Ghosh, Karthik

Background/Objectives: Multi-cancer detection (MCD) tests have emerged as a promising tool to redefine the landscape of early cancer detection. Implementation of this novel technology will likely fall to primary care clinicians (PCC). The purpose of this study is to characterize and explore differences in PCCs perceptions and preferences towards MCD testing. Methods: Between March and May of 2023, this cross-sectional survey was administered to 281 PCCs, including physicians and advanced care providers practicing within an integrated healthcare system spanning five states. The survey collected data on self-reported characteristics, perceptions of MCD testing, and preferences for learning about MCD testing. Analysis was limited to those with no prior experience with MCD testing (N = 181, response rate 22.8%). Descriptive statistics summarized key variables and chi-square tests assessed differences in perceptions and preferences by key characteristics. Results: Most PCCs were interested in MCD testing (66.3%), but limited knowledge/awareness of MCD testing and confidence to manage patients with a positive test were observed, along with concerns around cost (76.7%) and misuse/poor implementation. The primary preferences for learning about MCD testing were online courses or classroom instruction (64.5%). Significant differences in perceptions and preferences for learning were observed by location, degree, and years in practice. Conclusions: PCCs in our study held positive views towards MCD testing, but gaps and variation in knowledge and confidence towards MCD testing and concerns around the cost and misuse/poor implementation were observed. While efforts to train and educate all PCCs on MCD testing is a critical first step, more research is needed to understand how best to support implementation tailored to individual and system-level needs and characteristics.

Background: Artificial intelligence (AI) platforms can potentially enhance clinical decision-making (CDM) in primary care settings. OpenEvidence (OE), an AI tool, draws from trusted sources to generate evidence-based medicine (EBM) recommendations to address clinical questions. However, its effectiveness in real-world primary care cases remains unknown. Objective: To evaluate the performance of OE in providing EBM recommendations for five common chronic conditions in primary care: hypertension, hyperlipidemia, diabetes mellitus type 2, depression, and obesity. Methods: Five patient cases were retrospectively analyzed. Physicians posed specific clinical questions, and OE responses were evaluated on clarity, relevance, evidence support, impact on CDM, and overall satisfaction. Four independent physicians provided ratings using a 0 to 4 scale. Results: OE provided accurate, evidence-based recommendations in all cases, aligning with physician plans. OE was scored on a scale of zero to four, where zero was very unclear, and four was very clear. Mean scores across cases were clarity (3.55 ± 0.60), relevance (3.75 ± 0.44), support (3.35 ± 0.49), and satisfaction (3.60 ± 0.60). However, the impact on CDM was limited (1.95 ± 1.05), as OE primarily reinforced rather than modified plans. Conclusion: OE was rated high in clarity, relevance, and evidence-based support, reinforcing physician decisions in common chronic conditions. While the impact on CDM was minimal due to the study’s retrospective nature, OE shows promise in augmenting the primary care physician. Prospective trials are needed to evaluate its utility in complex cases and multidisciplinary settings.

Abstract Background Benign breast disease (BBD) increases breast cancer (BC) risk progressively for women diagnosed with nonproliferative change, proliferative disease without atypia (PDWA), and atypical hyperplasia (AH). Leveraging data from 18 704 women in the Mayo BBD Cohort (1967-2013), we evaluated temporal trends in BBD diagnoses and how they have influenced associated BC risk over 4 decades. Methods BC risk trends associated with BBD were evaluated using standardized incidence ratios (SIRs) and age–period–cohort modeling across 4 eras—premammogram (1967-1981), precore needle biopsy (CNB) (1982-1992), transition to CNB (1993-2001), and CNB era (2002-2013). Results With a median follow-up of 15.8 years, 9.9% of women were diagnosed with BC (invasive and/or DCIS). From the premammogram era to the CNB era, we observed a significant increase in BC risk, rising from an SIR of 1.61 to 1.99. The proportion of proliferative BBD diagnoses (PDWA or AH) increased markedly over time (28.1%-49.7%), as did the proportion of DCIS events (11%-28%; χ2 P < .001). Within specific BBD categories, the risk of invasive BC increased modestly. Conclusions Absolute risk of BC within BBD categories remained stable, but the relative risk of BC after BBD increased over time due to notable increases in higher risk BBD lesions, specifically PDWA and AH. These findings illustrate how evolving screening practices have changed the risk profile of BBD and should inform management strategies for patients with BBD in modern clinical settings.

Abstract Women at increased risk for breast cancer may benefit from taking risk-reducing medication (RRM) with tamoxifen (tam). Historical uptake of tam in women who qualify has been low. Recent studies have shown low-dose tam to have similar efficacy to standard dosing, with lower risk for adverse events. In this study, we aimed to evaluate uptake, adherence, and tolerability of low-dose tam in women at increased risk for breast cancer and those with ductal carcinoma in situ (DCIS). In this two-site prospective study, women who qualified for breast cancer RRM were offered participation and received consultation with a breast specialist for discussion of RRM rationale, benefits, side effects, and risks. Patients received baseline and 1-year follow-up surveys. A total of 41 patients consented for participation, and 31 completed 1-year follow-up. After initial consultation, 90% (n = 37) reported good/complete understanding of breast cancer risk. Of patients included in 1-year follow-up, 5 had DCIS, 13 had high-risk intraepithelial lesion, and 13 qualified based on Breast Cancer Risk Assessment Tool/International Breast Intervention Study calculation. Furthermore, 74% (n = 23) of patients reported that they took low-dose tam after consultation, with 78.2% (n = 18) of those still taking medication at 1 year. Patients who continued medication had higher estimated breast cancer risk compared with those who discontinued (International Breast Intervention Study 10-year risk, 12.7% vs. 7.6%; P = 0.027). All patients with DCIS initiated low-dose tam, and only one patient with DCIS had discontinued at 1 year. Uptake of low-dose tam after informed discussion is high. Adherence and tolerability at 1-year follow-up improved compared with those with traditional dosing of tam. Prevention Relevance: tam has been used extensively for breast cancer prevention in high-risk women. Historical uptake has been low because of concern for side effects and poor tolerability. Herein, we demonstrate that in the clinical setting, effective patient education and offering of a low-dose option can improve uptake in this high-risk population. See related Spotlight, p. 545

Abstract Background: Women at increased risk for breast cancer (BC) may benefit from taking prevention medication (PM) with tamoxifen (tam). Historical uptake to PMs for women who qualify has been low. Recent studies have shown baby tam (5mg/day) to have similar efficacy to standard dosing (20mg/day) with lower risk for adverse events (AEs) in women with DCIS or high risk intraepithelial lesions. Herein, we aimed to evaluate uptake, adherence, and tolerability of baby tam in women at increased risk for BC and those with DCIS. Methods: Women seen at the Mayo Clinic Breast Center in Minnesota or Florida who qualified for PM due to DCIS, high risk intraepithelial lesions (IELs) including LCIS and/or AH, or with increased risk based on validated BRCAT or IBIS model calculation (BCRAT 5 year risk ≥ 3% or IBIS 10 year risk ≥ 8%) were offered participation. All women received consultation with a breast specialist for discussion of PM rationale, benefits, side effects, and risks. Patients received baseline survey to assess understanding of their risk and role for PM and then 1 year follow-up survey to assess adherence and tolerability. Results: 41 patients consented for participation and 31 of those completed follow-up at 1 year.Median age of enrollment was 49 years. After initial consultation, 90% (n=37) reported good or complete understanding of BC risk. Of the 31 patients included in 1 year follow-up, 5 patients had DCIS, 13 had high-risk IELs, and 13 qualified based on BCRAT/IBIS calculation. Seventy-four percent (n= 23) of patients reported they took baby tam after consultation. No differences in age (p=0.89), education (p=0.13), or menopause status (p=0.11) between those who did and did not take medication were seen. Those who initiated baby tam were more likely to have DCIS or high risk IEL compared to those who did not (p < 0.001). Seventy-eight percent (n=18) of those who initiated baby tam were still taking medication at 1 year follow-up. Of patients who discontinued baby tam, all cited side effects as primary reason for discontinuation, with hot flashes (n=2), night sweats (n=2), and fatigue (n=2) being most common. Patients who continued medication had higher estimated BC risk compared to those who discontinued baby tam (IBIS 10 yr risk 12.7% vs 7.6%, p = 0.027). Patients with DCIS or high risk IEL were more likely to continue medication at 1 year compared to those patients who qualified for PM based on calculated BCRAT/IBIS score (p=0.05). Only 1 patient with DCIS and 1 patient with high-risk IEL discontinued baby tam at 1 year. Conclusions: Uptake to baby tam after informed discussion in patients who qualify is high, especially in those patients with high risk IELs or DCIS. Adherence and tolerability at 1 year follow-up is improved compared with traditional dosing of tam. Qualifying criteria for patients who did and did not take baby tamoxifen after informed consultation with breast specialist Citation Format: Lauren Cornell, Sandhya Pruthi, Karthik Ghosh, Klassen Christine, Pooja Advani. Improved uptake and adherence to prevention medication with use of baby tamoxifen in patients at high risk for breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS07-04.

Objective The purpose of this study was to determine self-reported knowledge, attitudes, prior experience, and perceived needs for the management of overweight and obese patients within a General Internal Medicine Practice. Patients and Methods An emailed cross-sectional survey was sent between June 20, 2019 and September 12, 2019 to 194 healthcare workers (93 primary care providers (PCPs) and 101 nurses) which focused on management of patients with weight issues. Results In total, 80 of the eligible 194 participants completed the survey (nurses = 42, PCPs = 38). Up to 87% were white, 74.7% female (74.7%). Most of the responders were either in the age group of 30’s (30%) or 50’s (30%). Among the responders, 48.8% reported some type of specialty training in weight management since their medical training with lectures being the most common form of training (36%). When asked about their interest in either weight management training or strategies to initiate weight conversations, 79% of the respondents reported an interest in education on weight management or strategies to initiate weight conversations, while 65.8% indicated they would be interested in both topics. Conclusion Our study suggests that healthcare workers have a self-reported need for further training in management of overweight and obese patients, irrespective of previous training in this area.

2 Background: Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but accurate personalized risk prediction is desirable to facilitate individual clinical management decisions. Currently used models provide poor BC risk prediction for women with AH. Our goal was to develop and validate an improved risk prediction model for women with AH. Methods: From a cohort of 13,538 women with benign breast disease from 1967-2001, pathology review confirmed 699 with AH. Clinical risk factors and histologic features of the tissue biopsy were recorded, and BC events were ascertained from study questionnaires, tumor registry, and review of medical records. Using a lasso approach, 23 variables were assessed for model inclusion. Lasso-identified features were then fit in a Cox regression model to estimate BC risk. Model discrimination was assessed with C-statistics in the model-building set and in a separate external validation set. Calibration was assessed by comparing observed to predicted breast cancer counts. Results: The model-building set comprised 699 women with 142 BC events (median follow-up 8.1 years), and the external validation set comprised 461 women with 114 BC events (median follow-up 11.4 years). The final model included three covariates: age at biopsy, age squared, and number of foci of AH. Model performance was good, with a C-statistic of 0.622 (SE = 0.027) in the model-building set and 0.594 (SE = 0.029) in the external validation set. The model is well-calibrated, with observed to expected numbers of BCs nearly equal across all post-biopsy follow-up years. Conclusions: We propose a new model for predicting BC risk in women with AH based on age at biopsy and number of foci of atypia. This model provides absolute risk estimates for women with AH, has good discriminatory ability, is well-calibrated, and validates in an external cohort.

Purpose Mammographic density and lobular involution are both significant risk factors for breast cancer, but whether these reflect the same biology is unknown. We examined the involution and density association in a large benign breast disease (BBD) cohort. Patients and Methods Women in the Mayo Clinic BBD cohort who had a mammogram within 6 months of BBD diagnosis were eligible. The proportion of normal lobules that were involuted was categorized by an expert pathologist as no (0%), partial (1% to 74%), or complete involution (≥ 75%). Mammographic density was estimated as the four-category parenchymal pattern. Statistical analyses adjusted for potential confounders and evaluated modification by parity and age. We corroborated findings in a sample of women with BBD from the Mayo Mammography Health Study (MMHS) with quantitative percent density (PD) and absolute dense and nondense area estimates. Results Women in the Mayo BBD cohort (n = 2,667) with no (odds ratio, 1.7; 95% CI, 1.2 to 2.3) or partial (odds ratio, 1.3; 95% CI, 1.0 to 1.6) involution had greater odds of high density (DY pattern) than those with complete involution (P trend < .01). There was no evidence for effect modification by age or parity. Among 317 women with BBD in the MMHS study, there was an inverse association between involution and PD (mean PD, 22.4%, 21.6%, 17.2%, for no, partial, and complete, respectively; P trend = .04) and a strong positive association of involution with nondense area (P trend < .01). No association was seen between involution and dense area (P trend = .56). Conclusion We present evidence of an inverse association between involution and mammographic density.