Approximately 5% to 10% of newly diagnosed breast cancer patients carry a BRCA1 or BRCA2 mutation. Given these patients' high risk for contralateral breast cancer, bilateral mastectomy is ...increasingly considered a treatment option for newly diagnosed BRCA1/2 carriers. In the present study, we prospectively evaluated the impact on surgical decision-making of pretreatment genetic counseling and BRCA1/BRCA2 testing among breast cancer patients at high-risk for carrying a mutation.
Participants were 194 newly diagnosed breast cancer patients who had not yet received definitive surgical treatment and who had at least a 10% prior probability of carrying a BRCA1/2 mutation. Participants were offered free genetic counseling and rapid BRCA1/2 testing. Primary analyses focused on the impact of BRCA1/2 test result on subsequent breast cancer surgical treatment.
Forty-eight percent of patients who were found to carry a BRCA1/2 mutation chose bilateral mastectomy as their definitive breast cancer surgery. In contrast, 24% of patients in whom no mutation was detected and 4% of test decliners opted for bilateral mastectomy. Additional predictors of bilateral mastectomy included patients' self-reports of physician recommendations for BRCA1/2 testing and bilateral mastectomy.
This study highlights patient interest in and the technical feasibility of offering presurgery BRCA1/2 testing to high-risk patients. Most importantly, these results demonstrate that BRCA1/2 test results significantly affect patients' surgical decision-making. The availability of genetic counseling and testing could serve as a valuable aid to patient decision-making for newly diagnosed breast cancer patients at high-risk for carrying a mutation.
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 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.
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).
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.
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.
To assess physician recommendations about the use of tamoxifen in premenopausal BRCA1 and BRCA2 mutation carriers.
We mailed surveys to a stratified random sample of 1,286 physicians selected from ...the San Antonio Breast Cancer Symposium mailing list. Eligible participants were physicians whose practice consisted of >/= 10% breast cancer patients. Participants were asked to complete a three-part, 10-minute questionnaire. Demographics and responses to hypothetical patient vignettes were analyzed.
Of potentially eligible participants, 27% responded to the survey, and 260 participants were included in the final analysis. Physicians did not distinguish between BRCA1 and BRCA2 status in making recommendations about tamoxifen to breast cancer patients; however, in an unaffected woman, they were more likely to recommend tamoxifen to a BRCA2 mutation carrier than to a BRCA1 mutation carrier (73% v 57%; P <.0001). In newly diagnosed breast cancer patients, physicians were much more likely to recommend tamoxifen to an estrogen receptor (ER)-positive mutation carrier versus an ER-negative carrier (94% v 27%; P <.0001). When the mutation carrier was diagnosed 10 years ago, physicians were still much more likely to recommend tamoxifen if the tumor was ER-positive versus ER-negative (79% v 35%; P <.0001).
Physicians' recommendations about tamoxifen use in mutation carriers with a history of breast cancer seem to be heavily dependent on ER status. This finding suggests that among mutation carriers, physicians are influenced by adjuvant treatment guidelines more so than the potential role that tamoxifen might play in the reduction of risk for contralateral breast cancer.
Numerous studies have documented the short-term impact of BRCA1/BRCA2 (BRCA1/2) testing; however, little research has examined the long-term impact of testing. We conducted the first long-term ...prospective study of psychosocial outcomes in a U.S. sample of women who had BRCA1/2 testing.
Participants were 464 women who underwent genetic testing for BRCA1/2 mutations. Prior to testing, we measured sociodemographics, clinical variables, and cancer specific and general distress. At long-term follow-up (Median = 5.0 years; Range = 3.4-9.1 years), we assessed cancer-specific and genetic testing distress, perceived stress, and perceived cancer risk. We evaluated the impact of BRCA1/2 test result and risk-reducing surgery on long-term psychosocial outcomes.
Among participants who had been affected with breast or ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.41, P < 0.0001), uncertainty (β = 0.18, P < 0.0001), and perceived stress (β = 0.17, P = 0.005) compared with women who received negative (i.e., uninformative) results. Among women unaffected with breast/ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.39, P < 0.0001) and lower positive testing experiences (β = 0.25, P = 0.008) than women with negative results. Receipt of risk-reducing surgery was associated with lower perceived cancer risk (P < 0.0001).
In this first prospective long-term study in a U.S. sample, we found modestly increased distress in BRCA1/2 carriers compared with women who received uninformative or negative test results. Despite this modest increase in distress, we found no evidence of clinically significant dysfunction.
Although a positive BRCA1/2 result remains salient among carriers years after testing, testing does not seem to impact long-term psychologic dysfunction.
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.
The objectives of this observational study were to describe the associations between cultural beliefs and values and participation in genetic risk assessment and testing among African American women ...at high risk for having a BRCA1 or BRCA2 (BRCA1/2) gene alteration. Subjects were 28 high-risk women who self-referred to a genetic counseling and testing research program. Overall, 61% subjects received BRCA1/2 test results and 39% declined. Mean levels of fatalistic beliefs about cancer and future temporal orientation were higher among test acceptors relative to decliners. Sociodemographic factors were not associated with test acceptance; however, rates of test acceptance were lower among women with greater perceptions of familial interdependence (41% versus 91%,
P=0.02). The results of this study suggest that cultural beliefs and values may influence genetic testing decisions among African American women.
Despite the potential importance of communication about genetic testing between test participants and their significant others, little is known about social support and communication between women ...undergoing BRCA1 and BRCA2 testing and their partners.
The aims of this longitudinal study were to examine communication about genetic testing during and following testing and to evaluate whether communication is associated with psychological distress reported by test participants and their partners.
Participants were 153 women who were undergoing genetic testing and 118 partners of women undergoing testing. Relationship communication and distress were evaluated at the time of pretest education and 6 months postdisclosure.
Overall, the decision to undergo testing was discussed by the majority of test participants and partners, and most couples felt their partners were supportive. Most women disclosed their results to their partners. Longitudinal analyses suggested that less support and protective buffering were associated with greater distress 6 months postdisclosure among test participants, whereas lower comfort in sharing concerns and partner support were associated with lower distress 6 months postdisclosure among partners.
The results of this study suggest that the majority of couples respond supportively during the test experience, but for a small subset of couples the process can strain the relationship. Partner support during this process is important, particularly for test participants dealing with an uninformative test result.
To examine the relation between dopamine (DA) D2 receptor-specific binding and personality, we assessed the relation between DA D2 binding and the NEO Personality Inventory-Revised (NEO PI-R).
...Previous studies have demonstrated a relation between DA D2 receptor-specific binding and a personality trait involving personal detachment as defined by the Karolinska Scales of Personality: A subsequent study using a different measure of personal detachment failed to replicate this finding, suggesting that metric properties of the personality scale may be important. To further examine this issue, we assessed the relation between DA D2 binding and a third personality measure, the NEO PI-R.
Eighteen adult subjects completed the NEO PI-R and participated in an 11C-raclopride positron emission tomography study to quantify striatal DA D2 receptor binding.
We did not find a significant relation between binding and detachment-like traits on the NEO PI-R; however, we found a significant relation between DA D2 receptor binding and the NEO PI-R personality facet of Depression (r = 0.75, p <0.0001).
The results fail to replicate the findings of previous studies reporting an association between DA D2 receptor density and personal detachment, suggesting that the relation is relatively specific to the trait defined by the Karolinska Scales of Personality. The relation between a nonclinical personality trait of depression and DA D2 binding, if replicated, may help to elucidate the role of dopamine in depression.
PDF
