Rachel Nusbaum

Randomized Noninferiority Trial of Telephone Versus In-Person Genetic Counseling for Hereditary Breast and Ovarian Cancer

PURPOSE Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery. PATIENTS AND METHODS Participants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC participants received in-person pre- and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC. RESULTS TC was noninferior to UC on all primary outcomes. At 2 weeks after pretest counseling, knowledge (d = 0.03; lower bound of 97.5% CI, -0.61), perceived stress (d = -0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d = -0.16; lower bound of 97.5% CI, -0.70) had group differences and confidence intervals that did not cross their 1-point noninferiority limits. Decision conflict (d = 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d = -1.6; upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit. Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of

A Qualitative Description of Receiving a Diagnosis of Clefting in the Prenatal or Postnatal Period

114 per patient. CONCLUSION Genetic counseling can be effectively and efficiently delivered via telephone to increase access and decrease costs.

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing

This study investigated the experience of receiving a diagnosis of clefting in the prenatal or postnatal period. Open-ended interviews were conducted with 20 parents of children with cleft lip with or without cleft palate. Interviews were transcribed and analyzed using a qualitative descriptive approach with an emphasis on thematic analysis. Common themes emerged from participants’ responses regarding the delivery of the diagnosis, preparation for the birth of their child, advantages and disadvantages of prenatal diagnosis, use of the Internet, views on abortion and genetic testing, among other issues. All participants in the prenatal group indicated they were satisfied they learned of the cleft before the birth of their child. Some participants in the postnatal group would rather have received the diagnosis prenatally, while others were content with learning of the diagnosis in the delivery room. Greater awareness of the parental experience of the timing of receiving a cleft diagnosis may assist health care professionals in providing care for these families.

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

Purpose:Germ-line testing for panels of cancer genes using next-generation sequencing is becoming more common in clinical care. We report our experience as a clinical laboratory testing both well-established, high-risk cancer genes (e.g., BRCA1/2, MLH1, MSH2) as well as more recently identified cancer genes (e.g., PALB2, BRIP1), many of which have increased but less well-defined penetrance.Methods:Clinical genetic testing was performed on over 10,000 consecutive cases referred for evaluation of germ-line cancer genes, and results were analyzed for frequency of pathogenic or likely pathogenic variants, and were stratified by testing panel, gene, and clinical history.Results:Overall, a molecular diagnosis was made in 9.0% of patients tested, with the highest yield in the Lynch syndrome/colorectal cancer panel. In patients with breast, ovarian, or colon/stomach cancer, positive yields were 9.7, 13.4, and 14.8%, respectively. Approximately half of the pathogenic variants identified in patients with breast or ovarian cancer were in genes other than BRCA1/2.Conclusion:The high frequency of positive results in a wide range of cancer genes, including those of high penetrance and with clinical care guidelines, underscores both the genetic heterogeneity of hereditary cancer and the usefulness of multigene panels over genetic tests of one or two genes.Genet Med 18 8, 823–832.

Management Updates for Women with a BRCA1 or BRCA2 Mutation

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.

Disparities in uptake of BRCA1/2 genetic testing in a randomized trial of telephone counseling

In most cases of families with breast and ovarian cancer, the pattern of cancers in the family can be attributed to mutations in the BRCA1 and BRCA2 genes. Genetic testing for these cancer susceptibility genes typically takes place in the context of comprehensive genetic counseling. Strategies have been developed for the medical management of women at high risk of developing breast cancer, including options for screening and prophylactic surgery. BRCA1 and BRCA2 carriers are recommended to undergo prophylactic bilateral salpingo-oophorectomy by age 35–40 years or when childbearing is complete. This surgery significantly reduces the risk of ovarian cancer and also reduces the risk of breast cancer when performed in premenopausal mutation carriers. For breast cancer management, BRCA1 and BRCA2 carriers are offered the options of increased surveillance, with or without chemoprevention, or prophylactic surgery. Currently, BRCA carrier status is not used as an independent prognostic factor regarding systemic treatment options.

Susceptibility to Breast Cancer: Hereditary Syndromes and Low Penetrance Genes

Purpose: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:Methods include multivariable logistic regression and interaction analyses.Results: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.Conclusion: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.

Intentions for Bilateral Mastectomy Among Newly Diagnosed Breast Cancer Patients

Several genes are associated with hereditary susceptibility to breast cancer. Most notably these include BRCA1 and BRCA2; however, other less common gene mutations which confer elevated breast cancer risk are associated with Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, ataxia-telangiectasia heterozygosity and hereditary diffuse gastric cancer. In this article we highlight the genetic epidemiology, gene function, genotype-phenotype correlations, cancer risks and clinicopathologic findings for the cancer susceptibility genes related to these syndromes. We also examine genes, such as CHEK2, which confer a lower penetrance for breast cancer in comparison to these highly penetrant genes.

Intentions for risk‐reducing surgery among high‐risk women referred for BRCA1/BRCA2 genetic counseling

Recent trends suggest that bilateral mastectomy (BM) is on the rise among women diagnosed with unilateral breast cancer. Few studies have investigated the factors associated with the decision to have more aggressive surgery among young, high risk patients.

Discussing race-related limitations of genomic testing for colon cancer risk: implications for education and counseling.

Genetic testing for breast and ovarian cancer susceptibility is now part of routine clinical practice. Although rates of risk‐reducing surgery following genetic testing have been increasing, little is known about attitudes toward risk‐reducing surgery in women prior to genetic counseling and testing. This study examines correlates of patient intentions to undergo risk‐reducing mastectomy (RRM) and risk‐reducing oophorectomy (RRO).