Applying theories, models, and frameworks to help genetic counselors and students achieve clinical and professional goals.

Some genetic counselors (GCs) may find theories, models, and frameworks (TMFs) useful in clinical skills selection and when reflecting on or evaluating genetic counseling practice. This paper aims to demonstrate how TMFs can be used to postulate how different skills may impact patients'/clients' decisions, behaviors, and outcomes and consider how multiple TMFs can inform the use of various skills or strategies to achieve different goals. Additionally, we provide examples of TMFs that may help GCs in nonclinical aspects of their work, such as implementing and evaluating new interventions or service delivery models. To guide the selection of appropriate TMFs, we provide a set of questions to consider and include examples of skills and approaches that align with different TMFs. While TMFs provide a structured approach and valuable guidance that may help advance genetic counseling practice, they have certain limitations. Additional research is necessary to determine the effectiveness of using TMFs to guide clinical practice and improve patient/client outcomes.

Facilitating return of actionable genetic research results from a biobank repository: Participant uptake and utilization of digital interventions.

Research participants report interest in receiving genetic research results. How best to return results remains unclear. In this randomized pilot study, we sought to assess the feasibility of returning actionable research results through a two-step process including a patient-centered digital intervention as compared with a genetic counselor (GC) in the Penn Medicine biobank. In Step 1, participants with an actionable result and procedural controls (no actionable result) were invited to digital pre-disclosure education and provided options for opting out of results. In Step 2, those with actionable results who had not opted out were randomized to receive results via a digital disclosure intervention or with a GC. Five participants (2%) opted out of results after Step 1. After both steps, 52 of 113 (46.0%) eligible cases received results, 5 (4.4%) actively declined results, 34 (30.1%) passively declined, and 22 (19.5%) could not be reached. Receiving results was associated with younger age (p < 0.001), completing pre-disclosure education (p < 0.001), and being in the GC arm (p = 0.06). Being older, female, and of Black race were associated with being unable to reach. Older age and Black race were associated with passively declining. Forty-seven percent of those who received results did not have personal or family history to suggest the mutation, and 55.1% completed clinical confirmation testing. The use of digital tools may be acceptable to participants and could reduce costs of returning results. Low uptake, disparities in uptake, and barriers to confirmation testing will be important to address to realize the benefit of returning actionable research results.

Test-takers' perspectives on consumer genetic testing for hereditary cancer risk.

Purpose: With few exceptions, research on consumer genetic testing for hereditary cancer risk has focused on tests with limited predictive value and clinical utility. Our study advances the existing literature by exploring the experiences and behaviors of individuals who have taken modern consumer genetic tests for cancer susceptibility that, unlike earlier tests, screen for medically significant variants. Methods: We interviewed 30 individuals who had undergone consumer genetic testing for hereditary cancer risk between 2014 and 2019. We explored participants' pre-test sentiments (7 items), experiences receiving results (5 items), behavioral and health-related changes (6 items), and attitudes and beliefs (3 items). Data were analyzed for thematic content. Results: Most participants reported a personal (n = 6) and/or family history (n = 24) of cancer, which influenced their choice to pursue testing. Before testing, most participants did not consult with a physician (n = 25) or receive genetic counseling (n = 23). Nevertheless, the majority felt that they understood test-related information (n = 20) and their results (n = 20), though a considerable number reported experiencing negative emotions related to their results. Most also shared their results with family members (n = 27). Overall, participants' attitudes towards consumer genetic testing for cancer risk were predominantly positive (n = 23). Conclusion: This study offers new insights into how individuals use and perceive modern consumer genetic tests for hereditary cancer risk, focusing on their perceptions of the risks, benefits, and limitations of these services. Understanding test-takers' perspectives can potentially inform improvements aimed at ensuring that tests meet users' needs and deliver clinically valuable genetic risk assessments.

Clinical management of TP53 mosaic variants found on germline genetic testing.

BACKGROUND: Germline heterozygous TP53 pathogenic variants (PVs) cause Li Fraumeni Syndrome (LFS, OMIM#151623). TP53 PVs at lower-than-expected variant allele frequencies (VAF) may reflect postzygotic mosaicism (PZM) or clonal hematopoiesis (CH); however, no guidelines exist for workup and clinical management. PATIENTS AND METHODS: Retrospective analysis of probands who presented to an academic cancer genetics program with a TP53 PV result on germline genetic testing. RESULTS: Twenty-one of 125 unrelated probands (17 %) were found to harbor a TP53 PV with VAF<30 % or a designation of "mosaic". A diagnosis of PZM was made in nine (43 %) due to a clinical phenotype consistent with LFS with (n = 8) or without (n = 1) positive ancillary tissue testing. Twelve patients (57 %) were diagnosed with presumed CH (pCH) due to a diagnosis of a myeloproliferative neoplasm, negative ancillary tissue testing, clinical phenotype not meeting LFS criteria, no cancer, and/or no first cancer age<50. Of the 19 patients with biological offspring, nine had either partial or complete offspring testing, all negative. CONCLUSIONS: Determining the etiology of low VAF TP53 PVs requires ancillary tissue testing and incorporation of clinical phenotype. Discerning PZM versus CH is important to provide optimal care and follow-up.

The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.

BACKGROUND: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. The ENGaging and Activating cancer survivors in Genetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing. METHODS: The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services. DISCUSSION: With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.

Childhood physical activity and pubertal timing: findings from the LEGACY girls study.

BACKGROUND: There is limited research on whether physical activity (PA) in early childhood is associated with the timing of pubertal events in girls. METHODS: We used data collected over 2011-16 from the LEGACY Girls Study (n = 984; primarily aged 6-13 years at study enrolment), a multicentre North American cohort enriched for girls with a breast cancer family history (BCFH), to evaluate if PA is associated with age at thelarche, pubarche and menarche. Maternal-reported questionnaire data measured puberty outcomes, PA in early childhood (ages 3-5 years) and total metabolic equivalents of organized PA in middle childhood (ages 7-9 years). We used interval-censored Weibull parametric survival regression models with age as the time scale and adjusted for sociodemographic factors, and we tested for effect modification by BCFH. We used inverse odds weighting to test for mediation by body mass index-for-age z-score (BMIZ) measured at study enrolment. RESULTS: Being highly active vs inactive in early childhood was associated with later thelarche in girls with a BCFH [adjusted hazard ratio (aHR) = 0.39, 95% CI = 0.26-0.59), but not in girls without a BCFH. In all girls, irrespective of BCFH, being in the highest vs lowest quartile of organized PA in middle childhood was associated with later menarche (aHR = 0.70, 95% CI = 0.50-0.97). These associations remained after accounting for potential mediation by BMIZ. CONCLUSION: This study provides new data that PA in early childhood may be associated with later thelarche in girls with a BCFH, also further supporting an overall association between PA in middle childhood and later menarche.

Association of Breast Cancer Odds with Background Parenchymal Enhancement Quantified Using a Fully Automated Method at MRI: The IMAGINE Study.

Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer. Materials and Methods This prospective case-control study included patients who underwent a bilateral breast MRI examination and were receiving care at one of three centers in the United States from November 2010 to July 2017. Breast volume, fibroglandular tissue (FGT) volume, and BPE were quantified using fully automated software. Fat volume was defined as breast volume minus FGT volume. BPE extent was defined as the proportion of FGT voxels with enhancement of 20% or more. Spearman rank correlation between quantitative BPE extent and Breast Imaging Reporting and Data System (BI-RADS) BPE categories assigned by an experienced board-certified breast radiologist was estimated. With use of multivariable logistic regression, breast cancer case-control status was regressed on tertiles (low, moderate, and high) of BPE, FGT volume, and fat volume, with adjustment for covariates. Results In total, 536 case participants with breast cancer (median age, 48 years [IQR, 43-55 years]) and 940 cancer-free controls (median age, 46 years [IQR, 38-55 years]) were included. BPE extent was positively associated with BI-RADS BPE (rs = 0.54; P < .001). Compared with low BPE extent (range, 2.9%-34.2%), high BPE extent (range, 50.7%-97.3%) was associated with increased odds of breast cancer (odds ratio [OR], 1.74 [95% CI: 1.23, 2.46]; P for trend = .002) in a multivariable model also including FGT volume (OR, 1.39 [95% CI: 0.97, 1.98]) and fat volume (OR, 1.46 [95% CI: 1.04, 2.06]). The association of high BPE extent with increased odds of breast cancer was similar for premenopausal and postmenopausal women (ORs, 1.75 and 1.83, respectively; interaction P = .73). Conclusion Objectively measured BPE at breast MRI is associated with increased breast cancer odds for both premenopausal and postmenopausal women. Clinical trial registration no. NCT02301767 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bokacheva in this issue.

Practical Guidance on Establishing a Molecular Testing Pathway for Alterations in Homologous Recombination Repair Genes in Clinical Practice for Patients with Metastatic Prostate Cancer.

CONTEXT: Prostate cancer is a molecularly heterogeneous disease that is amenable to diagnostic testing to identify patients potentially eligible for personalised treatments inform familial risk and provide relevant information about potential prognosis. Several guidelines support the integration of genomic testing in a shared decision-making framework so that both health care professionals (HCPs) and patients are involved in determining the best treatment approach. OBJECTIVE: To review current guidelines on molecular diagnostic testing for homologous recombination repair (HRR) gene alterations in patients with metastatic prostate cancer, with the aim of providing practical considerations for effective guideline implementation and establishment of an appropriate pathway for molecular diagnostic testing. EVIDENCE ACQUISITION: We undertook a nonsystematic narrative review of the literature using PubMed to identify current guidelines and recommendations on molecular diagnostic testing for BRCA and/or homologous recombination repair gene alterations (HRRm) in patients with prostate cancer. In addition, selected articles that included BRCA/HRRm testing in clinical trials in metastatic castration-resistant prostate cancer and real-world evidence were also evaluated. Websites for relevant societies were reviewed for molecular diagnostic guidelines not published on PubMed. EVIDENCE SYNTHESIS: Our review of guidelines published by several international societies that include molecular testing in prostate cancer identified variations in molecular testing approaches. The review of testing approaches used in clinical trials and real-world settings also highlighted several aspects that require improvement. Therefore, we compiled practical guidance for establishing an appropriate BRCA/HRR mutation testing pathway. CONCLUSIONS: While there are several challenges to molecular testing and interpretation of test results that require enhancement, a multidisciplinary team approach will empower HCPs and their institutions to improve on or initiate their own molecular testing pathways. This in turn will lead to improvements in management strategies for patients with metastatic prostate cancer, for whom better treatment outcomes is a significant unmet need. PATIENT SUMMARY: Establishing a molecular testing pathway in clinical practice for patients with metastatic castration-resistant prostate cancer will lead to fairer and more equal access to personalised treatments. This should lead to better outcomes, particularly for patients whose disease has spread to other areas of the body.

Uptake of Genetic Research Results and Patient-Reported Outcomes With Return of Results Incorporating Web-Based Predisclosure Education.

PURPOSE: We developed a web-based education intervention as an alternative to predisclosure education with a genetic counselor (GC) to reduce participant burden and provider costs with return of genetic research results. METHODS: Women at three sites who participated in 11 gene discovery research studies were contacted to consider receiving cancer genetic research results. Participants could complete predisclosure education through web education or with a GC. Outcomes included uptake of research results, factors associated with uptake, and patient-reported outcomes. RESULTS: Of 819 participants, 178 actively (21.7%) and 167 passively (20.4%) declined return of results; 474 (57.9%) were enrolled. Most (60.3%) received results although this was lower than the 70% uptake we hypothesized. Passive and active decliners were more likely to be Black, to have less education, and to have not received phone follow-up after the invitation letter. Most participants selected web education (88.5%) as an alternative to speaking with a GC, but some did not complete or receive results. Knowledge increased significantly from baseline to other time points with no significant differences between those who received web versus GC education. There were no significant increases in distress between web and GC education. CONCLUSION: Interest in web-based predisclosure education for return of genetic research results was high although it did not increase uptake of results. We found no negative patient-reported outcomes with web education, suggesting that it is a viable alternative delivery model for reducing burdens and costs of returning genetic research results. Attention to attrition and lower uptake of results among Black participants and those with less formal education are important areas for future research.

Health Data Sharing Perspectives of Patients Receiving Care in CancerLinQ-Participating Oncology Practices.

PURPOSE: CancerLinQ seeks to use data sharing technology to improve quality of care, improve health outcomes, and advance evidence-based research. Understanding the experiences and concerns of patients is vital to ensure its trustworthiness and success. METHODS: In a survey of 1,200 patients receiving care in four CancerLinQ-participating practices, we evaluated awareness and attitudes regarding participation in data sharing. RESULTS: Of 684 surveys received (response rate 57%), 678 confirmed cancer diagnosis and constituted the analytic sample; 54% were female, and 70% were 60 years and older; 84% were White. Half (52%) were aware of the existence of nationwide databases focused on patients with cancer before the survey. A minority (27%) indicated that their doctors or staff had informed them about such databases, 61% of whom indicated that doctors or staff had explained how to opt out of data sharing. Members of racial/ethnic minority groups were less likely to be comfortable with research (88% v 95%; P = .002) or quality improvement uses (91% v 95%; P = .03) of shared data. Most respondents desired to know how their health information was used (70%), especially those of minority race/ethnicity (78% v 67% of non-Hispanic White respondents; P = .01). Under half (45%) felt that electronic health information was sufficiently protected by current law, and most (74%) favored an official body for data governance and oversight with representation of patients (72%) and physicians (94%). Minority race/ethnicity was associated with increased concern about data sharing (odds ratio [OR], 2.92; P < .001). Women were less concerned about data sharing than men (OR, 0.61; P = .001), and higher trust in oncologist was negatively associated with concern (OR, 0.75; P = .03). CONCLUSION: Engaging patients and respecting their perspectives is essential as systems like CancerLinQ evolve.

Maternal and prenatal factors and age at thelarche in the LEGACY Girls Study cohort: implications for breast cancer risk.

BACKGROUND: Earlier onset of breast development (thelarche) is associated with increased breast cancer risk. Identifying modifiable factors associated with earlier thelarche may provide an opportunity for breast cancer risk reduction starting early in life, which could especially benefit girls with a greater absolute risk of breast cancer due to family history. METHODS: We assessed associations of maternal pre-pregnancy body mass index (BMI), physical activity during pregnancy, gestational weight gain and daughters' weight and length at birth with age at thelarche using longitudinal Weibull models in 1031 girls in the Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study-a prospective cohort of girls, half of whom have a breast cancer family history (BCFH). RESULTS: Girls whose mothers had a pre-pregnancy BMI of ≥25 and gained ≥30 lbs were 57% more likely to experience earlier thelarche than girls whose mothers had a pre-pregnancy BMI of <25 and gained <30 lbs [hazard ratio (HR) = 1.57, 95% CI: 1.16, 2.12]. This association was not mediated by childhood BMI and was similar in girls with and without a BCFH (BCFH: HR = 1.41, 95% CI: 0.87, 2.27; No BCFH: HR = 1.62, 95% CI: 1.10, 2.40). Daughters of women who reported no recreational physical activity during pregnancy were more likely to experience earlier thelarche compared with daughters of physically active women. Birthweight and birth length were not associated with thelarche. CONCLUSION: Earlier thelarche, a breast cancer risk factor, was associated with three potentially modifiable maternal risk factors-pre-pregnancy BMI, gestational weight gain and physical inactivity-in a cohort of girls enriched for BCFH.

User and Usability Testing of a Web-Based Genetics Education Tool for Parkinson Disease: Mixed Methods Study.

BACKGROUND: Genetic testing is essential to identify research participants for clinical trials enrolling people with Parkinson disease (PD) carrying a variant in the glucocerebrosidase (GBA) or leucine-rich repeat kinase 2 (LRRK2) genes. The limited availability of professionals trained in neurogenetics or genetic counseling is a major barrier to increased testing. Telehealth solutions to increase access to genetics education can help address issues around counselor availability and offer options to patients and family members. OBJECTIVE: As an alternative to pretest genetic counseling, we developed a web-based genetics education tool focused on GBA and LRRK2 testing for PD called the Interactive Multimedia Approach to Genetic Counseling to Inform and Educate in Parkinson's Disease (IMAGINE-PD) and conducted user testing and usability testing. The objective was to conduct user and usability testing to obtain stakeholder feedback to improve IMAGINE-PD. METHODS: Genetic counselors and PD and neurogenetics subject matter experts developed content for IMAGINE-PD specifically focused on GBA and LRRK2 genetic testing. Structured interviews were conducted with 11 movement disorder specialists and 13 patients with PD to evaluate the content of IMAGINE-PD in user testing and with 12 patients with PD to evaluate the usability of a high-fidelity prototype according to the US Department of Health and Human Services Research-Based Web Design & Usability Guidelines. Qualitative data analysis informed changes to create a final version of IMAGINE-PD. RESULTS: Qualitative data were reviewed by 3 evaluators. Themes were identified from feedback data of movement disorder specialists and patients with PD in user testing in 3 areas: content such as the topics covered, function such as website navigation, and appearance such as pictures and colors. Similarly, qualitative analysis of usability testing feedback identified additional themes in these 3 areas. Key points of feedback were determined by consensus among reviewers considering the importance of the comment and the frequency of similar comments. Refinements were made to IMAGINE-PD based on consensus recommendations by evaluators within each theme at both user testing and usability testing phases to create a final version of IMAGINE-PD. CONCLUSIONS: User testing for content review and usability testing have informed refinements to IMAGINE-PD to develop this focused, genetics education tool for GBA and LRRK2 testing. Comparison of this stakeholder-informed intervention to standard telegenetic counseling approaches is ongoing.

Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer.

Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective. Twenty-five subjects enrolled. The combination of ruxolitinib and exemestane was safe, though anemia requiring transfusion in 5/15 (33%) at the 25 mg dose in stage 1 led to a reduction to 15 mg twice daily in stage 2 (with no additional transfusions). Clinical benefit rate (CBR) in the overall study population was 24% (95% CI 9.4-45.1); 6/25 patients demonstrated stable disease for ≥6 months. Median progression-free survival was 2.8 months (95% CI 2.6-3.9). Exploratory biomarkers revealed high levels of systemic inflammation and 60% harbored a high-risk IL-6 genotype. Pharmacodynamics demonstrated modest on-target inhibition of phosphorylated-STAT3 by ruxolitinib at a tolerable dose. Thus, ruxolitinib combined with exemestane at a tolerable dose was safe but minimally active in AI-resistant tumors of patients with high levels of systemic inflammation. These findings highlight the need for more potent and specific therapies targeting inflammation in MBC.

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.

Mother and Daughter Perspectives on Genetic Counseling and Testing of Adolescents for Hereditary Breast Cancer Risk.

OBJECTIVE: To evaluate the risks, benefits, and utility of testing for adult-onset hereditary breast and ovarian cancer (HBOC) in adolescents and young adults. STUDY DESIGN: We evaluated interest in genetic testing of adolescents for adult-onset HBOC genes through semistructured interviews with mothers and adolescents who had previously participated in breast cancer research or had pursued (mothers) clinical testing for HBOC. RESULTS: The majority of mothers (73%) and daughters (75%) were interested in the daughter having genetic testing and were motivated by the future medical utility and current social utility of relieving anxiety and allowing them to prepare. Mothers and daughters both reported that approximately 3 years in the future was the best time to test the daughter regardless of the current age of the daughter. Overall, both mothers and daughters expressed the importance of the involvement of the mother to provide educational and emotional support but ultimately it was the daughter's decision to test. Balancing the independence and maturity of the daughter while reinforcing communication and support within the dyad was a prominent theme throughout the interviews. CONCLUSIONS: There is interest among some high-risk adolescents and young adults to engage in genetic counseling and undergo testing. Providing pretest and posttest genetic counseling, assessing preferences for parent involvement, and offering psychosocial support may be important if genetic testing for HBOC is offered to adolescents and young adults before age 25 years.

Body mass index rebound and pubertal timing in girls with and without a family history of breast cancer: the LEGACY girls study.

BACKGROUND: Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty. METHODS: In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models. RESULTS: The median age at BMI rebound was 5.3 years (interquartile range: 3.6-6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83-0.97) and menarche (HR = 0.86; 95% CI = 0.79-0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development. CONCLUSIONS: Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk.

Patient Experiences, Trust, and Preferences for Health Data Sharing.

PURPOSE: Scholars have examined patients' attitudes toward secondary use of routinely collected clinical data for research and quality improvement. Evidence suggests that trust in health care organizations and physicians is critical. Less is known about experiences that shape trust and how they influence data sharing preferences. MATERIALS AND METHODS: To explore learning health care system (LHS) ethics, democratic deliberations were hosted from June 2017 to May 2018. A total of 217 patients with cancer participated in facilitated group discussion. Transcripts were coded independently. Finalized codes were organized into themes using interpretive description and thematic analysis. Two previous analyses reported on patient preferences for consent and data use; this final analysis focuses on the influence of personal lived experiences of the health care system, including interactions with providers and insurers, on trust and preferences for data sharing. RESULTS: Qualitative analysis identified four domains of patients' lived experiences raised in the context of the policy discussions: (1) the quality of care received, (2) the impact of health care costs, (3) the transparency and communication displayed by a provider or an insurer to the patient, and (4) the extent to which care coordination was hindered or facilitated by the interchange between a provider and an insurer. Patients discussed their trust in health care decision makers and their opinions about LHS data sharing. CONCLUSION: Additional resources, infrastructure, regulations, and practice innovations are needed to improve patients' experiences with and trust in the health care system. Those who seek to build LHSs may also need to consider improvement in other aspects of care delivery.

A randomized study of genetic education versus usual care in tumor profiling for advanced cancer in the ECOG-ACRIN Cancer Research Group (EAQ152).

BACKGROUND: Enthusiasm for precision oncology may obscure the psychosocial and ethical considerations associated with the implementation of tumor genetic sequencing. METHODS: Patients with advanced cancer undergoing tumor-only genetic sequencing in the National Cancer Institute Molecular Analysis for Therapy Choice (MATCH) trial were randomized to a web-based genetic education intervention or usual care. The primary outcomes were knowledge, anxiety, depression, and cancer-specific distress collected at baseline (T0), posteducation (T1) and after results (T2). Two-sided, 2-sample t tests and univariate and multivariable generalized linear models were used. RESULTS: Five hundred ninety-four patients (80% from NCI Community Oncology Research Program sites) were randomized to the web intervention (n = 293) or usual care (n = 301) before the receipt of results. Patients in the intervention arm had greater increases in knowledge (P for T1-T0 < .0001; P for T2-T0 = .003), but there were no significant differences in distress outcomes. In unadjusted moderator analyses, there was a decrease in cancer-specific distress among women (T0-T1) in the intervention arm but not among men. Patients with lower health literacy in the intervention arm had greater increases in cancer-specific distress and less decline in general anxiety (T0-T1) and greater increases in depression (T0-T2) in comparison with those receiving usual care. CONCLUSIONS: Web-based genetic education before tumor-only sequencing results increases patient understanding and reduces distress in women. Refinements to the intervention could benefit low-literacy groups and men.