Most literature describing pharmacogenetic implementations are within academic medical centers and use single‐gene tests. Our objective was to describe the results and lessons learned from a ...multisite pharmacogenetic pilot that utilized panel‐based testing in academic and nonacademic settings. This was a retrospective analysis of 667 patients from a pilot in 4 perioperative and 5 outpatient cardiology clinics. Recommendations related to 12 genes and 65 drugs were classified as actionable or not actionable. They were ascertained from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines and US Food and Drug Administration (FDA) labeling. Patients displayed a high prevalence of actionable results (88%, 99%) and use of medications (28%, 46%) with FDA or CPIC recommendations, respectively. Sixteen percent of patients had an actionable result for a current medication per CPIC compared with 5% per FDA labeling. A systematic approach by a health system may be beneficial given the quantity and diversity of patients affected.
As genetic counseling and testing become more fully integrated into clinical care, alternative delivery models are increasingly prominent. This study examines predictors of genetic testing for ...hereditary breast/ovarian cancer among high-risk women in a randomized trial of in-person versus telephone-based genetic counseling.
Methods include multivariable logistic regression and interaction analyses.
Of the 669 participants, 600 completed counseling and 523 received test results. As previously reported, participants randomized to telephone counseling were significantly less likely to be tested. In intention-to-treat analyses, completion of counseling and testing was associated with: race/ethnicity (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.20-3.20), perceived stress (OR = 0.89, 95% CI: 0.81-0.98), knowledge (OR = 1.12, 95% CI: 1.02-1.23), and randomization group (OR = 1.48, 95% CI: 1.01-2.16). Further, race/ethnicity moderated the association between randomization group and testing; minority women receiving telephone counseling were least likely to complete testing.
Evidence for logistical and communication-based explanations for this interaction is presented. The overall increased access made possible with telephone genetic counseling should be considered in light of the possibility that this may also lead to lower rates of testing among high-risk minority women. Additional care should be taken to assess and address potential barriers when services are delivered by telephone.Genet Med 17 6, 467-475.
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.
Objective
As germline genetic referral becomes increasingly routine as part of the care of newly diagnosed breast cancer patients, it is important to understand the psychosocial impact of genetic ...counseling at the time of diagnosis. We examined the psychosocial and quality of life (QOL) impact of providing proactive rapid genetic counseling and testing (RGCT) in the immediate aftermath of a breast cancer diagnosis.
Methods
We randomized 330 patients in a 2:1 ratio to proactive rapid genetic counseling (RGCT; N = 222) versus usual care (UC; N = 108). Participants completed a baseline telephone survey before randomization and definitive surgery and a follow‐up survey at 1‐month post‐randomization. We evaluated the impact of RGCT versus UC on breast cancer genetic knowledge, distress, QOL, and decisional conflict. Given that 43% of UC participants and 86% of RGCT participants completed genetic counseling prior to the 1‐month assessment, we also evaluated the impact of genetic counseling participation over and above group assignment.
Results
The RGCT intervention led to increased breast cancer genetic knowledge relative to UC but did not differentially impact other study outcomes. Across groups patients who participated in genetic counseling had significantly increased knowledge and improved QOL compared to those who did not participate in genetic counseling.
Conclusions
While prior research has documented the impact of genetic counseling and testing on surgical decisions, these results confirm that participation in genetic counseling at the time of diagnosis can yield improvements in knowledge and QOL in the short‐term.
To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the ...relevance of other susceptibility genes in familial breast and ovarian cancer.
Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing.
Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown.
BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.
To evaluate the effect of pharmacogenomics (PGx) education for pharmacists.
Three-part weekly webinar series occurred in 2021. Pharmacists were assessed on their PGx knowledge at baseline and after ...each webinar. The primary end point was a change in the percent of correct responses between the baseline and week 1 assessment. Secondary end points included change in knowledge at weeks 4-8 and change in self-efficacy.
In total, 19 of 58 participants were eligible for the primary analysis, which showed an average improvement of 37% (p < 0.0001). Knowledge remained consistent between week 1 and weeks 4-8. Average self-efficacy increased (p < 0.0001) and was maintained at weeks 4-8.
The PGx webinar series resulted in a lasting improvement in PGx knowledge and self-efficacy.
Despite the disproportionate underuse of genetic counseling and testing for
BRCA1/2
(
BRCA
)-associated hereditary breast and ovarian cancer (HBOC) risk among Latinas, little is known about the ...associated barriers and facilitators. We conducted in-depth qualitative interviews with 20 at-risk Latina women from diverse backgrounds. Eligible women were diagnosed with breast cancer <50 years, with or without a family history of breast and/or ovarian cancer (>1 first-degree relative diagnosed <50 years). All interviews were conducted in Spanish, audio recorded, transcribed, and translated into English. Two bilingual coders used thematic analyses to identify 7 main themes. Results revealed very low levels of awareness and knowledge about HBOC and
BRCA
genetic counseling. Interestingly, for most Latinas, competing life demands and cultural concerns (
fatalismo
and
destino
) did not strongly influence personal beliefs about genetic counseling. In addition, older women were equally as interested in education, cancer prevention, and
BRCA
genetic counseling as younger women. These findings suggest that Latinas, regardless of age, increasingly acknowledge and prioritize their own health. Women reported their main motivator to undergo counseling was concern about family members’ cancer risks. Main barriers included financial and insurance concerns, and lack of awareness about genetic services. Investigating the beliefs and attitudes of diverse populations of Latinas at risk for HBOC reveals logistical barriers to
BRCA
genetic counseling uptake within this under-represented community. Efforts are needed to provide at-risk Latina breast cancer survivors’ knowledge of and access to genetic counseling and testing based on risk status and Latinas’ increasing responsiveness and uptake of these services.
Telegenetics has become the predominant mode of cancer genetic counseling during the COVID-19 pandemic. We sought to identify potential patient-level contraindicators for telegenetic genetic ...counseling.
We analyzed post-counseling (pre-result disclosure) follow-up data from a randomized noninferiority trial of a telephone genetic counseling versus usual care genetic counseling. Among 669 randomized participants, 600 completed pre-test counseling and 568 completed a 2-week follow-up assessment before receiving test results. In this analysis, we focused on genetic counseling outcomes (knowledge, decisional conflict, and distress). In multivariate models controlling for bivariate predictors of these outcomes, we tested our a priori hypotheses that pre-counseling numeracy, perceived stress, and race/ethnicity would moderate the outcomes of telephone genetic counseling versus usual care.
Only numeracy significantly moderated associations between mode of genetic counseling and outcomes. Higher numeracy was associated with higher post-counseling knowledge following telephone genetic counseling (
< 0.001), but not usual care (
= 0.450). Higher numeracy was also associated with lower distress following telephone genetic counseling (
= 0.009) but not usual care (
= 0.16). Neither perceived stress nor race/ethnicity exhibited differential impacts on telephone genetic counseling versus usual care (
s > 0.20).
Although high numeracy was associated with higher levels of knowledge following telegenetic counseling, we did not identify any clinically significant patient-level contraindicators for telegenetic counseling. These results lend further confidence to the broad use of telegenetics.
Germline genetic testing is recommended for men with metastatic or high-risk prostate cancer to inform treatment and risk management for other cancers and inform genetic testing in at-risk relatives. ...However, relatively few patients with prostate cancer undergo genetic testing. Given the low rate of testing and increasing demands on genetic service providers, strategies are needed that reduce barriers to testing while conserving genetic counseling resources. The primary goal of this study was to determine whether a proactive and streamlined "traceback" approach could yield increased genetic testing participation among prostate cancer survivors.
We randomized 107 survivors of metastatic and high-risk prostate cancer to streamlined testing (ST) versus enhanced usual care (EUC). ST participants were proactively provided with print genetic education materials and the option to proceed to genetic testing without pre-test genetic counseling. EUC participants were sent a letter from their physician advising them of their eligibility for genetic testing and recommending they schedule genetic counseling. The primary outcome was genetic testing participation. Secondary outcomes were distress, knowledge, decision satisfaction, and regret.
In the ST group, 41.5% of participants completed genetic testing compared with 27.8% in the EUC group. After adjusting for education and marital status, the odds of testing were more than twice as high for the ST group as for the EUC group (odds ratio, 2.57; 95% CI, 1.05-6.29). The groups did not differ on any of the psychosocial outcomes at the 3-month follow-up.
Proactive outreach paired with streamlined genetic testing delivery may be a safe, effective, and resource-efficient approach to facilitate traceback genetic testing in prostate cancer survivors.
Background and Objectives
Many newly diagnosed breast cancer patients do not receive genetic counseling and testing at the time of diagnosis. We examined predictors of genetic testing (GT) in this ...population.
Methods
Within a randomized controlled trial of proactive rapid genetic counseling and testing vs usual care, patients completed a baseline survey within 6 weeks of breast cancer diagnosis but before a definitive survey. We conducted a multinomial logistic regression to identify predictors of GT timing/uptake.
Results
Having discussed GT with a surgeon was a dominant predictor (χ2 (2, N = 320) = 70.13; P < .0001). Among those who discussed GT with a surgeon, patients who had made a final surgery decision were less likely to receive GT before surgery compared with postsurgically (OR odds ratio = 0.24; 95% confidence interval CI = 0.12‐0.49) or no testing (OR = 0.28; 95% CI = 0.14‐0.56). Older patients (OR = 0.95; 95% CI = 0.91‐0.99) and participants enrolled in New York/New Jersey (OR = 0.22; 95% CI = 0.07‐0.72) were less likely to be tested compared with receiving results before surgery. Those with higher perceived risk (OR = 1.02; 95% CI = 1.00‐1.03) were more likely to receive results before surgery than to not be tested.
Conclusions
This study highlights the role of patient‐physician communication about GT as well as patient‐level factors that predict presurgical GT.
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