Interactive multidisciplinary pilot workshop to improve medical student perception of and interest in breast surgical oncology.

BACKGROUND: Exposure to breast surgical oncology (BSO) and the multidisciplinary management of patients with breast cancer is limited in medical school. The purpose of this study was to assess changes in student perceptions of BSO as a career following an interactive multidisciplinary workshop. METHODS: Pre-clinical medical students participated in a multidisciplinary, hands-on workshop, composed of breast radiology (BR), breast surgical oncology (BSO) and breast plastic reconstructive surgery (B-PRS). BR presented students screening and diagnostic breast imaging followed by hands-on ultrasound-guided biopsy on phantom simulators. BSO demonstrated lumpectomy, mastectomy, sentinel lymph node biopsy, and axillary lymph node dissections while B-PRS demonstrated oncoplastic techniques and autologous flap reconstruction with cadavers. Pre-and post-workshop surveys assessed student opinions on surgery and BSO. Results were compared using Wilcoxon Signed Rank, Wilcoxon Rank Sum, and Fisher's Exact. RESULTS: The workshop was attended by twenty-four students. There was a statistically significant increase in interest in BSO from 52% to 86% after the workshop (p = 0.003). The event improved understanding of the work and lifestyle in BSO for 79% (19/24). All students (100%) expressed interest to further explore BSO. The most common attractors to a career in BSO were impacts on patients' lives (N = 23), intellectual stimulation (N = 22), and earnings (N = 20). The most reported deterrents were lack of personal time (N = 18) and stress (N = 15). CONCLUSION: An interactive, anatomically based exposure to multidisciplinary breast cancer surgery improves medical student perception and interest in BSO. Medical schools should consider incorporating similar events to foster interest in BSO and other surgical subspecialties.

Advanced degrees, gender, and professional rank in surgery, disparities in academic medicine.

INTRODUCTION: Women comprise nearly half of all residents in training, yet there is a significant disparity of women in academic leadership. Surgical subspecialties are dominated by men in both percentages of physicians and leadership positions. We sought to examine the association of advanced non-medical degrees with academic rank and gender in academic surgery departments. METHODS: Faculty from 126 ACGME-accredited academic medical centers were analyzed to identify faculty gender as described in online biographical information, advanced non-medical degrees, academic rank, and additional leadership positions held. Descriptive statistics and logistic regression models were used for statistical analyses. RESULTS: 4536 surgeons were identified, 69.3% men, 27.3% female, and 3.3% unlisted. Female surgeons were more likely to hold advanced non-doctoral degrees than men (18.2% vs. 13.8%, p â€‹< â€‹0.002). Among those with advanced degrees, PhDs were held by 3.3% of women and 5.7% of men (p â€‹< â€‹0.001). Female surgeons were less likely to hold the rank of Professor than male surgeons (15.8% vs 30.3%, p â€‹< â€‹0.001), and more likely to hold the rank of Assistant Professor than male surgeons (51.9% vs 36.1%, p â€‹< â€‹0.001). This likelihood remained true when analyzing only surgeons with one or more advanced non-medical degrees. Men were more likely to be Chair of Surgery (3.0%), Division Chief (9.6%), and Research Chair (0.5%); compared to women (1.3%; 4.8%; 0.2%; p â€‹= â€‹0.001, <0.001, 0.21 respectively). CONCLUSIONS: There continues to be a significant male predominance in general surgery. Gender discrepancy is also seen in professional rank and academic title despite women holding more advanced degrees. Advanced degrees are currently considered academic qualifications, but this does not reflect surgical academic leadership roles or rank.

US tobacco companies selectively disseminated hyper-palatable foods into the US food system: Empirical evidence and current implications.

BACKGROUND AND AIMS: US tobacco companies owned leading US food companies from 1980 to 2001. We measured whether hyper-palatable foods (HPF) were disproportionately developed in tobacco-owned food companies, resulting in substantial tobacco-related influence on the US food system. DESIGN: The study involved a review of primary industry documents to identify food brands that were tobacco company-owned. Data sets from the US Department of Agriculture were integrated to facilitate longitudinal analyses estimating the degree to which foods were formulated to be hyper-palatable, based on tobacco ownership. SETTING AND CASES: United States Department of Agriculture data sets were used to identify HPF foods that were (n = 105) and were not (n = 587) owned by US tobacco companies from 1988 to 2001. MEASUREMENTS: A standardized definition from Fazzino et al. (2019) was used to identify HPF. HPF items were identified overall and by HPF group: fat and sodium HPF, fat and sugar HPF and carbohydrates and sodium HPF. FINDINGS: Tobacco-owned foods were 29% more likely to be classified as fat and sodium HPF and 80% more likely to be classified as carbohydrate and sodium HPF than foods that were not tobacco-owned between 1988 and 2001 (P-values = 0.005-0.009). The availability of fat and sodium HPF (> 57%) and carbohydrate and sodium HPF (> 17%) was high in 2018 regardless of prior tobacco-ownership status, suggesting widespread saturation into the food system. CONCLUSIONS: Tobacco companies appear to have selectively disseminated hyper-palatable foods into the US food system between 1988 and 2001.

Assessing Second Debridement Timing and Mortality in Necrotizing Soft Tissue Infections.

BACKGROUND: Patients with necrotizing soft tissue infection undergo an average of 4-5 debridements per hospital admission. Optimal timing for initial debridement is emergent. Second debridement is universally recommended to occur within 24 hours of the first, but no studies have successfully evaluated this time frame. Prior work has suggested that delays in second debridement are associated with increased mortality, and that few patients receive second debridement within 24 hours. METHODS: We performed a retrospective cohort study at a single center from 01/01/08 to 09/01/2021. The explanatory variable was whether the subject received second debridement within 24 hours of initial debridement. The primary outcome was in-hospital mortality. Baseline characteristics were collected. Subjects were stratified into 2 groups by time between first and second debridement: <24 and ≥24 hours. Variables were compared using Fisher's exact and Wilcoxon rank-sum tests. RESULTS: 77 patients met inclusion criteria. The median overall time to second debridement was 40 hours. 12 subjects received second debridement within 24 hours (15.6%). There was no difference in in-hospital mortality between the <24 (n = 3, 25.0%) and ≥24-hour second debridement groups (n = 4, 6.2%; P = .07). The 2 groups did not differ by secondary outcomes, including total number of debridements, ICU LOS, or wound closure. CONCLUSION: No difference in mortality was observed between subjects undergoing second debridement within 24 vs after 24 hours. Only 16% of subjects received second debridement within the recommended 24-hour time interval. Further study is required to identify the optimal timing of second debridement.

Evaluation of learning curve with Indocyanine Green (IcG) versus blue dye for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Indocyanine green (IcG) is an alternative to isosulfan blue (IB) for sentinel lymph node (SLN) mapping in breast cancer (BC). IcG carries improved cost and safety, but oncologic data upon implementation in practice is limited. We evaluated the learning curve defined as oncologic yield and operative (OR) time for IcG in SLN mapping in BC. METHODS: Retrospective review of patients >18 years with cTis-2 cN0 BC undergoing surgery first with SLN biopsy using IB or IcG. Analysis compared IB versus IcG across three time cohorts. RESULTS: Of 278 patients, 77 received IB and 201 received IcG. OR time was longer for IcG (p â€‹= â€‹0.022). There was no difference in oncologic yield between groups (p â€‹= â€‹0.35, p â€‹= â€‹0.61). CONCLUSIONS: Surgeons may be able to safely transition from IB to IcG for patients with early-stage breast cancer undergoing surgery first. Individuals should track their own data to confirm safety of the technique.

Breast Cancer-Related Lymphedema (BCRL) and Bioimpedance Spectroscopy: Long-Term Follow-Up, Surveillance Recommendations, and Multidisciplinary Risk Factors.

BACKGROUND: Early detection and intervention for breast cancer-related lymphedema (BCRL) significantly decreases progression to persistent BCRL (pBCRL). We aimed to provide long-term follow-up on our early detection with bioimpedance spectroscopy (BIS) and early home intervention demonstrating reduced pBCRL to guide surveillance recommendations. PATIENTS AND METHODS: In total, 148 female patients with breast cancer who had axillary lymph node dissection (ALND) from November 2014 to December 2017 were analyzed. Baseline BIS measurements and postoperative follow-up occurred every 3 months for 1 year, biannual for 1 year, and then annually. An elevated BIS triggered evaluation and initiation of at-home interventions with reassessment for resolution versus persistent BCRL (pBCRL). High-risk factors and timing were analyzed. RESULTS: Mean follow-up was 55 months, and 65 (44%) patients had an abnormal BIS. Of these, 54 (82%) resolved with home intervention. The overall pBCRL rate was 8%. Average time to first abnormal BIS was 11.7 months. None of the stage 0 patients (0/34) and only 5/25 (20%) of stage 1 patients had pBCRL. All of stage 2 and stage 3 patients (7/7) had pBCRL. pBCRL correlated with number of positive nodes, percentage of positive nodes, stage of lymphedema at diagnosis, and recurring abnormal BIS measurements (p < 0.05). CONCLUSIONS: We have shown that patients undergoing ALND with early BCRL identified by BIS who performed home interventions had an 8% pBCRL rate. Patients at high risk for pBCRL should have routine surveillance starting at 9 months postoperatively to identify an opportunity for early intervention.

Iodine Intake From Diet and Supplements and Urinary Iodine Concentration in a Cohort of Pregnant Women in the United States.

BACKGROUND: The DRI Estimated Average Requirement (EAR) in pregnancy for Iodine (I), an essential nutrient for fetal neurodevelopment, is 160 µg/d. Supplementation with 150 µg/d I/day is recommended during pregnancy, however, neither dietary intake or the combination of diet and supplement intake has been reported in US pregnant women. OBJECTIVE: Determine iodine intake from diet and supplements and iodine status in pregnancy by urinary iodine concentration in a large cohort of pregnant women. DESIGN: Pregnant women (n=750) completed the Diet History Questionnaire 2.0 from the National Institute of Cancer or multiple 24-hour recalls at baseline and identified their prenatal supplement(s). Dietary iodine intake was estimated using the USDA, FDA and ODS-NIH Database for the Iodine Content of Common Foods at enrollment, supplemental iodine intake throughout the study using content databases, and urinary iodine concentration (UIC) by the modified Sandell-Kolthoff reaction in samples collected between 14-20 weeks gestation (n=966). RESULTS: The median intake of iodine from diet was 108.8 µg/d, and 63% (473/750) were below the Estimated Average Requirement (EAR). Furthermore, 65% (529/818) took a supplement containing iodine, however, only 32% (259/818) took ≥150 µg/d. Median intake increased to 188.5 µg/d with the inclusion of I from supplements, however , 41% (380/925) remained below the EAR even after supplementation suggesting inadequate intake in nearly half of the cohort. A similar 48% (467/966) had UIC ≤150 µg/L. CONCLUSIONS: Assessment of iodine status by UIC and intake of iodine from diet and supplements support a high prevalence of iodine insufficiency during pregnancy in this large cohort of US women.

A Hands-On Surgical Event to Improve Medical Student Operating Room Confidence.

INTRODUCTION: The negative perceptions and lack of exposure to surgery and the operating room (OR) have been known to divert students away from surgical specialties. This study describes the impact of a surgical subspecialty exposure event (OR Essentials), combined with surgical faculty and M4 mentorship on preclinical medical students' confidence at an academic medical center. METHODS: OR essentials event teaches surgical skills to preclinical medical students through hands-on skill-based workshops in a simulated OR setting. Pre and postevaluations were administered to measure program impact. RESULTS: One hundred four preclinical medical students participated. Following OR essentials, students reported a significant increase in confidence in the OR (P < 0.0001) and in basic surgical skills (P < 0.0001). CONCLUSIONS: Early surgical exposure events like OR essentials provide opportunities to improve medical student confidence in the OR, which will hopefully support recruitment of future surgeons.

Trial of antibiotic restraint in presumed pneumonia: A Surgical Infection Society multicenter pilot.

BACKGROUND: Pneumonia is the most common intensive care unit-acquired infection in the trauma and emergency general surgery population. Despite guidelines urging rapid antibiotic use, data supporting immediate antibiotic initiation in cases of suspected infection are limited. Our hypothesis was that a protocol of specimen-initiated antibiotic initiation would have similar compliance and outcomes to an immediate initiation protocol. METHODS: We devised a pragmatic cluster-randomized crossover pilot trial. Four surgical and trauma intensive care units were randomized to either an immediate initiation or specimen-initiated antibiotic protocol for intubated patients with suspected pneumonia and bronchoscopically obtained cultures who did not require vasopressors. In the immediate initiation arm, antibiotics were started immediately after the culture regardless of patient status. In the specimen-initiated arm, antibiotics were delayed until objective Gram stain or culture results suggested infection. Each site participated in both arms after a washout period and crossover. Outcomes were protocol compliance, all-cause 30-day mortality, and ventilator-free alive days at 30 days. Standard statistical techniques were applied. RESULTS: A total of 186 patients had 244 total cultures, of which only the first was analyzed. Ninety-three patients (50%) were enrolled in each arm, and 94.6% were trauma patients (84.4% blunt trauma). The median age was 50.5 years, and 21% of the cohort was female. There were no differences in demographics, comorbidities, sequential organ failure assessment, Acute Physiology and Chronic Health Evaluation II, or Injury Severity Scores. Antibiotics were started significantly later in the specimen-initiated arm (0 vs. 9.3 hours; p < 0.0001) with 19.4% avoiding antibiotics completely for that episode. There were no differences in the rate of protocol adherence, 30-day mortality, or ventilator-free alive days at 30 days. CONCLUSION: In this cluster-randomized crossover trial, we found similar compliance rates between immediate and specimen-initiated antibiotic strategies. Specimen-initiated antibiotic protocol in patients with a suspected hospital-acquired pneumonia did not result in worse clinical outcomes compared with immediate initiation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Comparison of two validated instruments to measure financial hardship in cancer survivors: comprehensive score for financial toxicity (COST) versus personal financial wellness (PFW) scale.

PURPOSE: Financial distress and financial toxicity are recognized challenges in cancer survivorship. Financial toxicity includes both objective measures of hardship and subjective distress. We hypothesized that subjective financial distress is correlated to overall holistic financial toxicity. We compared two widely accepted instruments to measure financial distress and financial toxicity. METHODS: Patients in the follow-up phase of care at a single institution were surveyed regarding demographic and economic status. Financial toxicity was measured using the comprehensive score for financial toxicity-functional assessment of chronic illness (COST-FACIT) and financial distress using the personal financial wellness (PFW) scale. Surveys were analyzed for correlation and internal consistency. Patient score distributions were compared. Associations between survey scores and patient factors were assessed using multivariable linear regression models. RESULTS: A total of 116 patients were included. Scores from the COST-FACIT showed a strong correlation with PFW scores (r = 0.90, p < 0.0001). Scale reliability was high for both the COST-FACIT (α = 0.92) and PFW (α = 0.97) surveys. Score distributions exhibited left skew for both surveys, with 9.5% of patient scores falling in the worst quartile of possible scores on each respective survey. The strongest predictors of financial distress and financial toxicity included young age, lower monetary savings, lower household income, and less perceived social support during cancer treatment. CONCLUSIONS: The COST-FACIT measure of financial toxicity correlated strongly with PFW measure of financial distress. Although these instruments were designed to assess different concepts (financial distress vs financial toxicity), they gave strikingly similar results. Either instrument may be used as a meaningful patient-reported outcome for study of financial distress in cancer survivors. However, the COST-FACIT construct of financial toxicity does not appear to add additional information beyond financial distress.

Rethinking Routine Surgical Excision for all Radial Sclerosing Lesions of the Breast.

INTRODUCTION: The need for routine surgical excision of a radial sclerosing lesions (RSL) of the breast identified on percutaneous biopsy remains controversial, as contemporary upgrade rates are lower than historically cited. MATERIALS AND METHODS: A prospectively-maintained database of high-risk breast biopsies undergoing multidisciplinary review at a single institution was queried to identify cases of RSL from 2/2015 to 11/2020. Demographic, radiologic, and pathologic variables were summarized using frequencies and analyzed in association with RSL excision status using mixed-effects logistic regression or Fisher's exact tests. RESULTS: 217 RSL were identified, diagnosed at a mean age of 57 y. The median imaging size was 1.3 cm and the majority had estimated >50% of the target removed by core needle biopsy. 32.3% underwent surgical excision of the RSL biopsy site and 2/70 (2.9%) upgraded to ductal carcinoma in situ (DCIS) on final surgical pathology. Upgrade was significantly higher for atypical RSL (P = 0.02). None of the RSL (n = 60) without atypia who had undergone excision were upgraded. For those omitting surgical excision, there was no subsequent breast cancer diagnosis at the RSL site over a mean follow-up of 23 mo. CONCLUSIONS: Surgical excision may be omitted for RSL without atypia as this group has 0% risk of upgrade after multidisciplinary review.

Analysis of Research Productivity and Assessment of Geographical Region in the General Surgery Match: How Much is Enough?

OBJECTIVES: The number of publications of prospective surgical residents has steadily increased over the past decade as the emphasis on research output has become paramount. However, the reported data from the National Resident Matching Program (NRMP) does not discriminate amongst impact, author position, and region of matched residents. This study aimed to evaluate categorical general surgery postgraduate year 1 (PGY-1) residents' research productivity by programs' research impact and region of the United States and support the need for additional public data on research metrics of accepted applicants. We hypothesize that residents accepted to top quartile schools will have more total and first author publications and higher h-index compared to residents in the other quartiles, and research metrics would not differ amongst the regions. DESIGN: The Doximity Residency Navigator was used to sort general surgery programs based on research output, which was determined by the average h-index of residents. All 2021 matriculating PGY-1 categorical residents from the top two programs from each region and quartile that met study criteria were included in the analysis. Web of Science (WoS) citation database was used to collect prior to residency and current total publications, and the first, last, and corresponding author positions of these publications. Residents' h-index and various research metrics reported by WoS were recorded. Descriptive statistics were used to examine the association between quartile and region. SETTING: Categorical general surgery residency programs throughout the United States. PARTICIPANTS: Categorical PGY-1 general surgery residents. RESULTS: The median total number of publications prior to residency was 1 (IQR = 0-5). The median total number of first-author publications prior to residency was 0 (IQR = 0-1), and the current h-index was 0 (IQR = 0-2). The top quartile had more total and first author publications prior to residency, while the other quartiles had similar metrics. Each region had similar total publications and h-index. CONCLUSIONS: Research output is significant for applicants applying to top-quartile research programs compared to the other 3 quartiles and is relatively similar throughout all regions of the United States. Public data is limited to future applicants.

Rural-Urban Disparities in Health Access Factors Over Time: Implications for Cancer Prevention and Health Equity in the Midwest.

Purpose: Population-level environmental and socioeconomic factors may influence cancer burden within communities, particularly in rural and urban areas that may be differentially impacted by factors related to health care access. Methods: The University of Kansas (KU) Cancer Center serves a geographically large diverse region with 75% of its 123 counties classified as rural. Using County Health Rankings data and joinpoint regression, we examined trends in four factors related to the socioeconomic environment and health care access from 2009 to 2017 in rural and urban counties across the KU Cancer Center catchment area. Findings: The adult health uninsurance rate declined significantly in rural and urban counties across the catchment area (rural annual percent change [APC]=-5.96; 95% CI=[-7.71 to -4.17]; urban APC=-5.72; 95% CI=[-8.03 to -3.35]). Childhood poverty significantly decreased in rural counties over time (APC=-2.94; 95% CI=[-4.52 to -1.33]); in contrast, urban childhood poverty rates did not significantly change before 2012 (APC=3.68; 95% CI=[-15.12 to 26.65]), after which rates declined (APC=-5.89; 95% CI=[-10.01 to -1.58]). The number of primary care providers increased slightly but significantly in both rural and urban counties (APC=0.54; 95% CI=[0.28 to 0.80]), although urban counties had more primary care providers than rural areas (76.1 per 100K population vs. 57.1 per 100K population, respectively; p=0.009). Unemployment declined significantly faster in urban counties (APC=-10.33; 95% CI=[-12.16 to -8.47]) compared with rural counties (APC=-6.71; 95% CI=[-8.22 to -5.18]) (p=0.02). Conclusion: Our findings reveal potential disparities in systemic factors that may contribute to differences in cancer prevention, care, and survivorship in rural and urban regions.

Effect of prior radiation on stage, differentiation, and survival in bladder cancer.

PURPOSE: Clinically significant differences in radiation-related bladder tumors are not well-characterized, and survival analyses are needed. In this study, we aimed to utilize a national cancer database to evaluate the effect of prior radiation on tumor characteristics and survival in bladder cancer patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 9 database was queried to identify patients diagnosed with bladder cancer as a second malignancy. Patients having undergone radiation prior to developing bladder cancer were selected for comparative analysis. Logistic regression was used to generate odds ratios to evaluate differences in differentiation, stage, grade, and tumor size. Kaplan-Meier analysis and Cox non-proportional hazards regression models were used to assess the association between previous radiation and bladder cancer survival. RESULTS: A total of 25,408 patients were identified, of which 14,570 patients had sufficient data for analysis. Of these, 5968 (41.0%) received radiation for their primary malignancy. Prior radiation conferred a lower risk of developing moderately- or poorly-differentiated bladder tumors and muscle invasive or node-positive disease. An increased risk of squamous cell carcinoma was noted (OR 1.43, CI 1.06-1.93). Prior radiation led to an increased risk of bladder cancer-specific (HR 1.13, CI 1.03-1.24) mortality at 5 years. The greatest effect of prior radiation was an increased risk of bladder cancer-specific mortality for carcinoma in situ at 5 years (OR 2.37, CI 1.45-3.86). CONCLUSION: Prior radiation is associated with lower grade and stage of bladder tumors in addition to worse cancer-specific survival.

shinyOPTIK, a User-Friendly R Shiny Application for Visualizing Cancer Risk Factors and Mortality Across the University of Kansas Cancer Center Catchment Area.

PURPOSE: The University of Kansas Cancer Center (KU Cancer Center) recently developed a data warehouse to Organize and Prioritize Trends to Inform KU Cancer Center (OPTIK). The OPTIK database aggregates and standardizes data collected across the bistate catchment area served by the KU Cancer Center. To improve the usability of the OPTIK database, we developed shinyOPTIK, a user-friendly, interactive web application for visualizing cancer risk factor and mortality rate data across the KU Cancer Center Catchment area. METHODS: Data in the OPTIK database were first consolidated at the county level across the KU Cancer Center catchment area. Next, the shinyOPTIK development team met with the KU Cancer Center leadership to discuss the needs and priorities of the shinyOPTIK web application. shinyOPTIK was developed under the R Shiny framework and consists of a user interface (ui.R) and a web server (server.R). At present, shinyOPTIK can be used to generate county-level geographical heatmaps; bar plots of demographic, screening, and risk factors; and line plots to visualize temporal trends at different Rural-Urban Continuum Codes (RUCCs), rural-urban status, metropolitan, or county levels across the KU Cancer Center catchment area. RESULTS: Two examples, adult obesity prevalence and lung cancer mortality, are presented to illustrate how researchers can use shinyOPTIK. Each example is accompanied by post hoc visualizations to help explain key observations in terms of rural-urban disparities. CONCLUSION: Although shinyOPTIK was developed to improve understanding of spatial and temporal trends across the population served by the KU Cancer Center, our hope is that the description of the steps involved in the creation of this tool along with open-source code for our application provided herein will serve as a guide for other research centers in the development of similar tools.

The need to study rural cancer outcome disparities at the local level: a retrospective cohort study in Kansas and Missouri.

BACKGROUND: Rural residence is commonly thought to be a risk factor for poor cancer outcomes. However, a number of studies have reported seemingly conflicting information regarding cancer outcome disparities with respect to rural residence, with some suggesting that the disparity is not present and others providing inconsistent evidence that either urban or rural residence is associated with poorer outcomes. We suggest a simple explanation for these seeming contradictions: namely that rural cancer outcome disparities are related to factors that occur differentially at a local level, such as environmental exposures, lack of access to care or screening, and socioeconomic factors, which differ by type of cancer. METHODS: We conducted a retrospective cohort study examining ten cancers treated at the University of Kansas Medical Center from 2011 to 2018, with individuals from either rural or urban residences. We defined urban residences as those in a county with a U.S. Department of Agriculture Urban Influence Code (UIC) of 1 or 2, with all other residences defines a rural. Inverse probability of treatment weighting was used to create a pseudo-sample balanced for covariates deemed likely to affect the outcomes modeled with cumulative link and weighted Cox-proportional hazards models. RESULTS: We found that rural residence is not a simple risk factor but rather appears to play a complex role in cancer outcome disparities. Specifically, rural residence is associated with higher stage at diagnosis and increased survival hazards for colon cancer but decreased risk for lung cancer compared to urban residence. CONCLUSION: Many cancers are affected by unique social and environmental factors that may vary between rural and urban residents, such as access to care, diet, and lifestyle. Our results show that rurality can increase or decrease risk, depending on cancer site, which suggests the need to consider the factors connected to rurality that influence this complex pattern. Thus, we argue that such disparities must be studied at the local level to identify and design appropriate interventions to improve cancer outcomes.

A framework for personalized mammogram screening.

Breast cancer screening guidelines serve as crucial evidence-based recommendations in deciding when to begin regular screenings. However, due to developments in breast cancer research and differences in research interpretation, screening guidelines can vary between organizations and within organizations over time. This leads to significant lapses in adopting updated guidelines, variable decision making between physicians, and unnecessary screening for low to moderate risk patients (Jacobson and Kadiyala, 2017; Corbelli et al., 2014). For analysis, risk factors were assessed for patient screening behaviors and results. The outcome variable for the first analysis was whether the patient had undergone screening. The risk factors considered were age, marital status, education level, rural versus urban residence, and family history of breast cancer. The outcome variable for the second analysis was whether patients who had undergone breast cancer screening presented abnormal results. The risk factors considered were age, Body Mass Index, family history, smoking and alcohol status, hormonal contraceptive use, Hormone Replacement Therapy use, age of first pregnancy, number of pregnancies (parity), age of first menses, rural versus urban residence, and whether or not patients had at least one child. Logistic regression analysis displayed strong associations for both outcome variables. Risk of screening nonattendance was negatively associated with age as a continuous variable, age as a dichotomous variable, being married, any college education, and family history. Risk of one or more abnormal mammogram findings was positively associated with family history, and hormonal contraceptive use. This procedure will be further developed to incorporate additional risk factors and refine the analysis of currently implemented risk factors.

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036.

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.

Intra-individual Gene Expression Variability of Histologically Normal Breast Tissue.

Several studies have sought to identify novel transcriptional biomarkers in normal breast or breast microenvironment to predict tumor risk and prognosis. However, systematic efforts to evaluate intra-individual variability of gene expression within normal breast have not been reported. This study analyzed the microarray gene expression data of 288 samples from 170 women in the Normal Breast Study (NBS), wherein multiple histologically normal breast samples were collected from different block regions and different sections at a given region. Intra-individual differences in global gene expression and selected gene expression signatures were quantified and evaluated in association with other patient-level factors. We found that intra-individual reliability was relatively high in global gene expression, but differed by signatures, with composition-related signatures (i.e., stroma) having higher intra-individual variability and tumorigenesis-related signatures (i.e., proliferation) having lower intra-individual variability. Histological stroma composition was the only factor significantly associated with heterogeneous breast tissue (defined as > median intra-individual variation; high nuclear density, odds ratio [OR] = 3.42, 95% confidence interval [CI] = 1.15-10.15; low area, OR = 0.29, 95% CI = 0.10-0.86). Other factors suggestively influencing the variability included age, BMI, and adipose nuclear density. Our results underscore the importance of considering intra-individual variability in tissue-based biomarker development, and have important implications for normal breast research.