Routine Clinical Breast Examination Is a Low-Yield Practice Among Women at High Risk of Breast Cancer.

BACKGROUND: For women at increased risk of breast cancer, the National Comprehensive Cancer Network (NCCN) guidelines recommend clinical encounters every 6-12 months. While screening mammography has corresponded with a relative risk reduction in breast cancer mortality of approximately 20%, evidence validating clinical breast examination (CBE) as an efficacious screening modality is deficient. Our study aimed to assess the conventional merit of regular CBE for breast cancer detection among individuals at increased risk of breast cancer development. METHODS: Women > 18 years with documented high-risk encounters at Corewell Health West from 1 January 2018 to 31 December 22 were retrospectively reviewed. High-risk criteria included genetic predisposition, 5-year (> 1.7%) or lifetime (> 20%) Tyrer-Cuzick and/or Gail Model risk estimations, thoracic radiotherapy before age 30 years, lobular carcinoma in-situ, or atypical hyperplasia. Patients with a history of breast cancer or bilateral prophylactic mastectomy prior to 2018 were excluded. RESULTS: Of the 9171 cumulative high-risk encounters among 2493 women, only one breast cancer was detected by CBE. CBE resulted in 1 (0.04%) cancer diagnosis compared with 30 (1.2%) detected on screening imaging and 10 (0.4%) self-reported. Of the 30 image-detected cancers, 28 (93.3%) had no detectable clinical findings at the time of preoperative consultation. Self-reported and CBE-detected cancers were more likely to be of higher clinical stage compared with imaging-detected malignancies. CONCLUSIONS: The role of routine CBE as a cancer detection modality in the high-risk patient population appears to be limited. Telemedicine can be offered to individuals who have completed screening imaging but are unable to commit and/or are inconvenienced by in-person high-risk breast cancer assessments.

Pilot testing a patient decision aid as a strategy to reduce overtreatment for older women with early-stage breast cancer.

BACKGROUND: Despite national guidelines recommending omission of sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy (RT) in older women with early-stage, hormone receptor-positive (HR+) breast cancer, these practices persist. This pilot study assesses whether a decision aid can target patient-level determinants of low-value treatments. METHODS: We adapted and pilot-tested a decision aid in women ≥70 years old with early-stage HR â€‹+ â€‹breast cancer. Primary outcomes included acceptability and appropriateness of the decision aid. Secondary outcomes included treatment choice and satisfaction with decision. RESULTS: Twenty-three patients enrolled in the trial. 19 completed survey one; 16 completed survey two. Primary outcomes demonstrated that 84% of patients agreed or strongly agreed the aid was acceptable and appropriate. Secondary outcomes demonstrated that 19% of patients underwent SLNB (below pre-intervention baseline), and 85% received adjuvant RT (change not statistically significant). CONCLUSIONS: We demonstrate that a decision aid may effectively target patient-level factors contributing to overuse of low-value therapies.

A framework and process for community-engaged, mixed-methods cancer needs assessments.

PURPOSE: Community health needs assessments are required for most state and local public health agencies and non-profit hospitals. Typically based on community health improvement planning models, these assessments encompass overall community health and multiple diseases to inform program planning. National Cancer Institute (NCI)-designated Cancer Centers and community-based cancer-focused programs share the goal of reducing cancer burden in the catchment areas they serve. However, to date, no published models exist to guide cancer-specific needs assessments for a determined geographic area that can inform both public health and research initiatives. The purpose of this article is to outline a cancer needs assessment (CNA) framework and community-engaged, mixed-methods process, along with a case study of how we applied it in Kentucky. METHODS: We convened a steering committee of key organizational partners to provide input throughout the process. We developed a conceptual framework of multi-level determinants affecting cancer-related outcomes. We incorporated both quantitative and qualitative data gathered through a variety of means, including a novel application of group concept mapping to guide definition of priorities. RESULTS: The resulting CNA has helped guide strategic planning and priorities for Kentucky's Cancer Action Plan, Markey Cancer Center, state agencies, and community-based organizations. CONCLUSION: This framework and process can be used collaboratively by cancer center Community Outreach and Engagement offices, public health agencies, oncology programs, and community partners to plan impactful cancer control programs and research in their catchment areas. Universities can also use them to inform the planning of community engagement and health equity research efforts.

Ferritin heavy chain supports stability and function of the regulatory T cell lineage.

Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten-eleven translocation (TET) family of dioxygenases, and it involves a redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish that human and mouse TREG cells express Fe-regulatory genes, including that encoding ferritin heavy chain (FTH), at relatively high levels compared to conventional T helper cells. We show that FTH expression in TREG cells is essential for immune homeostasis. Mechanistically, FTH supports TET-catalyzed demethylation of CpG-rich sequences CNS1 and 2 in the FOXP3 locus, thereby promoting FOXP3 transcription and TREG cell stability. This process, which is essential for TREG lineage stability and function, limits the severity of autoimmune neuroinflammation and infectious diseases, and favors tumor progression. These findings suggest that the regulation of intracellular iron by FTH is a stable property of TREG cells that supports immune homeostasis and limits the pathological outcomes of immune-mediated inflammation.

Timing of mastectomy and the effect on the likelihood of outpatient surgery and cost savings in breast cancer patients.

BACKGROUND: Same-day discharge after mastectomy has potential patient- and hospital-level benefits; however, few data are available regarding factors affecting the likelihood of same-day discharge in order to address barriers. We sought to evaluate factors contributing to same-day discharge, focusing on the timing of mastectomy during the operative day. METHODS: We conducted a single-institution retrospective review of patients who underwent mastectomies for malignancy over a 3-y time frame. Clinicopathologic variables were collected along with a binary variable for mastectomy start time (morning versus afternoon). Our primary endpoint was rate of same-day discharge. A multivariable logistic regression model was constructed from significant univariate variables to determine independent predictors of same-day discharge. A secondary endpoint was a cost-utility analysis for morning versus afternoon start time, using hospital cost data. RESULTS: There were 451 patients included in the analysis. Factors associated with same-day discharge rate included the American Society of Anesthesiologists score, use of a preoperative regional anesthesia block, type of mastectomy performed, individual surgeon variation, and a morning start for the mastectomy. On multivariable analysis, morning start was a strong independent predictor of same-day discharge (odd ratio = 2.83; 95% CI, 1.75-4.60). The cost-utility analysis favored a morning start, with average cost savings of $550 per patient. CONCLUSION: Despite patient- and surgeon-specific variations, simple scheduling policies can improve same-day discharge rates after mastectomy, leading to improved hospital bed use and cost reduction.

The Effect of Wire Versus Magnetic Seed Localization on Lumpectomy Cavity Size.

PURPOSE: Our purpose was to assess whether an association exists between surgical localization technique and lumpectomy cavity size on radiation therapy planning computed tomography (CT) scan. METHODS AND MATERIALS: A single-institution retrospective review was conducted of women undergoing breast conserving surgery with wire or magnetic seed guided lumpectomy followed by adjuvant radiation therapy from 2018 to 2021. Patients of a surgeon only performing 1 localization technique or undergoing bracketed localization were excluded. The primary outcome was lumpectomy cavity size on simulation CT. Confounding due to imbalance in patient and tumor factors was addressed with overlap weights derived from a propensity score analysis and used in a weighted multivariable analysis. Secondary outcomes included positive margins, total pathologic volume, boost delivery, and boost modality. RESULTS: Of 617 women who received lumpectomy during the study period, 387 were included in final analysis. Tumors of patients undergoing seed localization were more likely unifocal, assessable by ultrasound, and smaller. Seed use rates ranged from 27.7% to 70.7% per surgeon. There was no difference in positive margins (6.4 vs 5.4%, P = .79) or second surgeries (9.4 vs 8.1%, P = .79) between groups. Close margin rates were similar for ductal carcinoma in situ (P = .35) and invasive carcinoma (P = .97). In unadjusted bivariable analyses, wire localization was associated with larger total pathology volume (P = .004), but localization technique showed no association with CT cavity volume (P = .15). After adjusting for potentially confounding variables, multivariable analysis failed to show an association between localization technique and either CT cavity (P = .35) or total path volume (P = .08). There was no difference in indicated-boost delivery (P = .15) or electron boost (P = .14) by localization technique. CONCLUSIONS: There was no significant difference in CT cavity size by localization technique, suggesting choice between surgical techniques does not impede radiation therapy boost delivery.

A Social Media-Based Public Health Campaign to Reduce Indoor Tanning in High-Risk Populations.

Introduction: Indoor tanning beds cause more than 450,000 new skin cancers each year, yet their use remains common, with a global indoor tanning prevalence of 10.4%. Social media provides an opportunity for cost-effective, targeted public health messaging. We sought to direct Instagram users at high risk of indoor tanning to accurate health information about the risks of indoor tanning and to reduce indoor tanning bed use. Methods: We disseminated a public health campaign on Instagram on April 6-27, 2022 with 34 video and still-image advertisements. We had 2 target audiences at high risk of indoor tanning: women aged 18-30 years in Kentucky, Nebraska, Ohio, or Tennessee interested in indoor tanning and men aged 18-45 years in California interested in indoor tanning. To evaluate the impact of the campaign, we tracked online metrics, including website visits, and conducted an interrupted time-series analysis of foot traffic data in our target states for all tanning salons documented on SafeGraph from January 1, 2018 to 3 months after the campaign. Results: Our indoor tanning health information advertisements appeared on Instagram feeds 9.1 million times, reaching 1.06 million individuals. We received 7,004 views of our indoor tanning health information landing page (Average Time on Page of 56 seconds). We did not identify a significant impact on foot traffic data on tanning salons. Conclusions: We show the successful use of social media advertising to direct high-risk groups to online health information about indoor tanning. Future research quantifying tanning visits before and after indoor tanning interventions is needed to guide future public health efforts.

Complexity of Data Displays in Prescription Drug Advertisements for Healthcare Providers.

BACKGROUND: Healthcare providers (HCPs) often encounter clinical trial results in the form of data displays in prescription drug promotions. Information conveyed in data displays vary in their presentation and complexity. This study describes characteristics of data displays in prescription drug advertising targeted to HCPs. METHODS: This study characterized the content of 140 data displays in 98 unique print advertisements from 2009 to present and identified in AdPharm, an online database of pharmaceutical advertisements. Two reviewers independently coded the advertisements for characteristics (κ = 0.85) including complexity, format, and quality. RESULTS: About one-third (32%) of the advertisements contained multiple data displays (range 2 to 6) and 44% showed clinical data from oncology trials; other disease domains were mental and behavioral health (14%), rheumatology and autoimmune disorders (8%), endocrinology (7%), cardiology (6%), infectious disease (6%), pulmonology and allergy (4%), and others (< 2% each). About one-half (51%) of displays were classified as "simple" which included "pseudographs" and basic tables or charts. "Complex" displays appeared as survival curves, line graphs, or bar graphs with complex features. Most complex displays included a comparator drug (90%), plain language restatement of the key finding (93%) and disclosure statements (91%) with additional study details, although their placement varied. Complex displays were of high quality, according to our selected indicators; our analysis found no data distortion or errors. CONCLUSION: Data displays in prescription drug advertising are often highly complex. Future research assessing understanding of data displays and the potentially beneficial effect of disclosures and other features is warranted.

Timing and necessity of staging imaging in clinical stage II cutaneous melanoma: Cost-effectiveness and clinical decision analysis.

BACKGROUND: Preoperative imaging in clinical stage II melanoma is not indicated per National Comprehensive Cancer Network (NCCN) guidelines but remains common in clinical practice. METHODS: Patients presenting with cutaneous clinical stage II melanoma from 2007 to 2019 were retrospectively reviewed. A clinical decision analysis with cost data was designed to understand ideal practice patterns in managing stage II melanoma, with pre-versus selective post-operative imaging as the initial decision node. RESULTS: There were 277 subjects included, and 143 underwent preoperative imaging (49.5%). This changed management (i.e. no surgery) in one patient (0.4%). Overall, 16 patients had additional findings on imaging (5.8%). Upfront surgery with selective postoperative imaging was a more cost-effective strategy than routine performance of preoperative imaging, with savings of $1677 per patient. CONCLUSION: Preoperative imaging is a low yield, costly approach for patients with clinical stage II melanoma with minimal impact on the decision to proceed with surgical management.

Surgeon Perspectives on Determinants of Same-Day Mastectomy: A Roadmap for Implementing Change.

BACKGROUND: Same-day discharge after mastectomy without immediate reconstruction (MwoR) has been shown to be safe, with improved patient satisfaction when compared with patients discharged 1 or more days after surgery. Nevertheless, only 16% of patients undergoing MwoR in Michigan are discharged on the day of surgery, with significant variation between facilities (3-88%). Our objective was to explore determinants of same-day discharge and offer strategies for broader implementation of this practice. METHODS: We conducted semi-structured interviews with surgeons performing MwoR across the state of Michigan. Recruitment utilized purposeful and snowball sampling methods. The Tailored Implementation in Chronic Disease (TICD) framework was used to inform the creation of the interview guide. Interviews were transcribed and then analyzed using directed content analysis guided by the TICD framework. Salient determinants were organized into patient, provider, and system-level factors. RESULTS: Participants (n = 26) included general surgeons, breast surgeons, and surgical oncologists. Most surgeons (n = 18, 69%) reported that they discharged fewer than 60% of patients the same day after MwoR. The most common barriers included patient knowledge at the patient level; awareness of evidence, surgeon dogma, and peer influence at the provider level; and team processes and operating room logistics at the system level. CONCLUSION: We identified surgeon-defined determinants of same-day discharge after MwoR. For the identified barriers, potential implementation strategies could include incorporation of preoperative drain teachings for patients, utilizing consensus statements and opinion leaders to disseminate evidence supporting same-day mastectomies, and conducting workshops with relevant stakeholders to establish consistent facility practice patterns among surgical teams.

Contemporary approaches to the axilla in breast cancer.

Over the past decade, axillary management in breast cancer has fundamentally shifted. The former notion that any degree of axillary nodal involvement warrants axillary lymph node dissection (ALND) has been challenged. Following publication of the ACOSOG Z0011 trial, national trends demonstrated significant reductions in ALND performance. Axillary radiotherapy in lieu of ALND is a consideration for select patients with a positive sentinel lymph node, while ongoing studies are investigating the role of adjuvant regional radiotherapy in women with positive nodes prior to neoadjuvant chemotherapy. Efforts toward de-escalation of axillary surgery continue to evolve, as do the indications for sentinel node biopsy omission in select subsets of patients. This review highlights the recent advances and neoteric approaches to local therapy of the axilla in breast cancer.

Prophylactic mastectomy and occult malignancy: Surgical and imaging considerations.

BACKGROUND: Sentinel node biopsy (SLNB) is not routinely recommended for patients undergoing prophylactic mastectomy (PM), yet omission remains a subject of debate among surgeons. A modern patient cohort was examined to determine occult malignancy (OM) incidence within PM specimens to reinforce current recommendations. METHODS: All PM performed over a 5-year period were retrospectively identified, including women with unilateral breast cancer who underwent synchronous or delayed contralateral PM or women with elevated cancer risk who underwent bilateral PM. RESULTS: The study population included 772 patients (598 CPM, 174 BPM) with a total of 39 OM identified: 17 invasive cancers (14 CPM, 3 BPM) and 22 DCIS (19 CPM, 3 BPM). Of the 86 patients for whom SLNB was selectively performed, 1 micrometastasis was identified. In the CPM cohort, risk of OM increased with age, presence of LCIS of either breast, or presence of a non-BRCA high-penetrance gene mutation, while preoperative magnetic resonance imaging was associated with lower likelihood of OM. CONCLUSIONS: Given the low incidence of invasive OM in this updated series, routine SLNB is of low value for patients undergoing PM. For patients with indeterminate radiographic findings, discordant preoperative biopsies, LCIS, or non-BRCA high-penetrance gene mutations, selective SLNB implementation could be considered.

Exploring Characteristics of Academic General Surgery Residency Applicants: A Group Concept-Mapping Approach.

OBJECTIVE: Holistic review, which emphasizes qualitative attributes over objective measures, has been proposed as a method for selecting candidates for surgical residency in order to improve diversity in graduate medical education, and, ultimately, the field of surgery. This study seeks to articulate desirable traits of applicants as a first-step in standardizing the holistic review process. DESIGN: Using Group Concept Mapping, a web-based mixed-methods participatory research methodology, residency selection committee members were asked to 1) list desirable characteristics of applicants, 2) group these into categories, 3) rate their importance to academic/clinical success on a 5-point Likert scale (1 = not at all important, 5 = extremely important), and 4) rate the degree to which each characteristic is feasible to assess on a 3-point Likert scale (1 = not at all feasible, 3 = very feasible). Grouped characteristics submitted to hierarchical cluster analysis depicted committee's consensus about desirable qualities/criteria for applicants. Bivariate scatter-plots and pattern-matching graphics demonstrated which of these criteria were most important and reliably assessed. SETTING: A single academic general surgery residency training program in Western Pennsylvania. PARTICIPANTS: Members of the selection committee for the UPMC General Surgery Residency program who had participated in at least 1 prior cycle of applicant selection. RESULTS: Desirable characteristics of highly qualified applicants into an academic general surgery residency were clustered into domains of 1) scholarly work and research, 2) grades/formal assessments, 3) program fit, 4) behavioral assets, and 5) aspiration. Behavioral assets, which was felt to be the most important to clinical and academic success were considered to be the least feasible to reliably assess. Within this domain, initiative, being self-motivated, intellectual curiosity, work ethic, communication skills, maturity and self-awareness, and thoughtfulness were viewed as most frequently reliably assessed from the application and interview process. CONCLUSIONS: High quality applicants possess several behavioral assets that faculty deem are important to academic and clinical success. Adapting validated metrics for assessing these assets, may provide a solution for addressing subjectivity and other challenges scrutinized by critics of holistic review.

Seminal vesicle fistula: a rare pathology in complicated Crohn's disease.

This case report describes a patient with complicated Crohn's disease who presented to a routine gastroenterology clinic complaining of increasing white discharge from a chronic perianal abscess. MRI of the perineum established the diagnosis of a seminal vesicle fistula connecting to the perianal skin. He was treated conservatively, with optimisation of his Crohn's disease medication regime. Seminal vesicle fistulation is a rare pathology.

Management of early stage HER2 positive breast cancer and increased implementation of axillary imaging to improve identification of nodal metastasis.

BACKGROUND AND OBJECTIVES: Given the significant benefit of targeted therapies for HER2+ breast cancer patients in both the neoadjuvant and adjuvant settings, it is critical to identify all eligible patients for these treatments. We sought to investigate cT1cN0 HER2+ patients to determine the rate of postsurgical nodal positivity, and to identify presurgical factors associated with nodal positivity. We hypothesize there is a subset of underdiagnosed HER2+ patients who would benefit from preoperative axillary imaging and inclusion in neoadjuvant chemotherapy regimens. METHODS: We performed a 10-year retrospective analysis of T1 HER2+ breast cancer patients. Clinicopathologic characteristics were evaluated based on surgical nodal data. RESULTS: We identified 38 patients with cT1cN0 HER2+ cancer. Of this cohort, 24% had positive lymph nodes on final pathology. High tumor grade (p = 0.035) on core needle biopsy and the presence of lymphovascular invasion (p = 0.0036) were associated with an increased likelihood of lymph node positivity. The majority (66%) of lymph node positive patients were clinically T1c. CONCLUSIONS: We identified a 24% nodal positivity rate in clinically node negative T1 HER2+ breast cancer patients. In particular, HER2+ patients with high-grade T1c cancers should undergo preoperative diagnostic axillary imaging to expand potential benefit from targeted therapies.