Does the choice of platinum doublet matter? A study to evaluate the impact of platinum doublet choice for treatment of platinum-sensitive ovarian cancer recurrence on the development of future PARP inhibitor and platinum resistance.

OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non­platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.

A Video Intervention to Improve Patient Understanding of Tumor Genomic Testing in Patients with Cancer.

Background: Tumor genomic testing (TGT) has become standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is variable or frequently omitted. The purpose of this study was to evaluate the impact of a concise (3-4 minute) video for patient education prior to TGT. Methods: Based on a quality improvement cycle, an animated video was created to be applicable to any cancer type, incorporating culturally diverse images, available in English and Spanish. Patients undergoing standard-of care TGT were enrolled at a tertiary academic institution and completed validated survey instruments immediately prior to video viewing (T1) and immediately post-viewing (T2). Instruments included: 1) 10-question objective genomic knowledge/understanding; 2) 10-question video message-specific knowledge/recall; 3) 11-question Trust in Physician/Provider; 4) attitudes regarding TGT. The primary objective was change in outcomes from before to after the video was assessed with Wilcoxon signed rank test. Results: From April 2022 to May 2023, a total of 150 participants were enrolled (MBC n=53, LC n=38, OC n=59). For the primary endpoint, there was a significant increase in video message-specific knowledge (median 10 point increase; p<0.0001) with no significant change in genomic knowledge/understanding (p=0.89) or Trust in Physician/Provider (p=0.59). Results for five questions significantly improved, including the likelihood of TGT impact on treatment decision, incidental germline findings, and cost of testing. Improvement in video message-specific knowledge was consistent across demographic groups, including age, income, and education. Individuals with less educational attainment had had greater improvement from before to after video viewing. Conclusions: A concise, 3-4 minute, broadly applicable video incorporating culturally diverse images administered prior to TGT significantly improved video message-specific knowledge across all demographic groups. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice. Clinical Trial Registration: ClinicalTrials.gov NCT05215769.

Genetic counseling and testing for females at elevated risk for breast cancer: Protocol for the randomized controlled trial of the Know Your Risk intervention.

BACKGROUND: Genetic counseling and testing have an important role in the care of patients at elevated risk for breast cancer. However, conventional pre- and post-test genetic counseling is labor and time intensive, less accessible for patients living outside major urban centers, and impractical on a large scale. A patient-driven approach to genetic counseling and testing may increase access, improve patients' experiences, affect efficiency of clinical practice, and help meet workforce demand. The objective of this 2-arm randomized controlled trial is to determine the efficacy of Know Your Risk (KYR), a genetic counseling patient preference intervention. METHODS: Females (n = 1000) at elevated risk (>20% lifetime) for breast cancer will be randomized to the KYR intervention or conventional genetic counseling. The study will provide comprehensive assessment of breast cancer risk by multigene panel testing and validated polygenic risk score. Primary outcome is adherence to National Comprehensive Cancer Network guidelines for a clinical encounter every 6-12 months and an annual mammogram (breast MRI if recommended) determined by medical record review. Secondary outcomes include adherence to other recommended cancer screening tests determined by medical record review and changes in breast cancer knowledge, perception of risk, post-test/counseling distress, and satisfaction with counseling by completion of three surveys during the study. Study aims will be evaluated for non-inferiority of the KYR intervention compared to conventional genetic counseling. CONCLUSION: If efficacious, the KYR intervention has the potential to improve patients' experience and may change how genetic counseling is delivered, inform best practices, and reduce workforce burden. TRIAL REGISTRATION: ClinicalTrials.govNCT05325151.

Recurrence rate in early-stage epithelial ovarian cancer: Is there a role for upfront maintenance with PARP inhibitors in stages I and II?

Objective: To determine the recurrence rate and survival among early-stage epithelial ovarian cancer cases considering homologous recombination deficiency (HRD) status. Methods: Single institution retrospective study of stage I/II EOC patients from 2017 to 2020. HRD was defined as evidence of germline or somatic BRCA mutation, or loss of heterozygosity (LOH)/genomic instability (GIS) as determined by companion diagnostic tests. Kaplan-Meier analyses were performed. Results: 89 stage I/II cases were included. 4/89 (4.5%) had a germline BRCA1/2 mutation, 8 (9%) were germline negative but had a somatic BRCA mutation, and 8 (9%) were BRCA wild-type but had evidence of LOH/GIS on somatic testing; these 20/89 (22%) cases comprised the HRD group. The remaining tumors were confirmed homologous recombination proficient (HRP, 35/89, 39%) or homologous recombination unknown (HRU, 34/89, 38%). The overall recurrence rate was 33/89 (37%). There were more recurrences among HRD cases (14/20, 70%) compared to HRP/HRU cases (19/69, 27.5%, p = 0.0012). Median Recurrence-Free Survival (RFS) was 35 months for HRD cases and 225 months for HRP/HRU cases (p = 0.001). At 2 years, there were 60% HRD cases and 88% HRP/HRU cases recurrence-free. At 5 years there were 29% HRD and 69% HRP/HRU cases recurrence-free (p = 0.001). Conclusions: Despite a high rate of complete surgical staging and six cycles of adjuvant chemotherapy, recurrence rate was high in this early-stage cohort. Higher recurrence rates were seen in the HRD group, however these data are likely biased by the clinical practice of tumor testing primarily at the time of recurrence rather than the upfront setting. RFS was significantly lower for HRD cases.

BRCAShare-Assessment of an animated digital message for intrafamilial communication of pathogenic variant positive test results: A feasibility study.

While genetic testing for hereditary breast and ovarian cancer syndrome (HBOC) is well-established in the field of medicine, family members' uptake of cascade genetic testing for known familial pathogenic variants remains low. Probands often become responsible for initiating familial communication about their testing results, and barriers to communication may include difficulty in conveying information to relatives and a lack of communication resources for probands' use. In this study, we tested a two-minute animated digital message (ADM) intervention guided by the Health Belief Model (HBM) in an unselected sample to determine hypothetical individual perceptions of susceptibility and severity and behavioral intention to act on the information provided in the ADM. We recruited genetic testing naïve adults from the United States with no personal history of cancer through Amazon Mechanical Turk to participate in this study. Participants were presented a hypothetical scenario describing a relative's recent HBOC diagnosis, viewed the ADM, and answered a questionnaire assessing participants' perception of the HBM constructs in relation to the hypothetical scenario and participants' intentions to pursue cascade genetic testing, talk to a healthcare professional, or talk to family members after ADM viewing. Participants (n = 373) largely perceived HBOC as serious and believed that they could benefit from the information provided by genetic testing; 76% hypothetically intended to pursue genetic testing at a cost of $100 or less, and 90% intended to either pursue testing or talk to a healthcare provider or family members. This feasibility study in an unaffected population could mimic the experience of distant/less-engaged relatives in HBOC families after receiving unexpected information about cascade genetic testing. Most participants demonstrated behavioral intention toward cascade testing, at a rate higher than literature would suggest is typical in high-risk families, indicating that a theory-supported, simple to use intervention may be useful in clinical practice.

The risks of cancer in older women with BRCA pathogenic variants: How far have we come?

BACKGROUND: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. METHODS: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow-up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow-up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan-Meier method. RESULTS: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk-reducing mastectomy and bilateral salpingo-oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. CONCLUSION: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately.

Development of a web-based, theory-guided narrative intervention for women at elevated risk for breast cancer.

OBJECTIVE: To describe the development of a web-based, theory-guided narrative intervention that replaces conventional pre-test genetic counseling for women at elevated breast cancer risk. METHODS: We used an iterative process that was guided by health behavior theory and feedback from multiple stakeholder groups including: 1) content input from genetic experts; 2) study team input; 3) review of video storyboards, video example, study logo, recruitment materials, post-test patient preference counseling survey, and additional study surveys; 4) video series development; and 5) intervention review and finalization of study-related materials. RESULTS: The intervention is patient-centered providing convenience and an opportunity for an individual's preferences for post-test counseling delivery. The intervention's efficacy is being determined in a randomized controlled trial compared to conventional genetic counseling for adherence to recommended guidelines and changes in knowledge, perception of breast cancer risk, breast cancer-specific worry, and satisfaction with counseling. CONCLUSION: If efficacious, the intervention may improve the delivery of the genetic testing and counseling process, inform best practices, and reduce the genetic counseling workforce burden. PRACTICE IMPLICATIONS: The developed intervention has the potential to improve the genetic testing and counseling experience for women at elevated risk for breast cancer, inform best practices, and reduce genetic counseling workforce burden.

Patient Understanding of Tumor Genomic Testing: A Quality Improvement Effort.

PURPOSE: Tumor genomic testing (TGT) has become increasingly adopted as part of standard cancer care for many cancers. Despite national guidelines around patient education before TGT, available evidence suggests that most patients' understanding of genomics remains limited, particularly lower-income and minority patients, and most patients are not informed regarding potential incidental germline findings. METHODS: To investigate and address limitations in patient understanding of TGT results, a Plan-Do-Study-Act (PDSA) approach is being used to assess needs, identify opportunities for improvement, and implement approaches to optimize patient education. We reviewed published guidelines related to pre-TGT provider-patient education and to identify key points (Plan). A provider quality improvement survey was completed (Do), which highlighted inconsistency in pre-TGT discussion practice across providers and minimal discussion with patients regarding the possibility of incidental germline findings. RESULTS: Patient focus groups and interviews (N = 12 patients) were completed with coding of each transcript (Study), which revealed themes including trouble differentiating TGT from other forms of testing, yet understanding that results could tailor therapy. The integration of data across this initial PDSA cycle identified consistent themes and opportunities, which were incorporated into a patient-directed, concise animated video for pre-TGT education (Act), which will form the foundation of a subsequent PDSA cycle. The video addresses how TGT may/may not inform treatment, the process for TGT using existing tissue or liquid biopsy, insurance coverage, and the potential need for germline genetics follow-up because of incidental findings. CONCLUSION: This PDSA cycle reveals key gaps and opportunities for improvement in patient education before TGT.

Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal.

BACKGROUND: The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case-control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer. METHODS: A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer. RESULTS: In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34-0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87-1.70; P = 0.26). CONCLUSIONS: The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk. IMPACT: Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.

Hospital-based ovarian cancer patient traceback program results in minimal genetic testing uptake.

OBJECTIVE: To determine the feasibility of hospital-based genetic counseling and testing (GC/T) Traceback for Ovarian Cancer (OC) patients, as proposed by the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute. METHODS: Living patients with OC were sent a letter explaining the availability of guideline-supported GC/T for at least BRCA1/2 and surrogates of deceased patients were called on the telephone. Outcomes of contact attempts were systematically recorded and statistically described. RESULTS: 598 Traceback-eligible OC patients diagnosed from 2006 to 2016 were identified (163 presumed-living and 435 deceased). Two living patients called our office and scheduled an appointment for GC/T after receiving a letter. For surrogates of prior patients, successful contact occurred in 25% of call attempts. Fourteen individuals (2 living patients and 12 surrogates) underwent genetic counseling. Of those 14, 10 individuals consented to genetic testing and 5 followed through with sample collection. None of these individuals had pathogenic variants (PVs). When surrogate call notes were reviewed, 58% reflected positive responses to contact, however 42% were noted to have negative or indifferent responses, which were most common among spouses. Total time spent for hospital-based Traceback was 109 h. CONCLUSIONS: Overall, hospital-based Traceback via letter and telephone contact of surrogates is time-intensive and results in minimal uptake of GC/T. To practically execute this type of outreach program, health systems should consider collection of alternative contact information to allow for electronic communication of patient surrogates. Our study also underscores the importance of timely GC/T while patients are in active cancer care.

Risk assessment and genetic counseling for Lynch syndrome - Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.

Identifying individuals who have Lynch syndrome involves a complex diagnostic workup that includes taking a detailed family history and a combination of various tests such as immunohistochemistry and/or molecular which may be germline and/or somatic. The National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer have come together to publish this practice resource for the evaluation of Lynch syndrome. The purpose of this practice resource was to provide guidance and a testing algorithm for Lynch syndrome as well as recommendations on when to offer testing. This practice resource does not replace a consultation with a genetics professional. This practice resource includes explanations in support of this and a summary of background data. While this practice resource is not intended to serve as a review of Lynch syndrome, it includes a discussion of background information and cites a number of key publications which should be reviewed for a more in-depth understanding. This practice resource is intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses, and other healthcare providers who evaluate patients for Lynch syndrome.

Contraceptive use and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation.

Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52-0.75; P < 0.0001), which was driven by significant inverse associations with oral contraceptives (OR = 0.66; 95% CI 0.54-0.79; P < 0.0001) and contraceptive implants (OR = 0.30; 95% CI 0.12-0.73; P = 0.008). We observed a similar effect with use of injections (OR = 0.37; 95% CI 0.10-1.38; P = 0.14), but this did not achieve significance. No significant associations were observed between patterns of intrauterine device use and risk of ovarian cancer. Conclusions These findings support a protective effect of oral contraceptives and implants on risk of ovarian cancer among women with BRCA mutations. The possible protective effect of injections requires further evaluation.

Improving the quality of care for patients with advanced epithelial ovarian cancer: Program components, implementation barriers, and recommendations.

The high lethality of ovarian cancer in the United States and associated complexities of the patient journey across the cancer care continuum warrant an assessment of current practices and barriers to quality care in the United States. The objectives of this study were to identify and assess key components in the provision of high-quality care delivery for patients with ovarian cancer, identify challenges in the implementation of best practices, and develop corresponding quality-related recommendations to guide multidisciplinary ovarian cancer programs and practices. This multiphase ovarian cancer quality-care initiative was guided by a multidisciplinary expert steering committee, including gynecologic oncologists, pathologists, a genetic counselor, a nurse navigator, social workers, and cancer center administrators. Key partnerships were also established. A collaborative approach was adopted to develop comprehensive recommendations by identifying ideal quality-of-care program components in advanced epithelial ovarian cancer management. The core program components included: care coordination and patient education, prevention and screening, diagnosis and initial management, treatment planning, disease surveillance, equity in care, and quality of life. Quality-directed recommendations were developed across 7 core program components, with a focus on ensuring high-quality ovarian cancer care delivery for patients through improved patient education and engagement by addressing unmet medical and supportive care needs. Implementation challenges were described, and key recommendations to overcome barriers were provided. The recommendations emerging from this initiative can serve as a comprehensive resource guide for multidisciplinary cancer practices, providers, and other stakeholders working to provide quality-directed cancer care for patients diagnosed with ovarian cancer and their families.

The risks of breast and ovarian cancer associated with the Ashkenazi Jewish founder allele BRCA2 6174delT.

Approximately 1% of the Ashkenazi Jewish population carries the BRCA2 6174delT (c.5946del) pathogenic variant. It is important to have accurate knowledge of the risks of breast and ovarian cancer associated with this specific variant so that women may be counseled accordingly. In this prospective study, we estimated the risks of breast and ovarian cancer associated with the 6174delT variant compared with the risks for other pathogenic variants in the BRCA2 gene. The annual risk for developing breast cancer was significantly lower in 246 women who carried the 6174delT variant compared with 721 non-Jewish women who carried a variant at any other locus in BRCA2 (1.2% per year vs. 2.4% per year, p = 0.003). We estimated the cumulative risk of breast cancer from age 30 to 70 to be 39% for carriers of the BRCA2 6174delT variant and 61% for carriers of other BRCA2 variants. The annual risk for ovarian or fallopian tube cancer was 0.51% per year for the 233 women who carried the 6174delT variant compared to 0.22% per year for the 1128 carriers of other BRCA2 variants; the difference was not significant. Lower risks for breast cancer associated with 6174delT may not impact screening and prevention choices, however, the discussion should be based on accurate risk assessment.

Weight Gain and the Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers.

BACKGROUND: Weight gain and other anthropometric measures on the risk of ovarian cancer for women with BRCA mutations are not known. We conducted a prospective analysis of weight change since age 18, height, body mass index (BMI) at age 18, and current BMI and the risk of developing ovarian cancer among BRCA1 and BRCA2 mutation carriers. METHODS: In this prospective cohort study, height, weight, and weight at age 18 were collected at study enrollment. Weight was updated biennially. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for ovarian cancer. RESULTS: This study followed 4,340 women prospectively. There were 121 incident cases of ovarian cancer. Weight gain of more than 20 kg since age 18 was associated with a 2-fold increased risk of ovarian cancer, compared with women who maintained a stable weight (HR, 2.00; 95% CI, 1.13-3.54; P = 0.02). Current BMI of 26.5 kg/m2 or greater was associated with an increased risk of ovarian cancer in BRCA1 mutation carriers, compared with those with a BMI less than 20.8 kg/m2 (Q4 vs. Q1 HR, 2.13; 95% CI, 1.04-4.36; P = 0.04). There were no significant associations between height or BMI at age 18 and risk of ovarian cancer. CONCLUSIONS: Adult weight gain is a risk factor for ovarian cancer in women with a BRCA1 or BRCA2 mutation. IMPACT: These findings emphasize the importance of maintaining a healthy body weight throughout adulthood in women at high risk for ovarian cancer.

Survival from breast cancer in women with a BRCA2 mutation by treatment.

BACKGROUND: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation. METHODS: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features. RESULTS: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62-2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28-0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p = 0.56). CONCLUSIONS: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.

The impact of a cascade testing video on recipients' knowledge, cognitive message processing, and affective reactions: A formative evaluation.

Cascade genetic testing is essential to clarify cancer risk in families with hereditary breast and ovarian cancer syndrome (HBOC) due to pathogenic variants (PVs) in BRCA1 or BRCA2. To date, data suggest that family communication of genetic testing results, with or without the aid of clinical resources such as a provider-written family letter, is impacted by multiple barriers. These barriers eventually lead to sub-optimal uptake of cascade genetic testing. We designed a 2-min animated video that a proband can share with relatives to notify them that the proband has tested positive for a pathogenic variant in BRCA1 or BRCA2. We studied the video via hypothetical scenario in an unselected population to simulate the process by which a relative receives unsolicited genetics information about their family member. We assessed the impact of the video on three specific domains: knowledge, cognitive message processing, and affective reactions. A total of 399 participants recruited through Amazon Mechanical Turk completed the study, and 373 were analyzed. The video significantly improved content knowledge/recall (p < .0001) from pre- to post-video viewing, indicating effective message communication. Items used to measure cognitive processing showed preliminary tendencies toward systematic message processing, which could be desired in familial communication aimed at initiating a specific action-in this case, cascade genetic testing. A majority of participants (66%) reported positive affective reaction as they indicated that they would feel gratitude if they received the video message from a relative, and did not evidence a negative affective reaction to receiving the information. Our data suggest that a video message can effectively communicate information about cascade genetic testing to potential relatives with as little as two minutes of content. Our data suggest that video messaging to assist family communication is a reasonable approach that increases understanding and is unlikely to cause harm.