Towards defining morphologic parameters of normal parous and nulliparous breast tissues by artificial intelligence.

BACKGROUND: Breast terminal duct lobular units (TDLUs), the source of most breast cancer (BC) precursors, are shaped by age-related involution, a gradual process, and postpartum involution (PPI), a dramatic inflammatory process that restores baseline microanatomy after weaning. Dysregulated PPI is implicated in the pathogenesis of postpartum BCs. We propose that assessment of TDLUs in the postpartum period may have value in risk estimation, but characteristics of these tissues in relation to epidemiological factors are incompletely described. METHODS: Using validated Artificial Intelligence and morphometric methods, we analyzed digitized images of tissue sections of normal breast tissues stained with hematoxylin and eosin from donors ≤ 45 years from the Komen Tissue Bank (180 parous and 545 nulliparous). Metrics assessed by AI, included: TDLU count; adipose tissue fraction; mean acini count/TDLU; mean dilated acini; mean average acini area; mean "capillary" area; mean epithelial area; mean ratio of epithelial area versus intralobular stroma; mean mononuclear cell count (surrogate of immune cells); mean fat area proximate to TDLUs and TDLU area. We compared epidemiologic characteristics collected via questionnaire by parity status and race, using a Wilcoxon rank sum test or Fisher's exact test. Histologic features were compared between nulliparous and parous women (overall and by time between last birth and donation [recent birth: ≤ 5 years versus remote birth: > 5 years]) using multivariable regression models. RESULTS: Normal breast tissues of parous women contained significantly higher TDLU counts and acini counts, more frequent dilated acini, higher mononuclear cell counts in TDLUs and smaller acini area per TDLU than nulliparas (all multivariable analyses p < 0.001). Differences in TDLU counts and average acini size persisted for > 5 years postpartum, whereas increases in immune cells were most marked ≤ 5 years of a birth. Relationships were suggestively modified by several other factors, including demographic and reproductive characteristics, ethanol consumption and breastfeeding duration. CONCLUSIONS: Our study identified sustained expansion of TDLU numbers and reduced average acini area among parous versus nulliparous women and notable increases in immune responses within five years following childbirth. Further, we show that quantitative characteristics of normal breast samples vary with demographic features and BC risk factors.

Serum hormone levels and normal breast histology among premenopausal women.

PURPOSE: Breast terminal duct lobular units (TDLUs) are the main source of breast cancer (BC) precursors. Higher serum concentrations of hormones and growth factors have been linked to increased TDLU numbers and to elevated BC risk, with variable effects by menopausal status. We assessed associations of circulating factors with breast histology among premenopausal women using artificial intelligence (AI) and preliminarily tested whether parity modifies associations. METHODS: Pathology AI analysis was performed on 316 digital images of H&E-stained sections of normal breast tissues from Komen Tissue Bank donors ages ≤ 45 years to assess 11 quantitative metrics. Associations of circulating factors with AI metrics were assessed using regression analyses, with inclusion of interaction terms to assess effect modification. RESULTS: Higher prolactin levels were related to larger TDLU area (p < 0.001) and increased presence of adipose tissue proximate to TDLUs (p < 0.001), with less significant positive associations for acini counts (p = 0.012), dilated acini (p = 0.043), capillary area (p = 0.014), epithelial area (p = 0.007), and mononuclear cell counts (p = 0.017). Testosterone levels were associated with increased TDLU counts (p < 0.001), irrespective of parity, but associations differed by adipose tissue content. AI data for TDLU counts generally agreed with prior visual assessments. CONCLUSION: Among premenopausal women, serum hormone levels linked to BC risk were also associated with quantitative features of normal breast tissue. These relationships were suggestively modified by parity status and tissue composition. We conclude that the microanatomic features of normal breast tissue may represent a marker of BC risk.

Understanding benign breast disease and subsequent breast cancer in Hispanic white females; a step closer to evidence-based management.

Background While Hispanic white females (HW) have lower incidence of breast cancer (BC) than non-Hispanic white females (NHW), BC risk is unclear for HW females after benign breast disease (BBD). Methods We compared BBD characteristics and subsequent BC risk among HW and NHW females in New Mexico using a population-based collection of benign breast biopsies (1996-2007). BBD was categorized as non-proliferative disease (NPD), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). BC risk was assessed as absolute risk (AR) using cumulative incidence and relative risk (RR) by comparing the number of BC events in BBDs to non-BBD. Results This study included 3,684 HW and 6,587 NHW females with BBD. HW females had similar proportions of NPD (58.6%vs.54.3%), PDWA (21.4%vs.23.5%), and AH (3.6%vs.3.3%) as NHW. BC risk among all females with BBD was higher than population-based expected rates (RR=1.87) and was similar for HW and NHW subgroups (RR=1.99vs.1.84). As expected, BC risk increased with increasing BBD severity, both overall [RR=1.81 (NPD), 1.85 (PDWA) and 3.10 (AH)] and in the HW and NHW subgroups. Adjusted AR of BC at 5 years also increased with the severity of BBD (HW vs. NHW;NPD: 1.4 vs. 2.1%; PDWA: 1.5 vs. 2.7%; AH: 6 vs. 4.8%). Conclusions We found similar BC RRs and ARs in HW and NHW. Risk counseling should ensure that HW females receive breast cancer clinical management warranted by their similar absolute risks. Impact The present population-based provides evidence for clinical management of HW females with BBD for the prevention of BC.

Benign Breast Disease and Breast Cancer Risk in the Percutaneous Biopsy Era.

Importance: Benign breast disease (BBD) comprises approximately 75% of breast biopsy diagnoses. Surgical biopsy specimens diagnosed as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH) are associated with increasing breast cancer (BC) risk; however, knowledge is limited on risk associated with percutaneously diagnosed BBD. Objectives: To estimate BC risk associated with BBD in the percutaneous biopsy era irrespective of surgical biopsy. Design, Setting, and Participants: In this retrospective cohort study, BBD biopsy specimens collected from January 1, 2002, to December 31, 2013, from patients with BBD at Mayo Clinic in Rochester, Minnesota, were reviewed by 2 pathologists masked to outcomes. Women were followed up from 6 months after biopsy until censoring, BC diagnosis, or December 31, 2021. Exposure: Benign breast disease classification and multiplicity by pathology panel review. Main Outcomes: The main outcome was diagnosis of BC overall and stratified as ductal carcinoma in situ (DCIS) or invasive BC. Risk for presence vs absence of BBD lesions was assessed by Cox proportional hazards regression. Risk in patients with BBD compared with female breast cancer incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) program were estimated. Results: Among 4819 female participants, median age was 51 years (IQR, 43-62 years). Median follow-up was 10.9 years (IQR, 7.7-14.2 years) for control individuals without BC vs 6.6 years (IQR, 3.7-10.1 years) for patients with BC. Risk was higher in the cohort with BBD than in SEER data: BC overall (standard incidence ratio [SIR], 1.95; 95% CI, 1.76-2.17), invasive BC (SIR, 1.56; 95% CI, 1.37-1.78), and DCIS (SIR, 3.10; 95% CI, 2.54-3.77). The SIRs increased with increasing BBD severity (1.42 [95% CI, 1.19-1.71] for NP, 2.19 [95% CI, 1.88-2.54] for PDWA, and 3.91 [95% CI, 2.97-5.14] for AH), comparable to surgical cohorts with BBD. Risk also increased with increasing lesion multiplicity (SIR: 2.40 [95% CI, 2.06-2.79] for ≥3 foci of NP, 3.72 [95% CI, 2.31-5.99] for ≥3 foci of PDWA, and 5.29 [95% CI, 3.37-8.29] for ≥3 foci of AH). Ten-year BC cumulative incidence was 4.3% for NP, 6.6% for PDWA, and 14.6% for AH vs an expected population cumulative incidence of 2.9%. Conclusions and Relevance: In this contemporary cohort study of women diagnosed with BBD in the percutaneous biopsy era, overall risk of BC was increased vs the general population (DCIS and invasive cancer combined), similar to that in historical BBD cohorts. Development and validation of pathologic classifications including both BBD severity and multiplicity may enable improved BC risk stratification.

Community engaged research to measure the impact of COVID-19 on vulnerable community member's well-being and health : A mixed methods approach.

BACKGROUND: The COVID-19 pandemic has exacerbated existing income inequality and health disparities in the United States (US). The objective of this study was to conduct timely, community-engaged research to understand the disproportionate impact of the COVID-19 pandemic on historically under-resourced communities with the goal of improving health equity. The initiative focused on priorities identified by Community Health Needs Assessments (CHNA) conducted every 3 years per Federal funding requirements. These were access to healthcare, maternal/child health, obesity/food insecurity/physical activity, and mental health/addiction. METHODS: In the first three quarters of 2021, we developed and employed mixed methods in three simultaneous phases of data collection. In phase 1, we used purposive sampling to identify key informants from multiple stakeholder groups and conducted semi-structured interviews. In phase 2, we held focus groups with community members from historically marginalized demographics. In phase 3, we developed a survey using validated scales and distributed it to diverse communities residing in the geographic areas of our healthcare system across four states. CONCLUSION: Healthcare systems may use the methodology outlined in this paper to conduct responsive community engagement during periods of instability and/or crisis and to address health equity issues. The results can inform sustainable approaches to collaborate with communities to build resilience and prepare for future crises.

Adipose Cells Induce Escape from an Engineered Human Breast Microtumor Independently of their Obesity Status.

Introduction: Obesity is associated with increased breast cancer incidence, recurrence, and mortality. Adipocytes and adipose-derived stem cells (ASCs), two resident cell types in adipose tissue, accelerate the early stages of breast cancer progression. It remains unclear whether obesity plays a role in the subsequent escape of malignant breast cancer cells into the local circulation. Methods: We engineered models of human breast tumors with adipose stroma that exhibited different obesity-specific alterations. We used these models to assess the invasion and escape of breast cancer cells into an empty, blind-ended cavity (as a mimic of a lymphatic vessel) for up to sixteen days. Results: Lean and obese donor-derived adipose stroma hastened escape to similar extents. Moreover, a hypertrophic adipose stroma did not affect the rate of adipose-induced escape. When admixed directly into the model tumors, lean and obese donor-derived ASCs hastened escape similarly. Conclusions: This study demonstrates that the presence of adipose cells, independently of the obesity status of the adipose tissue donor, hastens the escape of human breast cancer cells in multiple models of obesity-associated breast cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-022-00750-y.

Predicting Cardiopulmonary Arrest with Digital Biomarkers: A Systematic Review.

(1) Background: Telemetry units allow the continuous monitoring of vital signs and ECG of patients. Such physiological indicators work as the digital signatures and biomarkers of disease that can aid in detecting abnormalities that appear before cardiac arrests (CAs). This review aims to identify the vital sign abnormalities measured by telemetry systems that most accurately predict CAs. (2) Methods: We conducted a systematic review using PubMed, Embase, Web of Science, and MEDLINE to search studies evaluating telemetry-detected vital signs that preceded in-hospital CAs (IHCAs). (3) Results and Discussion: Out of 45 studies, 9 met the eligibility criteria. Seven studies were case series, and 2 were case controls. Four studies evaluated ECG parameters, and 5 evaluated other physiological indicators such as blood pressure, heart rate, respiratory rate, oxygen saturation, and temperature. Vital sign changes were highly frequent among participants and reached statistical significance compared to control subjects. There was no single vital sign change pattern found in all patients. ECG alarm thresholds may be adjustable to reduce alarm fatigue. Our review was limited by the significant dissimilarities of the studies on methodology and objectives. (4) Conclusions: Evidence confirms that changes in vital signs have the potential for predicting IHCAs. There is no consensus on how to best analyze these digital biomarkers. More rigorous and larger-scale prospective studies are needed to determine the predictive value of telemetry-detected vital signs for IHCAs.

Changing the face of academic medicine: an equity action plan for institutions.

In recent years, there have been concerted efforts to better recruit, support, and retain diverse faculty, staff, and trainees in academic medicine. However, many institutions lack comprehensive and strategic plans to provide support to retain and recruit individuals from historically underrepresented groups. In this article, we itemize specific mechanisms through which institutions can support diverse individuals with the goal of improving inclusion and belonging in the workforce to better reflect the diversity of the intended patient and research participant population.

Key Stakeholder Perspectives of Community Engagement Efforts and the Impact of the Covid-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has disproportionally affected historically marginalized populations and their access to resources and healthcare. In times of crisis, authentic community engagement is more important than ever. This study was Phase 1 of a larger 3-phase study to conduct timely community-engaged research with community members to understand the disproportionate impact of COVID-19 on historically underserved communities. The objective of this work was to conduct key informant (KI) interviews (1) to understand community organizations perspectives about the role that large academic health centers play as they interface with community organizations to support their work, (2) to leverage KI's expertise to identify needs and assets within the community, and (3) to inform both Phase 2 (focus group qualitative research) and Phase 3 (survey) of the broader study. METHODS: A total of 24 key informants were identified through purposeful sampling and one-on-one semi-structured interviews were conducted across 4 states using video conferencing. RESULTS: Barriers to access and lack of transparency were highlighted as major issues requiring reform-in particular, aggressive billing practices and insurance barriers exacerbated local distrust of medical institutions. KIs recognized the health institution's support for testing and vaccination during the COVID-19 pandemic, but noted other significant gaps in care, especially regarding mental health support. Although communication with the health institution was consistent for some KIs, others experienced unsustained communication efforts that hindered cooperation and relationship building. CONCLUSIONS: Leaders in the community as key stakeholders can provide unique insights into the challenges and potential solutions required to promote health equity, and foster understanding between local communities and healthcare institutions.

Building a framework for inclusion in health services research: Development of and pre-implementation faculty and staff attitudes toward the Diversity, Equity, and Inclusion (DEI) plan at Mayo Clinic.

OBJECTIVE: To mitigate the impact of racism, sexism, and other systemic biases, it is essential for organizations to develop strategies to address their diversity, equity and inclusion (DEI) climates. The objective of this formative evaluation was to assess Mayo Clinic Department of Health Sciences Research (HSR) faculty and staff perceptions toward a proposed departmental DEI plan and to explore findings by diversity and professional subgroups. MATERIALS AND METHODS: Key plan components include recruitment and support for diverse individuals; training for all HSR employees and leaders; and a review system to capture diversity and inclusion feedback for leaders. Additional activities include building inclusion "nudges" into existing performance reviews. To assess pre-implementation beliefs about specific plan components, we polled attendees at a departmental staff meeting in July 2020. RESULTS: Overall, respondents (n = 162) commonly endorsed a blinded promotion review process and DEI training for all staff and leaders as most important. In contrast, respondents expressed less support for plan activities related to "nudges." However, attitudes among certain diversity or professional groups toward specific plan activities diverged from their non-diversity group counterparts. Qualitative feedback indicated awareness of the need to address DEI issues. DISCUSSION: Overall, HSR faculty and staff respondents conveyed support for the plan. However, some specific plan activities were perceived differently by members of certain diversity or professional subgroups. CONCLUSION: These findings present a DEI framework on which other institutions can build and point to future directions for how DEI activities may be differentially perceived by impacted faculty and staff.

Development of novel home-based tampon sampling for endometrial cancer: findings from community-based focus groups with Black and White women.

Novel endometrial cancer (EC) early-detection approaches may reduce racial disparities in mortality. We conducted six community-based focus groups with White and Black women (N = 57 participants) in February-March 2020 to explore acceptability of a home-based tampon sampling approach for EC. Participants also completed a survey. Data were analyzed using qualitative content analysis. Awareness of EC and risk factors was low. Acceptability regarding home sampling was high, but participants expressed concerns about instruction complexity and potential risks. Black women reported lower comfort with tampons. Increasing EC awareness, self-efficacy, and familiarization with tampons would advance prospects for at-home sample collection for EC testing.