared with women who have two or fewer affected relatives. Knowledge was limited about BRCA1 and BRCA2 mutations and cancer risk associated with gene mutations. Eighty-four percent of the women indicated a probable or definite interest in testing. CONCLUSION: A high proportion of the high-risk women in this study had knowledge deficits about BRCA1 and BRCA2 and overestimated their risk of having a mutation. Although some degree of caution should be used in generalizing the results of this study to practice settings, the data provide insight into the challenges clinicians will face in communicating with patients about cancer genetics.     

Long-term satisfaction and quality of life following risk reducing surgery in <Emphasis Type="Italic">BRCA1/2</Emphasis> mutation carriers

Background

As BRCA1/2 testing becomes more routine, questions remain about long-term satisfaction and quality of life following testing. Previously, we described long term distress and risk management outcomes among women with BRCA1/2 mutations. This study addresses positive psychological outcomes in BRCA1/2 carriers, describing decision satisfaction and quality of life in the years following testing.

Methods

We evaluated satisfaction with testing and management decisions among 144 BRCA1/2 carriers. Prior to genetic testing, we assessed family history, sociodemographics and distress. At a mean of 5.3 years post-testing, we assessed management decisions, satisfaction with decisions and, among women with cancer, quality of life.

Results

Overall, satisfaction with decision making was high. Women who had risk reducing mastectomy or oophorectomy were more satisfied with management decisions. Participants who obtained a risk reducing oophorectomy were more satisfied with their genetic testing decision. Among affected carriers, high pretest anxiety was associated with poorer quality of life and having had risk reducing mastectomy prior to testing was associated with better quality of life. The negative impact of pre-test anxiety was diminished among women who had mastectomies before testing.

Conclusions

BRCA1/2 carriers are satisfied with their testing and risk management decisions and report good quality of life years after testing. Having risk reducing surgery predicts increased satisfaction and improved quality of life.

     

Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast cancer. Whether women with breast cancer who have inherited mutations in these genes have a different outcome after breast conservation therapy than women with "sporadic" cancer is unresolved. Consequently, we compared the outcomes after breast conservation therapy in Ashkenazi women with or without germline mutations in BRCA1 and/or BRCA2 (hereafter called BRCA). METHODS: We studied 305 women of Ashkenazi Jewish descent undergoing breast-conserving treatment for 329 invasive breast cancers. We reviewed their clinical records, retrieved their archival tissue samples, and tested those samples for the founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. Genetic results were linked to clinical data and outcomes by univariate and multivariate analyses. All Pvalues are two-sided. RESULTS: We detected mutations in BRCA genes in 28 of 305 women. Women with BRCA mutations were more likely to be diagnosed with cancer before the age of 50 years (P<.001) and to have lymph node involvement (P =.04). Ipsilateral breast tumor recurrence was more common in women with BRCA mutations, although this did not reach statistical significance (relative risk [RR] = 1.79; 95% confidence interval [CI] = 0.64-5.03). Women with mutations were more likely to develop contralateral breast cancer (RR = 3.50; 95% CI = 1.78-8.74; P =.001). Distant disease-free survival was shorter in women with mutations (66.2% versus 84.3% at 10 years; P =.05), as was breast cancer-specific survival (71.9% versus 87.2% at 10 years; P =.02). Tumor stage and nodal status, but not mutation status, were predictive of distant disease-free and breast cancer-specific survival in multivariate analysis. CONCLUSIONS: Women with BRCA founder mutations are at increased risk for breast cancer-related events after breast conservation. However, mutation status is not an independent predictor of survival and should not influence decisions regarding adjuvant therapy. The increased contralateral breast cancer risk in women heterozygous for BRCA mutations mandates careful surveillance.     

Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers

BACKGROUND: Women with mutations in the BRCA1 or BRCA2 cancer susceptibility genes face unique choices regarding management of their high risk for breast and ovarian cancer that impact their reproductive options. In order to explore women's preferences for management of elevated cancer risk, we evaluated the decisions of BRCA1/2 mutation carriers about contraception, prophylactic surgery, and family planning. METHODS: An internet-based questionnaire assessing high-risk women's preferences about cancer risk management and reproductive options was designed, pilot-tested and administered electronically to 284 participants of an internet-based advocacy group for women with BRCA1/2 mutations. RESULTS: Two hundred and thirteen eligible participants completed the majority of the survey. Mean age was 34 years; 66% were BRCA1 mutation carriers and 34% were BRCA2 mutation carriers. Most women (92%) had used oral contraceptive pills. About 88% of responders reported frequent or extreme worry about transmitting the mutation to their children. Despite their high level of worry, few responders said they would likely consider using assisted reproduction technologies such as a pregnancy surrogate (3%), cryopreservation of oocytes or embryos (8%), or pre-implantation genetic diagnosis (PGD) to select embryos without BRCA1/2 mutations (13%). CONCLUSIONS: Although they expressed substantial concern about transmitting BRCA1/2 mutations to their children, only a minority of the high-risk women surveyed were likely to consider currently available assisted reproductive strategies. Further research is necessary to explore the risk management preferences of patients with inherited cancer predisposition, and to incorporate these preferences into clinical care.     

Reproductive issues for women with BRCA mutations

Women carrying BRCA1 and BRCA2 mutations face difficult and confusing reproductive decisions that fall into three categories: issues relating to risk-reducing surgeries, issues relating to use of oral contraceptives/tubal ligation, and issues relating to pregnancy and breastfeeding. Risk-reducing surgeries may confer survival benefits, but they also affect quality of life. Oral contraceptives potentially protect mutation carriers against ovarian cancer but increase the risk of early-onset breast cancer, and evidence for the efficacy of tubal ligation in reducing ovarian cancer risk in BRCA mutation carriers is contradictory. Women with BRCA mutations may increase their risk of breast cancer by becoming pregnant before age 40 years, but breastfeeding may decrease risk of breast cancer in women with BRCA mutations, regardless of age. BRCA mutation carriers desiring to become pregnant must deal with a variety of psychosocial issues, some with significant ethical implications, with minimal guidance from research.     

BRCA1 testing with definitive results: a prospective study of psychological distress in a large clinic-based sample

AIM: To examine the short-term psychological impact of receiving definite results concerning BRCA1 mutation status in a clinical setting. METHODS: A test was offered for consecutive sample of 395 women from 53 families with demonstrated BRCA1 mutations. The sample included 50 women with a personal history of cancer, and 345 women without. Of the 287 women who chose to be tested and participated in the study, 79% of those with cancer 33% of those without cancer had a demonstrated BRCA1 mutation. Psychological distress was measured with the hospital anxiety and depression scale (HADS), the general health questionnaire (GHQ-28), the impact of event scale (IES) and Beck's hopelessness scale (BHS) at the time the patients were offered testing and six weeks after receiving the test result. RESULTS: No significant changes were found in psychological distress from baseline to follow-up in any groups. Women with cancer were significantly more distressed than those without both at baseline and at six weeks, while women without cancer had levels of psychological distress comparable to or lower than normative data as measured by HADS. CONCLUSIONS: Our sample had a low level of psychological distress at baseline. Receiving a definite positive or negative result on the BRCA1 test had minimal effects on short-term psychological distress. These findings indicate that establishing a special psychological service in relation to predictive BRCA1 testing could be superfluous.     

Satisfaction with ovarian carcinoma risk-reduction strategies among women at high risk for breast and ovarian carcinoma

BACKGROUND:

Women who are at high risk for breast and ovarian cancer have 2 major management options to reduce their risk of ovarian cancer: periodic screening (PS) or risk‐reducing salpingo‐oophorectomy (RRSO). Little is known regarding patient satisfaction levels with risk‐reduction strategies. Thus, the authors sought to determine levels of patient satisfaction with PS versus RRSO and to identify factors that may influence satisfaction.

METHODS:

As part of a larger study, women who received testing for the breast cancer genes BRCA1 and BRCA2 were sent a follow‐up questionnaire packet to explore issues related to cancer risk reduction. The authors report on the results from a variety of validated instruments, including the Satisfaction With Decision (SWD) scale, focused on the choice between PS and RRSO.

RESULTS:

In total, 544 surveys were mailed, and 313 responses were received (58%). The overall satisfaction rate among respondents was high. The median SWD score was significantly higher in the RRSO group compared with the PS group (P < .001). BRCA mutation carriers had higher median SWD scores regardless of management type (P = .01). Low satisfaction scores were associated with high levels of uncertainty and the perception that the decision between PS and RRSO was difficult to make (P = .001). Satisfaction was unrelated to demographics, clinical factors, or concerns of cancer risk.

CONCLUSIONS:

In the current study, the majority of women who were at high risk for breast and ovarian cancer were satisfied with their choice of risk‐reduction strategy. Difficulty with decision making was associated with lower satisfaction levels. Improved education and support through the decision‐making process may enhance overall levels of satisfaction. Cancer 2011. © 2010 American Cancer Society.     

Medical management of women with inherited predisposition to breast cancer: indications and procedures for mammographic screening

Women identified or suspected as carriers of mutations in BRCA1 or BRCA2 susceptibility genes have a high risk to develop an early breast cancer and thus, require appropriate management. Some consensus guidelines were provided for women at hereditary risk and two possible strategies of prevention are suggested: breast cancer screening and prophylactic surgery. We present the French recommendations for breast cancer surveillance and discuss the justification, indications and modalities of mammographic screening. Screening by annual mammography is recommended from age 30 years in experienced centers, in association with semi-annual clinical breast examination from age 20 years. These recommendations apply to women who were identified as carriers of a cancer-predisposing mutation of BRCA1 or BRCA2 genes. In families for whom any mutation of the two genes could be identified, the same modalities apply also to women with a higher probability than 25% of being a carrier. We present here an illustration of the calculation of such probabilities from two example-pedigrees.     

A multicenter study of supportive-expressive group therapy for women with BRCA1/BRCA2 mutations

BACKGROUND: Women with a BRCA1/BRCA2 mutation experience significant challenges. These include decision-making regarding surgical options and notification to offspring and family, along with a sense of isolation, which may lead to psychological and emotional distress. The current study developed, standardized, and conducted preliminary testing of a supportive-expressive group therapy intervention designed to address these challenges. METHODS: Seventy women with a BRCA1/BRCA2 mutation recruited from familial cancer risk clinics participated in 12 sessions of supportive-expressive group therapy that lasted 6 months. Before and after measures of psychosocial functioning, knowledge, and surveillance/surgery activities were completed. RESULTS: Sixty-seven women completed the intervention. Significant improvements were observed in psychosocial functioning: cancer worries (P = 0.005), anxiety (P = 0.033), and depression (P = 0.015). Knowledge level and surveillance levels were high at baseline and there were no significant changes postintervention. A significant number of women made decisions concerning prophylactic surgery (oophorectomy/mastectomy) during and after the intervention. CONCLUSIONS: The feasibility of a supportive-expressive group for BRCA1/BRCA2 mutation carriers was demonstrated. Findings from the study are consistent with an effective intervention. However, further research is required using a randomized controlled study design.     

Factors associated with decisions about clinical BRCA1/2 testing.

Testing for mutations in BRCA1 and BRCA2 can provide important information about breast and ovarian cancer risk to a small but identifiable subgroup of women. Women who test positive for a BRCA1/2 mutation can pursue more aggressive cancer surveillance and prevention regimens. Among families with known mutations, women who test negative may avoid unnecessary interventions. Currently, little is known about the factors associated with the use of clinical BRCA1/2 testing. The objective of this study was to determine the factors associated with decisions about clinical BRCA1/2 testing among women undergoing clinical BRCA1/2 counseling through a retrospective cohort study of women who participated in a university-based clinic offering breast cancer risk assessment, genetic counseling, and BRCA1/2 testing between January 1996 and April 1998. From the 251 eligible women who responded to a follow-up survey, 125 (50%) had undergone or were undergoing BRCA1/2 testing, 86 (34%) had decided not to undergo testing, and 40 (16%) were undecided about testing. After multivariate adjustment, we found that women who chose to undergo BRCA1/2 testing were more likely to have a known familial mutation [odds ratio (OR), 7.46; 95% confidence interval (CI), 0.97-62.16], more likely to be Ashkenazi Jewish (OR, 6.37; 95% CI, 2.68-15.12), more likely to want cancer risk information for family members (OR, 1.93; 95% CI, 0.99-4.14), more likely to want information about ovarian cancer risk (OR, 1.69; 95% CI, 1.18-3.69), and less likely to be concerned about insurance or job discrimination (OR, 0.45; 95% CI, 0.21-0.94). These associations were also found in the subgroup of women with a predicted probability of a BRCA1 mutation of 25%. Our study suggests that approximately half of eligible women choose to undergo clinical BRCA1/2 testing after participating in counseling. Women who have the highest risk of carrying a mutation, and thus the greatest probability of gaining some useful information from the test results, are most likely to undergo testing. Women who undergo testing are also more interested in ovarian cancer risk information and less concerned about job and insurance discrimination.     

Feasibility evaluation of an online tool to guide decisions for BRCA1/2 mutation carriers

Women with BRCA1 or BRCA2 (BRCA1/2) mutations face difficult decisions about managing their high risks of breast and ovarian cancer. We developed an online tool to guide decisions about cancer risk reduction (available at: http://brcatool.stanford.edu), and recruited patients and clinicians to test its feasibility. We developed questionnaires for women with BRCA1/2 mutations and clinicians involved in their care, incorporating the System Usability Scale (SUS) and the Center for Healthcare Evaluation Provider Satisfaction Questionnaire (CHCE-PSQ). We enrolled BRCA1/2 mutation carriers who were seen by local physicians or participating in a national advocacy organization, and we enrolled clinicians practicing at Stanford University and in the surrounding community. Forty BRCA1/2 mutation carriers and 16 clinicians participated. Both groups found the tool easy to use, with SUS scores of 82.5–85 on a scale of 1–100; we did not observe differences according to patient age or gene mutation. General satisfaction was high, with a mean score of 4.28 (standard deviation (SD) 0.96) for patients, and 4.38 (SD 0.89) for clinicians, on a scale of 1–5. Most patients (77.5 %) were comfortable using the tool at home. Both patients and clinicians agreed that the decision tool could improve patient–doctor encounters (mean scores 4.50 and 4.69, on a 1–5 scale). Patients and health care providers rated the decision tool highly on measures of usability and clinical relevance. These results will guide a larger study of the tool’s impact on clinical decisions.     

Utilization of screening and preventive surgery among unaffected carriers of a BRCA1 or BRCA2 gene mutation.

OBJECTIVE: Women who are carriers of BRCA gene mutations have an elevated lifetime risk of developing breast or ovarian cancer. Although a number of risk-reducing options are currently available to mutation carriers, uncertainty exists in terms of their efficacy. A systematic review of the literature was conducted to describe the utilization of screening and preventive surgery among unaffected mutation carriers in the face of uncertainty.METHODS: MEDLINE, PubMed, and CANCERLIT, English-only computerized literature searches were done to identify articles pertaining to decisions made by unaffected BRCA mutation carriers to reduce risk of breast and ovarian cancer. Studies were required to include information on choices taken by at-risk women following disclosure of a positive BRCA test.RESULTS: Only seven studies (5 American and 2 Dutch studies) were identified. The proportion of mutation carriers who chose preventive surgery over screening varied widely across the studies, ranging from 0% to 54% for prophylactic mastectomy and from 13% to 53% for prophylactic oophorectomy. Furthermore, a significant minority of women who chose surveillance failed to comply with the recommended schedule.CONCLUSION: There is considerable variability within and between countries in risk reduction strategies utilized by healthy mutation carriers. This variability may relate to differences in (1) population characteristics; (2) recommendations for follow-up care of unaffected carriers; (3) prevailing values towards body integrity, femininity, and preventive surgery; and (4) health care funding systems. Future research needs to provide further insight into factors influencing women's decisions to adopt various risk reduction strategies.     

Complementary medicine use before and 1 year following genetic testing for BRCA1/2 mutations.

PURPOSE: We explored change in complementary and alternative medicine (CAM) use by unaffected women and cancer survivors from enrollment into a randomized BRCA1/2 testing program to CAM use 1 year following results disclosure.METHODS: A cohort of 243 high-risk women completed questionnaires at enrollment into a BRCA1/2 randomized trial and 1 year post results disclosure. Uses of several CAMs for cancer prevention were explored, including ingestible, behavioral, and physical modalities. Assessment of the change in CAM use from baseline to 1 year follow-up was conducted using a repeated self-administered questionnaire. Correlates of the number of CAMs used at 1 year were explored using multivariable linear regression models.RESULTS: Among the subset of women who changed their CAM behavior from enrollment to 1 year following BRCA1/2 results disclosure, there was a significantly higher proportion who changed from no CAM use to CAM use among the overall cohort (P=0.01), among women without cancer at enrollment (P=0.003), among women found to be BRCA1/2 carriers (P=0.03), and among women randomized to the genetic counseling intervention arm of the study (P=0.009). Number of CAMs used at 1 year was positively associated with number of CAMs used at baseline, sunscreen use, and BRCA1/2 mutation status.CONCLUSION: High-risk women who have received BRCA1/2 counseling and testing frequently adopt new CAM use in the first year after learning their genetic status. Mutation carriers frequently initiate CAM use after learning their genetic status as part of their cancer preventive regimen. Further studies are warranted to determine the efficacy of CAM-related strategies for cancer prevention.     

A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a Gynecologic Oncology Group study.

BACKGROUND: Women who are genetically predisposed to ovarian cancer are at very high risk of developing this disease. Although risk-reducing salpingo-oophorectomy (RRSO) and various screening regimens are currently recommended to reduce ovarian cancer risk, the optimal management strategy has not been established nor have multiple additional issues been adequately addressed. We developed a collaboration among the Clinical Genetics Branch (National Cancer Institute's Intramural Research Program), the Gynecologic Oncology Group (GOG), and the Cancer Genetics Network to address these issues. METHODS: This is a prospective, international, two-cohort, nonrandomized study of women at genetic risk of ovarian cancer, who chose either to undergo RRSO or screening, at study enrollment. Primary study objectives include quantifying and comparing ovarian and breast cancer incidence in the two study groups, assessing feasibility and selected performance characteristics of a novel ovarian cancer screening strategy (the Risk of Ovarian Cancer Algorithm), evaluating various aspects of quality of life and nononcologic morbidity related to various interventions in at-risk women, and creating a biospecimen repository for subsequent translational research. RESULTS: Study accrual is complete as of November 2006; 2,605 participants enrolled: 1,030 (40%) into the surgical cohort and 1,575 (60%) into the screening cohort. Five years of prospective follow-up ends in November 2011. Verification of BRCA mutation carrier status is under way, either through patient-provided reports from clinical genetic testing done before enrollment or through research-based genetic testing being conducted as part of the protocol. Patient eligibility is currently under evaluation and baseline, surgical, pathology, and outcome data are still being collected. The study design and selected baseline characteristics of cohort members are summarized. CONCLUSION: This National Cancer Institute intramural/extramural collaboration will provide invaluable prospectively collected observational data on women at high familial ovarian cancer risk, including substantial numbers of women carrying BRCA1/2 mutations. These data will aid in elucidating the effect of RRSO on breast/ovarian cancer risk and the effects of two management strategies, on quality of life and other issues that may influence patient care, as well as providing preliminary estimates of test specificity and positive predictive value of a novel ovarian cancer screening strategy.     

Experience with breast cancer,pre-screening perceived susceptibility and the psychological impact of screening

This prospective study examined whether the psychological impact of organized mammography screening is influenced by women's pre-existing experience with breast cancer and perceived susceptibility (PS) to the disease. From a target population of 16,886, a random sample of women with a normal screening finding and all women with a false positive or a benign biopsy finding were included (N=1942). Data were collected with postal questionnaires 1-month before screening invitation and 2 and 12 months after screening. Response rate was 63% at baseline; 86, and 80% of the baseline participants responded to the follow-ups. Psychological impact was measured as anxiety (STAI-S), depression (BDI), health-related concerns (IAS), and breast cancer-specific beliefs and concerns. Data was analyzed with repeated measures analyses of variance, with estimates of effect size based on Eta-squared. Women with breast cancer experience had higher risk perception already before screening invitation; after screening they were also more distressed. Women with high PS were more distressed than women with low PS also at pre-invitation. The distress was not alleviated by screening, but instead remained even after normal mammograms. Experience and PS did not influence responses to different screening findings. Of the finding groups, false positives experienced most adverse effects: their risk perception increased and they reported most post-screening breast cancer-specific concerns. Furthermore, they became more frequent in breast self-examination (BSE) despite a simultaneous decrease in BSE self-efficacy. Our findings suggest that women with high PS and women with false positive screening finding may need individualized counseling and follow-up as much as women with a family history of breast cancer. Besides medical risk factors, women's own perceptions of susceptibility should be discussed during the screening process.     

Adaptation of couples living with a high risk of breast/ovarian cancer and the association with risk-reducing surgery

Women who carry BRCA1/2 mutations have a significantly elevated risk for breast and ovarian cancer. The positive test result and subsequent decisions about risk reducing behaviors can evoke distress, anxiety and worry. Psychological adaptation, or the process of coming to terms with the implications of a health threat, is an understudied construct in BRCA1/2 carriers. Little is known about adaptation and how it relates to other aspects of living at high risk for cancer. Even less is understood about adaptation among partners of BRCA1/2 carriers, and its relationship to adaptation in high risk individuals. Women at increased risk of breast/ovarian cancer (N?=?103) and a subset of partners (N?=?39) completed questionnaires that assessed risk management decisions (e.g. screening, risk-reducing surgery), dyadic coping, and the outcome of psychological adaptation. Women who had undergone risk-reducing mastectomy (RRM) had significantly higher levels of adaptation than those who had not (t?=?5.5, p?<?0.001, d?=?1.10). Partners of women who had undergone RRM also had higher levels of adaptation than partners of women who had not undergone RRM (t?=?3.7, p?=?0.01, d?=?0.96), though this association was not statistically significant when controlling for carriers’ adaptation. Undergoing risk-reducing oophorectomy was not associated with adaptation for BRCA1/2 carriers or their partners. Risk-reducing mastectomy is a significant event in the process of adapting to life at risk for hereditary cancer. Further, adaptation among partners is highly related to adaptation in carriers. These results aid in the understanding of the experience of couples living with cancer risk and the medical decisions related to adaptation.     

Clinical management of BRCA1 and BRCA2 mutation carriers

The cancer susceptibility genes BRCA1 and BRCA2 appear to be responsible for virtually all hereditary breast ovarian families, and a smaller subset of hereditary site-specific breast cancer families. Fortunately, effective strategies have been developed to reduce the risk for the development of breast and ovarian cancer in women with BRCA1/2 mutations, making genetic testing for these mutations an important part of the management at women with a strong family history of these diseases. Here, we review the current evidence for risk reduction strategies and outline future research directions.     

Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer

Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one’s mutation positive status (OR 2.9, p < 0.001) and having a mother and/or sister who died from ovarian cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.     

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.