Pruthi, Sandhya

Objective: The purpose of this feasibility pilot study was to evaluate safety and adherence of a wearable brain sensing wellness device designed to reduce stress among healthcare professionals (HCP). Methods: A total of 40 HCP were invited to participate in an open-label pilot study. Participants were asked to use a brain sensing wearable device (MUSE-S™) on a daily basis to reduce their stress, for a total of 90 days. Total study participation duration was 180 days. Study enrollment began in August 2021 and ended December 2021. The exploratory outcomes included stress, depression, sleep, burn-out, resilience, quality of life, and cognition. Results: Among the 40 HCP in study, the majority were female (85%), white (87.5%) and with an average age of 41.3 ± 11.0 years (SD). Participants used the wearable device an average of 23.8 times over a 30-day period with a mean duration of 5.8 min with each use. Study results demonstrate the positive impact of guided mindfulness using the wearable device MUSE-S™ and its accompanying application (APP). A statistically significant improvement was found for a reduction in stress ( P < .001) and improvement in resilience ( P = .02), quality of life ( P = .003), and cognition ( P < .001). The majority (91.9%) of the participants indicated they felt more relaxed after using the device, and 73% indicated they would continue to use this device at end-of-study. No adverse effects were reported. Conclusion: Study results show that 3 to 10 min of guided meditation during work hours through the use of a brain sensing wearable device is safe and acceptable, with associated health benefits for HCP.

Abstract Background: Personalized breast cancer (BC) risk assessment depends on known traditional risk factors, specific germline mutations, and genome-wide polygenic risk scores (PRS). PRS explains a substantial proportion of genetic BC susceptibility. Accuracy of BC risk prediction may be improved by combining a PRS with traditional risk factors. We recently developed and validated a 149-SNP PRS for women of diverse ancestries using ancestry-informative genetic markers and combined this with version 7 of the Tyrer-Cuzick (TC) model to generate a Combined Risk Score (CRS). Here, we describe a pre-specified prospective longitudinal clinical validation of CRS as a predictor of BC risk. Methods: Women in the U.S. who were referred for clinical genetic testing between January 2017 and February 2019 were matched to medical and hospital claims in an anonymized dataset. Women with a pathogenic mutation in a BC-related gene were excluded from analysis. Follow-up began 4 months after testing and extended to the earliest date of BC diagnosis, censoring at the time of BC preventive treatment, or November 1, 2019. Incident BC events were determined by an ICD10 code of C50.* and confirmed by relevant treatment codes. CRS calibration was evaluated by the ratio of observed (O) to expected (E) incident BCs for the full cohort, and for women split into event-based 5-year CRS risk deciles. Cox proportional hazards models were used to evaluate discriminatory accuracy in terms of hazard ratios (HR) with 95% confidence intervals (CI) and p-values from likelihood ratio chi-squared statistics. Kaplan-Meier analysis was used to examine risk for women split into high- or low-risk groups according to a 3% 5-year CRS risk threshold. Results: 130,058 women with 148,349 total patient years met study eligibility criteria and were matched to claims data. Over a median (range) follow-up of 12.1 (4.0-29.5) months, 340 incident BC events were observed. The CRS was well calibrated in the overall cohort with an O/E ratio of 1.11 (95% CI=0.99-1.23) and within deciles of predicted risk (Table). Importantly, in the highest risk decile, the O/E was 0.91 (95% CI=0.63-1.27) with CRS, but 0.67 (95% CI=0.46-0.94) with TC alone, illustrating the superior calibration of CRS. In a Cox model adjusted for age at testing, PRS had an HR per standard deviation (SD) of 1.48 (95% CI=1.33-1.64, p=2.55×10-13); the HR/SD was 1.43 (95% CI=1.29-1.59, p=1.61×10-11) after adjusting for family history. In a bivariate analysis using both CRS and TC to predict time to BC, CRS added significantly to the model after accounting for TC (HR/SD=2.89, 95% CI=2.12-3.94, p=1.20×10-11), whereas TC did not add significant information after accounting for CRS. 15,986 (12.3%) women were above the CRS high-risk threshold, including 123 with events. A total of 10,248 (7.9%) women were reclassified by the CRS model compared to the TC model. Among women who were classified as high-risk by TC, 32.6% were reclassified as low-risk by CRS; among those classified as low-risk by TC, 4.3% were reclassified as high-risk by CRS. The CRS high-risk group experienced events at over three times the rate of the low-risk group (HR=3.75, 95% CI=3.00-4.68, p=6.39×10-27). Conclusion: The CRS was well-calibrated in predicting BC and significantly improved upon a traditional risk factor model. Clinical use of the CRS may lead to improved BC prevention and screening strategies. Table: Absolute risk calibration by 5-year risk decile Incidence is reported per 1,000 women-years. 34 breast cancers were observed per decile. Citation Format: Brent Mabey, Elisha Hughes, Braden Probst, Holly J. Pederson, Timothy Simmons, Brian Morris, Brooke Hullinger, Susan Domchek, Charis Eng, Monique Gary, Jennifer Klemp, Semanti Mukherjee, Vijai Joseph, Kenneth Offit, Olufunmilayo I. Olopade, Sandhya Pruthi, Allison W. Kurian, Mark E. Robson, Pat Whitworth, Susanne Wagner, Jerry Lanchbury, Thomas Slavin, Alexander Gutin. PD14-05 Prospective longitudinal validation of a breast cancer risk prediction model in a cohort of 130,058 women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-05.

Abstract Background: Despite evidence of substantial breast cancer risk reduction, few high-risk women adopt chemopreventive medications such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Women with benign breast disease, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have an increased risk of developing breast cancer and derive a greater benefit from antiestrogens compared to other high-risk women. Reasons for low uptake of chemoprevention include insufficient patient and clinician knowledge about antiestrogens, time constraints during the clinical encounter, and concerns about side effects. To address these barriers, we have developed patient and provider web-based decision support tools to improve informed choice about breast cancer chemoprevention among women with AH or LCIS. Study design: We are conducting a cluster-randomized controlled trial of clinical decision support to improve chemoprevention informed choice among women with AH or LCIS and their treating providers. Twenty-six U.S. sites through the SWOG Cancer Research Network were randomly assigned 1:1 to standard educational materials alone or in combination with the patient-centered decision aid (RealRisks) and provider decision support tool (BNAV). A total of 415 patients and 200 healthcare providers will be recruited from these sites. RealRisks consists of interactive modules to calculate personalized breast cancer risk and elicit preferences on chemoprevention. The modules are available in English and Spanish. BNAV is comprised of self-directed case-based learning modules on breast cancer risk assessment and chemoprevention. Patients complete questionnaires at baseline, 6 and 12 months. Providers complete surveys at baseline and after their enrolled patient’s 6-month clinical encounter. The primary endpoint is chemoprevention informed choice at 6 months, using a measure combining knowledge, attitude, and intention scales. Secondary endpoints include perceived breast cancer risk/worry, chemoprevention knowledge/intention, decision conflict/regret, shared decision-making, and chemoprevention uptake. For patients who begin chemoprevention, adherence and reasons for discontinuation are assessed annually for up to 5 years. Barriers and facilitators to implementing RealRisks and BNAV into clinic workflow will be assessed by conducting patient and provider interviews at baseline and mid-implementation. Eligibility criteria: Eligible patients include women, age 35-74 years, with AH or LCIS, no history of breast cancer, no prior use of SERMs or AIs, no bilateral mastectomies, English or Spanish-speaking, and access to the internet. Eligible providers include breast surgeons, medical oncologists, primary care providers, and physician extenders who see patients with AH or LCIS. Statistical methods: We have 90% power to detect a 15% increase in the frequency of chemoprevention informed choice with a 1-sided 0.025 level test, assuming an intraclass correlation (ICC) of 0.02 to account for clustering, roughly equal accrual at each site, 10% loss to follow-up, and ≤10% event rate in the control arm. Current/target accrual: The trial was activated on 9/1/2020. As of 7/7/2022, all 26 sites have been randomized, 157/200 providers and 184/415 patients have been enrolled. Discussion: Our hybrid effectiveness/implementation study seeks to evaluate the effectiveness of a multi-level intervention in promoting informed decision-making about breast cancer chemoprevention. Study results will provide valuable insights on how the decision support tools are integrated in diverse clinical settings. Citation Format: Katherine D. Crew, Garnet Anderson, Kathryn Arnold, Andrew Stieb, Jacquelyn N. Amenta, Cynthia Law, Ana Sandoval-Leon, Sarah Colonna, Tari King, Debra Mangino, Sandhya Pruthi, Maria Grosse Perdekamp, Christa Braun-Inglis, Stacy Krisher, Lisa Yee, Danielle Bertoni, Samantha Seaward, Kari B. Wisinski, Justin Floyd, Corrine Zarwan, Tarah J. Ballinger, Lindi VanderWalde, Masey M. Ross, Preston Steen, Shelly Lo, Alison Conlin, Kathleen Yost, John Ellerton, Erin Lin, Holly J. Pederson, Sagar Sardesai, Cheryl Jernigan, Dawn Hershman, Marian L. Neuhouser, Banu K. Arun, Rita Kukafka. SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-15-01.

Introduction Mayo Clinic Connect is an online community of over 100,000 members who support each other through sharing lived experience when facing and managing new diagnoses. The community is moderated by Mayo Clinic staff and volunteer patient mentors. Methods Mayo Clinic breast clinic patients undergoing evaluation received a binder of support resources including a brochure about Mayo Clinic Connect at visits between January and May of 2019. Surveys were distributed at subsequent visits between May and December of 2019 to assess patient awareness about the online resource, participation frequency, purpose of use, and benefits for members, as well as reasons for not joining (non-members). The primary aim was to assess patient resilience, coping, and self-management after joining the online community. Results Nine hundred surveys were distributed, and 102 participants completed surveys between May and December 2019. Forty-five percent ( n = 46) had heard about Mayo Clinic Connect; 34% ( n = 15) through a brochure. The remainder heard about the community from a Mayo Clinic provider (43%; n = 19) or other resources (22%, n = 10; no response n = 2). Twenty percent ( n = 20) of survey participants registered as Breast Cancer group members, and most of this subgroup (55%; n = 11) reported understanding diagnosis, treatment plans, and finding peer support as reasons for joining. Seventy-five percent of Mayo Clinic Connect participants ( n = 15) reported the community met or exceeded expectations. Conclusion This pilot study reveals the potential positive impact of introducing an online peer support group into clinical care plans for patients coping with a new and anxiety-provoking cancer diagnosis.

Objective: The primary aim of this study was to evaluate the feasibility of collecting risk factor information and accessing digitized mammographic data in a medically marginalized population. A secondary aim was to examine the association between vitamin D status and mammographic density. Methods: Breast-screening examinations were provided for age-appropriate patients, and a referral for no-cost screening mammography was offered. Study participants were asked to undergo 25-hydroxyvitamin D testing at mammography and 1-year follow-up. Results: Of 62 women approached, 35 (56%) consented to participate. Of 32 participants who had baseline mammography, the median mammographic density measured by VolparaDensity (Volpara Solutions Limited) was 5.7%. After 1 year, 9 women obtained follow-up mammograms, with a median density of 5.7%. Vitamin D status was measured for 31 participants at baseline and 13 participants in the following year. Insufficient vitamin D status (<30 ng/mL) was noted in 77% at each time point. Mammographic density was not significantly correlated with vitamin D status ( P = .06). Conclusions: On the basis of this small pilot study, vitamin D insufficiency is common in this study population. Owing to the small sample size, an association between vitamin D insufficiency and breast density was not clear. Additional unexpected findings included substantial barriers in initial access to care and longitudinal follow-up in this population. Further study of these issues is needed.

Abstract Background: Preventive endocrine therapy (ET) has been proven extensively to decrease breast cancer (BC) risk by 50-65%. Despite this significant reduction, a small proportion of high risk women take ET, due to attitudes toward medications, inaccurate risk perception and drug side-effects. The addition of a polygenic risk score (PRS), comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)), to the standard risk calculator estimates, can be used to improve BC risk estimation. We previously reported on the influence of the PRS-adjusted BC risk estimates on the intent to use ET (Abstract, SABCS, 2019). Here we report on the influence of PRS-adjusted BC risk estimates on ET adherence at 1 and 2 year follow –up. We also report on ET side effects over this same time period. Methods: Women older than age 35 were eligible if they were deemed at high risk for BC by either a 5 year Gail Model risk of ≥3% or 10 year Tyrer-Cuzick risk (IBIS) of ≥5%. We excluded women with a personal history of BC or hereditary BC syndromes. At baseline, participants were counseled on their BC risk using standard risk calculators: Gail and IBIS risk scores (5 yr, 10 yr, & lifetime) and ET options were discussed, including benefits and risks. Blood samples were obtained and genotyped for 77 SNPs, and an updated BC -PRS risk report was shared with study participants that reflected the IBIS and Gail risk predictions for 5 yr, 10 yr, & lifetime BC risk with and without the PRS. A baseline self-reported questionnaire assessed understanding of BC risk and decision to take ET. Follow-up questionnaires at 1 and 2 years assessed self-reported ET adherence and ET side effects (vasomotor symptoms, vaginal symptoms, sexual dysfunction, weight gain, GI symptoms, headaches, breast sensitivity, mood changes, and joint pain). Adherence to ET at 1 and 2 year follow-up was stratified by three categories of lifetime PRS-BC risk: 0-20%; 20-40%; 40-100%. Results: 151 women at Mayo Clinic Rochester and CancerCare Manitoba were enrolled in the study from 2016 to 2017. Of the 149 participants with evaluable data at 1 and 2 year follow-up, 57 (38%) started on ET therapy, all within 1 year of the baseline visit; 43 (29%) were taking ET at 1 year and 33 (22%) were taking ET at 2 year follow-up, representing a discontinuation rate of 26% at 1 year and 42% at 2 year follow-up. Adherence to ET use at 1 year and 2 year follow-ups correlated significantly with the category of PRS-BC risk estimation: at 1 year follow up, 17% of those in the lowest PRS-IBIS risk category, 23% in the middle risk category and 50% of those in the highest risk category were taking ET (p=0.001). At 2 year follow up, 12% of those in the lowest PRS-IBIS risk category, 18% in the middle risk category and 38% of those in the highest risk category were taking ET (p=0.008). At 1 year follow up, participants taking ET reported significantly more bothersome symptoms of vaginal itching (p=0.010), weight gain (p=0.015) and joint pain (p=0.044), compared with those not on ET. There was a trend towards increased irritability and mood swings on those taking ET (p=0.059). At year 2 there was no significant difference in side effects between those taking and not taking ET. Conclusion: Adherence to ET in a population of women at high risk for BC decreased overtime and strongly correlated with the level of risk, with 38% of those at highest risk of breast cancer taking ET at 2 year follow up. Side effects of vaginal itching, weight gain and body aches were more common on those taking ET versus not taking ET at the 1 year follow-up, but did not differ at 2 year follow-up, possibly due to the fact that those with the most bothersome symptoms have discontinued ET by the 2 year follow up. Citation Format: Daniela Stan, Julian Kim, Daniel Schaid, Erin Carlson, Andrew Cooke, Christina A. Kim, Benjamin Goldenberg, Jason Sinnwell, Debjani Grenier, Amy Degnim, Fergus Couch, Celine Vachon, Sandhya Pruthi. Influence of a breast cancer polygenic risk score on adherence to preventive endocrine therapy in high risk women at 1 and 2 year follow-up: The genetic risk estimate (GENRE) trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-02.

Abstract Purpose: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors—a population with breast cancer risk comparable with BRCA mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk. Patients and Methods: We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints. Results: Seventy-two participants (low-dose tamoxifen: n = 34, placebo: n = 38) enrolled at a median age of 43.8 years (35–49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (P = 0.02) and IGF1 levels (P &lt; 0.0001), and higher IGFBP-3 levels (P = 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3–4 adverse events related to low-dose tamoxifen. Conclusions: In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.