A Randomized Trial of Two Remote Health Care Delivery Models on the Uptake of Genetic Testing and Impact on Patient-Reported Psychological Outcomes in Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, and Testing (GENERATE) Study.

BACKGROUND & AIMS: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes. METHODS: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3 months postintervention. RESULTS: A total of 424 families were randomized, including 601 participants (n = 296 Arm 1; n = 305 Arm 2), 90% of whom completed genetic testing (Arm 1 [87%]; Arm 2 [93%], P = .014). Arm 1 participants were significantly less likely to complete genetic testing compared with Arm 2 participants (adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). Among participants who completed patient-reported psychological outcomes questionnaires (Arm 1 [n = 194]; Arm 2 [n = 206]), the intervention did not affect mean anxiety, depression, or cancer worry scores. CONCLUSIONS: Remote genetic education and testing can be a successful and complementary option for delivering genetics care. (Clinicaltrials.gov, number NCT03762590).

Communication About Negative and Uncertain Results: Interactional Dilemmas During a Genetic Telehealth Consult.

This case study focuses on a video telehealth consult to discuss genetic testing results. Participants include a Genetic Counselor (GC) and a Patient (P) previously diagnosed with ovarian cancer who is currently undergoing chemotherapy treatments. Utilizing conversation analysis (CA), attention is first given to a series of interactional dilemmas as GC delivers and P responds to negative, uncertain, and complex test results. Specific findings address practices employed by GC to structure the encounter and establish authority, impacts on P's participation and understandings, recurring and at times problematic orientations to "negative" findings, and inherent ambiguities faced by GC and P when attempting to discern good and bad news. Close examination of these moments provides a unique opportunity to identify, describe, and explain genetic counseling as a co-produced, interactional achievement. These findings are then integrated with patient's post-counseling survey (susceptibility, anxiety, uncertainty, fear, and hope), including reported experiences which broaden understandings of the interactional environment. Specific recommendations are raised for improving counseling skills, enhancing patients' understandings, and building therapeutic alliances addressing both patients' emotional circumstances and the complexities of genetic test results.

Co-Localization of Gastrointestinal Stromal Tumors (GIST) and Peritoneal Mesothelioma: A Case Series.

PURPOSE: Gastrointestinal stromal tumor (GIST) is associated with increased risk of additional cancers. In this study, synchronous GIST, and peritoneal mesothelioma (PM) were characterized to evaluate the relationship between these two cancers. METHODS: A retrospective chart review was conducted for patients diagnosed with both GIST and PM between July 2010 and June 2021. Patient demographics, past tumor history, intraoperative reports, cross-sectional imaging, peritoneal cancer index (PCI) scoring, somatic next-generation sequencing (NGS) analysis, and histology were reviewed. RESULTS: Of 137 patients who underwent primary GIST resection from July 2010 to June 2021, 8 (5.8%) were found to have synchronous PM, and 4 patients (50%) had additional cancers and/or benign tumors. Five (62.5%) were male, and the median age at GIST diagnosis was 57 years (range: 45-76). Seventy-five percent of GISTs originated from the stomach. Of the eight patients, one patient had synchronous malignant mesothelioma (MM), and the remaining had well-differentiated papillary mesothelioma (WDPM), which were primarily located in the region of the primary GIST (89%). The median PCI score was 2 in the WDPM patients. NGS of GIST revealed oncogenic KIT exon 11 (62.5%), PDGFRA D842V (25%), or SDH (12.5%) mutations, while NGS of the MM revealed BAP1 and PBRM1 alterations. CONCLUSIONS: One in 17 GIST patients undergoing resection in this series have PM, which is significantly higher than expected if these two diseases were considered as independent events. Our results indicate that synchronous co-occurrence of GIST and PM is an underrecognized finding, suggesting a possible relationship that deserves further investigation.

Risk estimation, anxiety, and breast cancer worry in women at risk for breast cancer: A single-arm trial of personalized risk communication.

OBJECTIVE: Elevated anxiety and breast cancer worry can impede mammographic screening and early breast cancer detection. Genetic advances and risk models make personalized breast cancer risk assessment and communication feasible, but it is unknown whether such communication of risk affects anxiety and disease-specific worry. We studied the effect of a personalized breast cancer screening intervention on risk perception, anxiety, and breast cancer worry. METHODS: Women with a normal mammogram but elevated risk for breast cancer (N = 122) enrolled in the Athena Breast Health risk communication program were surveyed before and after receiving a letter conveying their breast cancer risk and a breast health genetic counselor consultation. We compared breast cancer risk estimation, anxiety, and breast cancer worry before and after risk communication and evaluated the relationship of anxiety and breast cancer worry to risk estimation accuracy. RESULTS: Women substantially overestimated their lifetime breast cancer risk, and risk communication somewhat mitigated this overestimation (49% pre-intervention, 42% post-intervention, 13% Gail model risk estimate, P < .001). Both general anxiety and breast cancer worry declined significantly after risk communication in women with high baseline anxiety. Baseline anxiety and breast cancer worry were essentially unrelated to risk estimation accuracy, but risk communication increased alignment of worry with accuracy of risk assessment. CONCLUSIONS: Personalized communication about breast cancer risk was associated with modestly improved risk estimation accuracy in women with relatively low anxiety and less anxiety and breast cancer worry in women with higher anxiety. We detected no negative consequences of informing women about elevated breast cancer risk.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.

A Rapid Systematic Review of Outcomes Studies in Genetic Counseling.

As healthcare reimbursement is increasingly tied to value-of-service, it is critical for the genetic counselor (GC) profession to demonstrate the value added by GCs through outcomes research. We conducted a rapid systematic literature review to identify outcomes of genetic counseling. Web of Science (including PubMed) and CINAHL databases were systematically searched to identify articles meeting the following criteria: 1) measures were assessed before and after genetic counseling (pre-post design) or comparisons were made between a GC group vs. a non-GC group (comparative cohort design); 2) genetic counseling outcomes could be assessed independently of genetic testing outcomes, and 3) genetic counseling was conducted by masters-level genetic counselors, or non-physician providers. Twenty-three papers met the inclusion criteria. The majority of studies were in the cancer genetic setting and the most commonly measured outcomes included knowledge, anxiety or distress, satisfaction, perceived risk, genetic testing (intentions or receipt), health behaviors, and decisional conflict. Results suggest that genetic counseling can lead to increased knowledge, perceived personal control, positive health behaviors, and improved risk perception accuracy as well as decreases in anxiety, cancer-related worry, and decisional conflict. However, further studies are needed to evaluate a wider array of outcomes in more diverse genetic counseling settings.

FGFR1 and NTRK3 actionable alterations in "Wild-Type" gastrointestinal stromal tumors.

BACKGROUND: About 10-15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies. METHODS: We performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations. RESULTS: We identified 24 GIST lacking alterations in the canonical KIT/PDGFRA/RAS pathways, including 12 without SDHx alterations. These 24 patients were mostly adults (96%). The tumors had a 46% rate of nodal metastases. These 24 GIST were more commonly mutated at 7 genes: ARID1B, ATR, FGFR1, LTK, SUFU, PARK2 and ZNF217. Two tumors harbored FGFR1 gene fusions (FGFR1-HOOK3, FGFR1-TACC1) and one harbored an ETV6-NTRK3 fusion that responded to TRK inhibition. In an independent sample set, we identified 5 GIST cases lacking alterations in the KIT/PDGFRA/SDHx/RAS pathways, including two additional cases with FGFR1-TACC1 and ETV6-NTRK3 fusions. CONCLUSIONS: Using patient demographics, tumor characteristics, and CGP, we show that GIST lacking alterations in canonical genes occur in younger patients, frequently metastasize to lymph nodes, and most contain deleterious genomic alterations, including gene fusions involving FGFR1 and NTRK3. If confirmed in larger series, routine testing for these translocations may be indicated for this subset of GIST. Moreover, these findings can be used to guide personalized treatments for patients with GIST. Trial registration NCT 02576431. Registered October 12, 2015.

Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer.

Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study.

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry. METHODS: Patients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population. RESULTS: There were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis. CONCLUSIONS: This is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies.

Genetic/familial high-risk assessment: breast and ovarian, version 1.2014.

During the past few years, several genetic aberrations that may contribute to increased risks for development of breast and/or ovarian cancers have been identified. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian focus specifically on the assessment of genetic mutations in BRCA1/BRCA2, TP53, and PTEN, and recommend approaches to genetic testing/counseling and management strategies in individuals with these mutations. This portion of the NCCN Guidelines includes recommendations regarding diagnostic criteria and management of patients with Cowden Syndrome/PTEN hamartoma tumor syndrome.

The psychosocial impact of lymphedema-related distress among breast cancer survivors in the WHEL Study.

OBJECTIVE: Lymphedema is a distressing and chronic condition affecting up to 30% of breast cancer survivors. Using a cross-sectional study design, we examined the impact of self-reported lymphedema-related distress on psychosocial functioning among breast cancer survivors in the Women's Healthy Eating and Living Study. The Women's Healthy Eating and Living Study has a dataset that includes self-report data on lymphedema status, symptoms, and distress. METHODS: Chi-square tests and binary logistic regression models were used to examine how specific participant characteristics, including lymphedema-related distress, were associated with physical health and mental health as measured by the SF-36-Item Health Survey and depressive symptoms assessed by the Center for Epidemiologic Studies Depression Scale screening form. RESULTS: Of the 2431 participants included in the current study population, 692 (28.5%) self-reported ever having lymphedema. A total of 335 (48.9%) women reported moderate to extreme distress as a result of their lymphedema and were classified as having lymphedema-related distress. The logistic regression models showed that women with lymphedema-related distress had 50% higher odds of reporting poor physical health (p = 0.01) and 73% higher odds of having poor mental health (p < 0.01) when compared with women without lymphedema. In contrast, even though lymphedema-related distress was significantly associated (p = 0.03) with elevated depressive symptoms in the bivariate analyses, it was not significant in the logistic regression models. CONCLUSION: Breast cancer survivors with lymphedema-related distress had worse physical health and mental health outcomes than women with lymphedema who were not distressed and women with no lymphedema. Our findings provide further evidence of the relationship between lymphedema and psychosocial outcomes in breast cancer survivors.

Patient compliance with a health care provider referral for an occupational therapy lymphedema consult.

PURPOSE: Limited information exists on breast cancer patients' compliance to attend outpatient appointments with an occupational therapy (OT) lymphedema specialist. The objectives of this study were (1) to examine patient compliance with a health care provider referral for an OT lymphedema consult and (2) to identify potential barriers to compliance. METHODS: A retrospective chart review of female breast cancer patients at the UC San Diego Health System was conducted. Electronic medical records were queried for breast cancer patients, who received a health care provider referral for an OT lymphedema consult between June 1, 2010 and December 31, 2011. Descriptive statistics and Fisher's exact chi-square tests were used to examine how specific participant characteristics were associated with attending an OT appointment. RESULTS: A total of 210 female patients received an OT referral from a health care provider related to their breast cancer diagnosis. Forty-three (20.5%) patients did not attend an OT appointment. Non-attenders were more likely to have had fewer lymph nodes removed (P<0.01) when compared to attenders. The two most common barriers to attendance were the presence of health problems and undergoing chemotherapy and/or radiation at the time of the OT referral. CONCLUSIONS: While most breast cancer patients attended recommended OT lymphedema consults, a substantial number of women might benefit from further education about OT for lymphedema prevention following breast cancer treatment. Further research to understand barriers to attendance is recommended, particularly among women with only sentinel nodes removed.

Characteristics of genomic test consumers who spontaneously share results with their health care provider.

The purpose of this study was to evaluate the characteristics of direct-to-consumer (DTC) genomic test consumers who spontaneously shared their test results with their health care provider. Utilizing data from the Scripps Genomic Health Initiative, we compared demographic, behavioral, and attitudinal characteristics of DTC genomic test consumers who shared their results with their physician or health care provider versus those who did not share. We also compared genomic risk estimates between the two groups. Of 2,024 individuals assessed at approximately 6 months post testing, 540 individuals (26.5%) reported sharing their results with their physician or health care provider. Those who shared were older (p < .001), had a higher income (p = .01), were more likely to be married (p = .005), and were more likely to identify with a religion (p = .004). As assessed prior to undergoing testing, sharers also reported higher levels of exercise (p = .003), lower fat intake (p = .02), fewer overall concerns about testing (p = .001), and fewer concerns related to the privacy of their genomic information (p = .03). The genomic disease risk estimates disclosed were not associated with sharing. Thus, in a DTC genomic testing context, physicians and other health care providers may be more likely to encounter patients who are more health conscious and have fewer concerns about the privacy of their genomic information. Genomic risk itself does not appear to be a primary determinant of sharing behavior among consumers.

Germline DNA damage response gene mutations as predictive biomarkers of immune checkpoint inhibitor efficacy.

Background: Impaired DNA damage response (DDR) can affect immune checkpoint inhibitors (ICI) efficacy and lead to heightened immune activation. We assessed the impact of pathogenic or likely pathogenic (P/LP) germline DDR mutations on ICI response and toxicity. Materials and methods: A retrospective analysis of 131 cancer patients with germline DNA testing and ICI treatment was performed. Results: Ninety-two patients were DDR-negative (DDR-), and 39 had ≥1 DDR mutation (DDR+). DDR+ patients showed higher objective response rates (ORRs) compared to DDR- in univariate and multivariable analyses, adjusting for age and metastatic disease (62% vs. 23%, unadjusted OR = 5.41; 95% CI, 2.41-12.14; adjusted OR 5.94; 95% CI, 2.35-15.06). Similar results were seen in mismatch repair (MMR), DDR pathways with intact MMR (DDR+MMRi), and homologous recombination (HR) subgroups versus DDR- (adjusted OR MMR = 24.52; 95% CI 2.72-221.38, DDR+MMRi = 4.26; 95% CI, 1.57-11.59, HR = 4.74; 95% CI, 1.49-15.11). DDR+ patients also had higher ORRs with concurrent chemotherapy (82% vs. 39% DDR-, p=0.03) or concurrent tyrosine kinase inhibitors (50% vs. 5% DDR-, p=0.03). No significant differences in immune-related adverse events were observed between DDR+ and DDR- cohorts. Conclusion: P/LP germline DDR mutations may enhance ICI response without significant additional toxicity.

Germline genetic testing for prostate cancer: Ordering trends in the era of expanded hereditary cancer screening recommendations.

PURPOSE: The availability of targeted therapies for advanced prostate cancer led to the expansion of national guidelines recommending germline genetic testing. The aim of this study was to describe recent trends in germline test ordering patterns for patients with prostate cancer. MATERIALS AND METHODS: A retrospective cohort analysis of patients with prostate cancer who underwent germline testing through a single commercial laboratory (Invitae Corporation) between 2015-2020 was performed. Ordering trends between provider medical specialties were compared. Our primary hypothesis was that the proportion of tests ordered by urologists would increase over time. RESULTS: In total, 17,256 prostate cancer patients underwent germline genetic testing; 14,400 patients had an ordering provider with an associated medical specialty and were included in the final comparison cohort. Total prostate cancer patients undergoing germline testing increased quarterly from 21 in Q2 of 2015 to 1,509 in Q3 of 2020. The proportion of tests ordered by urologists increased from 0% in Q2 2015 to 8.3% in Q3 2020 (P < 0.001). Compared to medical genetics, medical oncology, and other specialties, urology ordered more tests for patients under 70 years old (66% vs 51%-55%, P <0.004) and for patients who reported negative family history (25% vs 12%-20%, P = 0.012). CONCLUSIONS: As awareness and indications for germline testing continue to expand, aggregate ordering volume is increasing, and urologists are becoming more involved in facilitating testing. This highlights the continued importance of educating urologists on the indications for and implications of germline genetic testing, as well as providing tools to support implementation.

Receiving a pathogenic variant in a population breast cancer screening trial: a mixed method study.

INTRODUCTION: Risk-based breast cancer screening aims to address persistent high morbidity and mortality. This study examines the experience of participants in the WISDOM (Women Informed to Screen Depending on Measures of Risk) trial who received a pathogenic variant in one of nine high or moderate penetrance breast cancer genes. METHODS: Participants completed a brief survey (n=181) immediately following results disclosure and one year later. Descriptive statistics were computed and comparisons between participants at different risk levels were performed using Fisher's Exact and McNemar's tests. Analysis of qualitative interviews (n=42) at 2-4 weeks and six months post results disclosure compared responses at the two timepoints, and explained and elaborated on the survey data. RESULTS: 66.3% of survey respondents felt very or moderately prepared to receive genomic results. At the T1 survey 80.7% of participants had shared the genetic result with a blood relative, increasing to 88.4% at T2; providing information and encouraging cascade testing were the most common reasons for sharing. Communication with a blood relative, other health care providers beyond the primary care provider, and cascade testing were higher for participants with a high risk than low or moderate risk genomic finding. Qualitative interviews elucidated varied reasons why participants felt (un)prepared for the results, including whether or not they had a family history of breast cancer, and illustrate the complexity of decision-making about sharing results. CONCLUSIONS: Although most participants communicated results with family members and health care providers in accord with their risk level, questions remain about how to adequately prepare individuals to receive pathogenic results, ensure timely and accessible follow-up care, and facilitate genetic counseling and cascade testing of at-risk relatives in the setting of population risk-based screening.

Evaluation of ultra-deep targeted sequencing for personalized breast cancer care.

INTRODUCTION: The increasing number of targeted therapies, together with a deeper understanding of cancer genetics and drug response, have prompted major healthcare centers to implement personalized treatment approaches relying on high-throughput tumor DNA sequencing. However, the optimal way to implement this transformative methodology is not yet clear. Current assays may miss important clinical information such as the mutation allelic fraction, the presence of sub-clones or chromosomal rearrangements, or the distinction between inherited variants and somatic mutations. Here, we present the evaluation of ultra-deep targeted sequencing (UDT-Seq) to generate and interpret the molecular profile of 38 breast cancer patients from two academic medical centers. METHODS: We sequenced 47 genes in matched germline and tumor DNA samples from 38 breast cancer patients. The selected genes, or the pathways they belong to, can be targeted by drugs or are important in familial cancer risk or drug metabolism. RESULTS: Relying on the added value of sequencing matched tumor and germline DNA and using a dedicated analysis, UDT-Seq has a high sensitivity to identify mutations in tumors with low malignant cell content. Applying UDT-Seq to matched tumor and germline specimens from the 38 patients resulted in a proposal for at least one targeted therapy for 22 patients, the identification of tumor sub-clones in 3 patients, the suggestion of potential adverse drug effects in 3 patients and a recommendation for genetic counseling for 2 patients. CONCLUSION: Overall our study highlights the additional benefits of a sequencing strategy, which includes germline DNA and is optimized for heterogeneous tumor tissues.

Early Ascertainment of Breast Cancer Diagnoses Comparing Self-Reported Questionnaires and Electronic Health Record Data Warehouse: The WISDOM Study.

PURPOSE: The goal of this study was to use real-world data sources that may be faster and more complete than self-reported data alone, and timelier than cancer registries, to ascertain breast cancer cases in the ongoing screening trial, the WISDOM Study. METHODS: We developed a data warehouse procedural process (DWPP) to identify breast cancer cases from a subgroup of WISDOM participants (n = 11,314) who received breast-related care from a University of California Health Center in the period 2012-2021 by searching electronic health records (EHRs) in the University of California Data Warehouse (UCDW). Incident breast cancer diagnoses identified by the DWPP were compared with those identified by self-report via annual follow-up online questionnaires. RESULTS: Our study identified 172 participants with confirmed breast cancer diagnoses in the period 2016-2021 by the following sources: 129 (75%) by both self-report and DWPP, 23 (13%) by DWPP alone, and 20 (12%) by self-report only. Among those with International Classification of Diseases 10th revision cancer diagnostic codes, no diagnosis was confirmed in 18% of participants. CONCLUSION: For diagnoses that occurred ≥20 months before the January 1, 2022, UCDW data pull, WISDOM self-reported data via annual questionnaire achieved high accuracy (96%), as confirmed by the cancer registry. More rapid cancer ascertainment can be achieved by combining self-reported data with EHR data from a health system data warehouse registry, particularly to address self-reported questionnaire issues such as timing delays (ie, time lag between participant diagnoses and the submission of their self-reported questionnaire typically ranges from a month to a year) and lack of response. Although cancer registry reporting often is not as timely, it does not require verification as does the DWPP or self-report from annual questionnaires.