Tiffani A. DeMarco

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

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.

Breast and ovarian cancer screening practices in healthy women with a strong family history of breast or ovarian cancer.

Studies in women with a family history of cancer demonstrate a wide variability in the uptake of cancer screening measures. Little data exist regarding the breast and ovarian cancer screening practices of women who are members of hereditary breast cancer families. In order to address this issue, we examined the screening behaviors and the determinants of screening in a clinic based group of 216 women with a strong family history of breast or ovarian cancer who were participating in a free genetic counseling and testing research program. At baseline, prior to obtaining genetic counseling or testing, 50% of women ages 30–39, 83% of those age 40–49, 69% of those 50–64, and 53% of those ≥65 reported having a mammogram in the prior year. Adherence to mammography recommendations was correlated with age, number of relatives with breast cancer, and income. Twenty percent of participants had at least one CA-125 performed and 31% had ever obtained a screening ultrasound. Having at least one relative with ovarian cancer was very strongly associated with ovarian cancer screening [OR = 12.3, 95% CI = 4.6–33 for CA-125; OR = 4.9, 95% CI = 2.4,10.1 for ultrasound]. No association between cancer worries/distress and either breast or ovarian cancer screening was found. In conclusion, the breast and ovarian screening uptake in healthy women from hereditary breast cancer families is suboptimal, even for women over age 50, for whom annual mammography is clearly indicated. These findings indicate a need for better education about screening guidelines for high-risk women.

Utilization of BRCA1/BRCA2 Mutation Testing in Newly Diagnosed Breast Cancer Patients

Background: Among newly diagnosed breast cancer patients who are at risk for carrying a BRCA1 or BRCA2 mutation, knowledge of mutation status can influence local breast cancer treatment decisions. Thus, genetic testing at the time of diagnosis is increasingly considered an option for such patients. In this study, we evaluated factors associated with the decision to undergo BRCA1/BRCA2 gene testing at the time of initial breast cancer diagnosis. Methods: Participants were newly diagnosed breast cancer patients who had not yet received definitive local breast cancer treatment and who had a family history consistent with hereditary breast cancer. Participants were offered genetic counseling and BRCA1/BRCA2 testing with results in 2 to 3 weeks. Results: Of 231 patients who referred to the study, 20 (9%) declined the baseline interview, 34 (15%) completed a baseline interview but declined genetic testing, and 177 (76%) underwent BRCA1/BRCA2 testing. Physician recommendation for BRCA1/BRCA2 testing and indecision about definitive local treatment were both associated with undergoing testing. Among patients who were tested, 38 (21%) proceeded with definitive local treatment before receiving test results. Delay in the availability of test results and low levels of anxiety were associated with the decision to proceed with definitive local treatment before receiving test results. Conclusions: These results suggest that if rapid testing is available and genetic referrals are made for appropriate patients, a high proportion are likely to opt for such testing. In particular, patients who have not yet reached a decision about definitive local treatment may benefit from a genetic referral.

Quality of Life After Contralateral Prophylactic Mastectomy in Newly Diagnosed High-Risk Breast Cancer Patients Who Underwent BRCA1/2 Gene Testing

PURPOSE Recent studies indicate that high-risk breast cancer patients (ie, women who carry mutations in BRCA1/2 genes) who opt for contralateral prophylactic mastectomy (CPM) have a substantially reduced risk of developing contralateral breast cancer. However, the immediate and long-term impact of this decision on womens quality of life and psychosocial functioning is largely unknown. In this study, we compared the impact of BRCA1/2 genetic test result and CPM on these outcomes among newly diagnosed breast cancer patients who opted for CPM at the time of their definitive surgical treatment versus patients who did not. PATIENTS AND METHODS Participants were 149 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. We measured self-reported quality of life, cancer-specific distress, and genetic testing-specific distress using standardized instruments before receipt of genetic test results and again 1 and 12 months later. RESULTS Compared with patients who chose breast conservation or unilateral mastectomy, those who chose mastectomy of the affected breast and CPM of the unaffected breast did not report diminished quality of life or elevated distress. CONCLUSION With respect to quality of life and distress, patients who choose CPM fare as well as those who do not in the first year after surgery.

Randomized Trial of a Decision Aid for BRCA1/BRCA2 Mutation Carriers: Impact on Measures of Decision Making and Satisfaction

OBJECTIVE Genetic testing is increasingly part of routine clinical care for women with a family history of breast cancer. Given their substantially elevated risk for breast cancer, BRCA1/BRCA2 mutation carriers must make the difficult decision whether or not to opt for risk reducing mastectomy. To help BRCA1/2 carriers make this decision, the authors developed a computer-based interactive decision aid that was tested against usual care in a randomized controlled trial. DESIGN After the completion of genetic counseling, 214 female (aged 21-75) BRCA1/BRCA2 mutation carriers were randomized to Usual Care (UC; N = 114) or Usual Care plus Decision Aid (DA; N = 100) arms. UC participants received no additional intervention. DA participants were sent the CD-ROM DA to view at home. MAIN OUTCOME MEASURES The authors measured final management decision, decisional conflict, decisional satisfaction, and receipt of risk reducing mastectomy at 1-, 6-, and 12-months postrandomization. RESULTS Longitudinal analyses revealed that the DA was effective among carriers who were initially undecided about how to manage their breast cancer risk. Within this group, the DA led to an increased likelihood of reaching a management decision (OR = 3.09, 95% CI = 1.62, 5.90; p < .001), decreased decisional conflict (B = -.46, z = -3.1, p <002), and increased satisfaction (B = .27, z = 3.1, p = .002) compared to UC. Among carriers who had already made a management decision by the time of randomization, the DA had no benefit relative to UC. CONCLUSION These results demonstrate that BRCA1/BRCA2 mutation carriers who are having difficulty making a breast cancer risk management decision can benefit from adjunct decision support.

Patient Satisfaction with Cancer Genetic Counseling: A Psychometric Analysis of the Genetic Counseling Satisfaction Scale

Satisfaction is an important patient reported outcome of genetic counseling, as it is one of the elements used by professional organizations and healthcare accrediting bodies to determine the quality of professional work. However, empirical research on patient satisfaction with genetic counseling has been limited, partly due to the lack of standardized measures available to assess this construct. The purpose of this study was to conduct a psychometric analysis of a new satisfaction measure, the Genetic Counseling Satisfaction Scale (GCSS), within a sample of women participating in a no-cost cancer genetic counseling and testing program. The sample consisted of 61 women undergoing counseling and testing for hereditary breast-ovarian cancer risk (BRCA1/2 testing) who completed the GCSS following pretest counseling. The results suggest that the GCSS was reliable (Cronbachs coefficient alpha = 0.90) and that participants were highly satisfied with the care they received. In addition, there were no differences in satisfaction between cancer genetic counseling and prenatal counseling participants (based on preexisting norms), and satisfaction did not vary by sociodemographic characteristics. Implications and recommendations are discussed.

Tolerance for uncertainty and perceived risk among women receiving uninformative BRCA1/2 test results†

Women who receive uninformative BRCA1/2 genetic test results face ongoing uncertainty about their future cancer risks. This article prospectively examined the influence of intolerance for uncertainty and perceived breast cancer risk on psychological distress following the receipt of uninformative BRCA1/2 test results. Sixty‐four women who received uninformative BRCA1/2 mutation test results completed measures of Intolerance for Uncertainty, perceived breast cancer risk, and measures of cancer‐related, genetic testing, and general distress. Cancer‐related (ΔR2 = 0.18, P ≤ 0.001), general (ΔR2 = 0.04, P ≤ 0.05), and genetic testing distress (ΔR2 = 0.12, P ≤ 0.01) were associated with intolerance for uncertainty at 1 month post‐disclosure. The interaction of intolerance for uncertainty and breast cancer perceived risk predicted cancer‐related (ΔR2 = 0.10, P ≤ 0.001) and genetic testing distress (ΔR2 = 0.09, P ≤ 0.01) at 6 months post‐disclosure. Distress was highest among patients with highest perceived risk and intolerance for uncertainty, suggesting that those who have difficulty coping with their ambiguous risk are at risk for long‐term distress. The clinical and research implications of these results are discussed.

Telephone genetic counseling for high-risk women undergoing BRCA1 and BRCA2 testing: rationale and development of a randomized controlled trial.

Genetic counseling and testing, particularly for adult onset conditions, has become increasingly available over the last decade, and it is expected that this trend will continue as additional genes are identified and as such testing diffuses into mainstream clinical care. To meet the increased demand for services, it will become necessary to explore alternative avenues to traditional face-to-face genetic counseling. One such modality is the use of telephone genetic counseling (TGC), which is easy to implement and still allows for comprehensive service delivery. Although TGC has been used with increased frequency, there is a paucity of data about its effectiveness and impact on important patient outcomes. This paper provides an overview of the evolution of telephone counseling in nongenetics and genetics settings. The rationale and aims of the largest randomized clinical trial to be performed with this mode of counseling in the context of cancer susceptibility testing for mutations in the BRCA1 and BRCA2 genes are also explained. In addition, procedural aspects of the genetic counseling intervention and the novel tools developed to facilitate this process and to ensure adequate counselor training and quality assurance are described.

Longitudinal Changes in Patient Distress following Interactive Decision Aid Use among BRCA1/2 Carriers: A Randomized Trial

Background. Increasingly, women with a strong family history of breast cancer are seeking genetic testing as a starting point to making significant decisions regarding management of their cancer risks. Individuals who are found to be carriers of a BRCA1 or BRCA2 mutation have a substantially elevated risk for breast cancer and are frequently faced with the decision of whether to undergo risk-reducing mastectomy. Objective. In order to provide BRCA1/2 carriers with ongoing decision support for breast cancer risk management, a computer-based interactive decision aid was developed and tested against usual care in a randomized controlled trial. Design. Following genetic counseling, 214 female (aged 21–75 years) BRCA1/2 mutation carriers were randomized to usual care (UC; n = 114) or usual care plus decision aid (DA; n = 100) arms. UC participants received no further intervention; DA participants were sent the CD-ROM–based decision aid to view at home. Main Outcome Measures. The authors measured general distress, cancer-specific distress, and genetic testing–specific distress at 1-, 6-, and 12-month follow-up time points postrandomization. Results. Longitudinal analyses revealed a significant longitudinal impact of the DA on cancer-specific distress (B = 5.67, z = 2.81, P = 0.005), which varied over time (DA group by time; B = −2.19, z = −2.47, P = 0.01), and on genetic testing–specific distress (B = 5.55, z = 2.46, P = 0.01), which also varied over time (DA group by time; B = −2.46, z = −2.51, P = 0.01). Individuals randomized to UC reported significantly decreased distress in the month following randomization, whereas individuals randomized to the DA maintained their postdisclosure distress over the short term. By 12 months, the overall decrease in distress between the 2 groups was similar. Conclusion. This report provides new insight into the long-term longitudinal effects of DAs.

Women’s Satisfaction with Genetic Counseling for Hereditary Breast-Ovarian Cancer: Psychological Aspects

Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast‐ovarian cancer at some point during their lifetimes. For these women, obtaining pre‐test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly report being highly satisfied with their cancer genetic counseling experience, even if the information learned through testing suggests they are at increased cancer risk. This occurrence raises an interesting question, namely, what are the psychological aspects of satisfaction with genetic counseling for hereditary breast‐ovarian cancer in women? To answer this question, we administered the Genetic Counseling Satisfaction Scale (GCSS) to a convenience sample of 61 women participating in BRCA1/2 pretest genetic counseling, and re‐administered the GCSS to approximately one‐third of these women at disclosure. Available psychological data included personality, distress, and family functioning. In bivariate analyses, optimism and family functioning were positively associated with pretest satisfaction. With respect to satisfaction at disclosure, general and cancer‐specific distress were negatively associated with satisfaction. Our findings suggest that psychological aspects of satisfaction with cancer genetic counseling vary, with individual differences and family functioning playing a role at pretest, and distress playing a role at disclosure. The implications for future research and clinical practice are discussed.