Ghosh, Karthik

Abstract Background Molecular breast imaging (MBI) has shown utility as a supplement to mammography in women with dense breasts. Background parenchymal uptake (BPU), which describes the level of Tc-99m sestamibi in fibroglandular tissue on MBI, varies among women with similar density. Higher BPU is associated with greater breast cancer risk. The goal of this work is to investigate the histological correlations of BPU that may explain this association with risk. Methods We compared histologic features of prospectively collected benign breast tissue biopsies from healthy women who had a region of dense tissue on mammography exhibiting one of the extreme categories of BPU on MBI: either photopenic or marked. Tissue composition of specimens was assessed by measuring area of epithelium, stroma, and fat and counting lobules. Lobular involution status was assessed by an expert pathologist as either none, partial, or complete. Ki-67 index and estrogen receptor-alpha expression were also assessed. Results Biopsies were performed in 48 women (mean age 54.9 years [SD 11.1 years]), including 20 with marked BPU and 28 with photopenic BPU. Women with marked BPU were younger (mean age 49.9 vs. 58.4 years, p = 0.004), had higher body mass index ( p = 0.01), and were more likely premenopausal ( p = 0.005). Marked BPU specimens had a higher proportion of epithelium (14.5% vs. 2.2%, p < 0.001), lower stromal content (44.8% vs. 84.2%, p = 0.005), similar fat (18.9% vs. 12.9%, p = 0.41), and greater lobule counts (15.5 vs. 6.3, p < 0.001) compared to photopenic specimens. Complete lobular involution was less frequent in marked tissue than in photopenic tissue (10.5% vs. 76%, p < 0.001). Ki-67 index was higher in marked BPU tissues (5.4% vs. 1.6%, p = 0.006), though the difference was attenuated after adjustment for epithelial area (p = 0.26). Estrogen receptor-alpha expression did not differ between marked and photopenic groups (25.6% vs. 28.4%, p = 0.12). Conclusions Marked BPU on MBI is associated with greater epithelial content, less lobular involution, and higher proliferative activity—features characteristic of tissue at elevated risk for malignant transformation. These findings suggest that BPU provides functional information beyond mammographic density, supporting its role as an imaging biomarker for breast cancer risk in women with dense breasts. Trial Registration: NCT01240278 and NCT01588834

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.

Objective: Multicancer Detection (MCD) tests, such as the GRAIL Galleri, offer a novel approach to cancer screening by detecting cancer-specific methylation patterns in cell-free DNA through a single blood sample. This study evaluated an 18-month implementation of MCD testing in a tertiary ambulatory internal medicine clinic. Patients and Methods: Between June 2022 and November 2023, 2244 asymptomatic (without symptoms attributed to cancer) patients underwent MCD testing. The study focused on operational workflows, patient and physician education, and diagnostic follow-up of positive results. Standardized materials, including electronic health record (EHR) workflows, FAQs, and diagnostic pathways, were developed to facilitate implementation. Challenges included managing false positives, patient anxiety, costs, and ethical considerations. Results: Of the 2244 patients tested, 17 (0.76%) had positive results, and 15 underwent further diagnostic evaluation. Cancer was confirmed in 11 (73.3%) patients, including cases of breast, colon, esophageal, lymphoma, ovarian, and pancreatic cancers. Four patients had no identifiable malignancy despite comprehensive work-up. Conclusions: MCD testing is feasible in routine clinical workflows, with 73% of positive cases yielding cancer diagnoses. While promising, further research is required to assess long-term outcomes, cost-effectiveness, and optimal implementation strategies of cancer interception in broader healthcare settings.

Introduction: The Undiagnosed Mass Clinic (UMC) at our institution is a clinical and research program created to address gaps in the early diagnostic phase of the cancer care continuum for patients with potential malignant neoplasms. All patients referred to the UMC are invited to participate in the UMC registry, which tracks operational and clinical metrics while maintaining a repository of blood and tissue specimens for future research. Methods: We conducted a retrospective cohort study of the first 100 patients enrolled in the UMC registry. We analyzed patient demographics, final diagnoses, and the time from initial consultation to final diagnosis. Results: Most participants were White (86%), non-Hispanic (93%), and married (72%). The mean (SD) age was 64 (13.9) years. The final diagnoses of the masses were categorized as malignant/neoplastic with malignant potential (n = 53), benign (n = 36), or requiring diagnostic surveillance (n = 10). The mean (SD) time from initial consultation to final diagnosis of malignant/neoplastic with malignant potential masses significantly improved from 37.4 (36.6) days for the first 50 participants to 17.3 (19.7) days for the next 50 participants ( P = .006). Conclusions: These initial insights from the UMC registry will help direct future efforts to improve the care of patients with potential malignant neoplasms.

Background: Latinas with mammographic dense breasts are at increased risk of breast cancer. This randomized controlled trial tests the effectiveness of three breast density (BD) educational approaches on adherence to subsequent mammography screening among Latinas receiving care at a Federally Qualified Health Center (FQHC). Measure(s): Adherence was ascertained using electronic health record and survey responses. Kaplan–Meier estimates of the time to subsequent mammogram were used to obtain adherence rates at 1- and 2-years post baseline mammogram. Cox modeling assessed whether adherence differed by patient characteristics or group assignment. Results: This analysis was limited to Latinas enrolled between October 27, 2016, and December 21, 2018 ( n = 946; 66.1% <50 years of age, 53.5% with dense breasts). Adherence rates at 1 year was 24.8% increasing to 51.7% by year 2. Latinas randomized to the Promotora + brochure + letter arm (hazard ratio [HR]: 1.09 [95% confidence interval [95% CI] 0.87 to 1.36]) or brochure + letter (HR: 1.03 [95% CI 0.82 to 1.29]) arm were not more likely to be adherent to subsequent mammography compared to the letter only arm ( p = 0.76) . Adjusting for age and study group, having more prior mammograms, being “extremely likely” to get an annual mammogram, and having more confidence to get an annual mammogram at baseline were significant drivers of subsequent adherence. Conclusion: Informational interventions targeting BD education alone are unlikely to significantly improve adherence to subsequent mammography among Latinas receiving care in FQHCs.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence. Although DFSP has a reported high rate of recurrence, metastasis is more uncommon. Fibrosarcomatous DFSP is an aggressive variant with an increased risk for local recurrence and metastasis. If achieving negative margins or resection is not feasible, radiation therapy or systemic treatment are options that may be considered by a multidisciplinary team. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline recommended treatment options available for DFSP.

Objectives: To identify patient characteristics, health concerns, and barriers to care based on overweight or obesity. Methods: A 50-question anonymous survey was administered to patients. Data were compared by body mass index (BMI). Results: Among 3976 distributed surveys, 899 were returned and 682 were analyzed. Most respondents were women (60%), White (94%), and married/partnered (65%) and had some college education (80%). Younger and unmarried persons had higher BMI ( P < .001). Concern for quality of life ( P < .001) and importance of lifestyle changes ( P = .006) increased with BMI, but confidence in making changes decreased as BMI increased ( P < .001). Perceived good health decreased with increasing BMI ( P < .001), whereas depression and other comorbid conditions increased. Self-esteem decreased and stigma increased with higher BMI (both P < .001). Weight discussions with clinicians ( P < .001) and belief that clinicians should be involved in weight management ( P = .002) increased with BMI, yet self-perception of being judged by clinicians also increased ( P < .001). As BMI increased, delays in seeking health care increased ( P < .001). Conclusions: This survey study highlights perceived health concerns and barriers to care among persons with overweight and obesity. With higher BMI, self-esteem decreased, and stigma, self-perception of poor health, perception of being judged by clinicians, and delay in seeking medical care increased.

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory disorder of the breast that is often underrecognized. The exact etiology and pathophysiology are unknown, but milk stasis is felt to play a role. Classically, this condition is noninfectious, but many cases are noted to be associated with Corynebacterium species. Most patients affected are parous women with a mean age of 35, and many have breastfed within five years of diagnosis. Patients typically present with a painful mass and symptoms of inflammation, and these features can sometimes mimic breast cancer. Biopsy is needed to make a definitive diagnosis, and noncaseating granulomas are found on core biopsy. Many patients have a waxing and waning course over a period of six months to two years. Goal of treatment is to avoid surgery given poor wound healing, high risk of recurrence, and poor cosmetic outcomes. Medical treatment is preferred and includes observation, antibiotics, steroids, and immune modulators such as methotrexate. In more recent years, topical and intralesional steroids have become the treatment of choice, with similar outcomes to oral steroids.