Hormone therapy in women with benign breast disease - What little is known and suggestions for clinical implementation.

Benign breast disease encompasses a spectrum of lesions within the breast. While some lesions pose no increase in risk, others may elevate the likelihood of developing breast cancer by four- to five-fold. This necessitates a personalized approach to screening and lifestyle optimization for women. The menopausal transition is a critical time for the development of benign breast lesions. Increased detection can be attributed to the heightened precision and utilization of screening mammography, with or without the use of supplemental imaging. While it is widely acknowledged that combined hormone therapy involving estrogen and progesterone may elevate the risk of breast cancer, data from the Women's Health Initiative (WHI) indicates that estrogen-alone therapies may actually reduce the overall risk of cancer. Despite this general understanding, there is a notable gap in information regarding the impact of hormone therapy on the risk profile of women with specific benign breast lesions. This review comprehensively examines various benign breast lesions, delving into their pathophysiology and management. The goal is to enhance our understanding of when and how to judiciously prescribe hormone therapy, particularly in the context of specific benign breast conditions. By bridging this knowledge gap, the review provides valuable insights into optimizing healthcare strategies for women with benign breast disease, and offers a foundation for more informed decision-making regarding hormone therapy.

Rare Presentation of Papillary Carcinoma Within a Sentinel Lymph Node in a Patient With Ductal Carcinoma in Situ of the Breast: A Challenging but Useful Case Report Discussion Regarding Displacement or True Metastasis?

Papillary carcinoma of the breast is a rare histologic subtype of invasive breast cancer. In contrast, ductal carcinoma in situ (DCIS) is a noninvasive, nonobligate precursor to invasive mammary carcinoma, confined within the terminal duct lobular unit of the breast and surrounded by an intact myoepithelial cell layer at the stromal/epithelial interface. We present an unusual case in which a patient with only DCIS of the breast exhibited papillary carcinoma within a sentinel lymph node, leading to questions about the origin of the lymph node lesion-whether it represents a true metastasis or iatrogenic displacement during diagnostic procedures. This case underscores the diagnostic challenges and clinical implications associated with such rare presentations.

Encapsulated papillary carcinoma of the breast: A case report.

Breast malignancies diagnosed from screening mammography most commonly present as a new or enlarging lesion at the time of diagnosis. We present the unusual case of an encapsulated papillary carcinoma that demonstrated decreasing size on mammogram over several subsequent years. We review the unique imaging and histologic findings of papillary carcinoma that make this imaging conundrum possible.

Association of Neurohormonal Antagonists on Incident Cardiotoxicity in Patients With Breast Cancer.

Cardiovascular disease is the leading cause of mortality among breast cancer survivors. Anthracyclines and trastuzumab have been associated with an increased risk of cardiotoxicity, requiring close follow-up for signs of clinical heart failure or asymptomatic left ventricular systolic dysfunction. Whether neurohormonal antagonism with angiotensin-converting enzyme inhibitor (ACE-I), angiotensin receptor blockers (ARBs), or ß-blockers can prevent the development of chemotherapy-induced cardiomyopathy in this population remains unknown. We studied 459 women who were diagnosed with breast cancer at our medical center from January 2014 to December 2021 and evaluated baseline characteristics, oncologic treatment, and outcomes. The primary end point was the development of cardiotoxicity, defined as symptomatic decline in ejection fraction of ≥5% below 55% or an asymptomatic decline of ≥10% after treatment with chemotherapy. Patients who were exposed to neurohormonal antagonists were more likely to have hypertension, hyperlipidemia, and diabetes. There was an increased risk of cardiotoxicity noted for patients who were older (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.01 to 1.1), smokers within the past 10 years (HR 2.54, 95% CI 1.41 to 4.6), or who received a combination of both trastuzumab and anthracycline therapy (HR 2.52, 95% CI 1.01 to 6.3). Over a median follow-up of 12 months, there were no significant protective benefits noted for patients who were taking ACE-I/ARBs (HR 0.49, 95% CI 0.17 to 1.4), ß-blockers (HR 0.50, 95% CI 0.16 to 1.6), or both (HR 1.30, 95% CI 0.44 to 3.9). In conclusion, previous use of ACE-I/ARBs and ß-blockers, separately or in combination, was not associated with a reduction in the development of cardiotoxicity in patients receiving anthracycline or trastuzumab therapies. Older age, smoking, and combination chemotherapy were found to be associated with an increased risk.

Upregulation of Endothelin-1 May Predict Chemotherapy-Induced Cardiotoxicity in Women with Breast Cancer.

As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving anthracycline-based chemotherapy followed by trastuzumab are at risk for CIC. Previous research evaluating whether clinical biomarkers predict cardiotoxicity has been inconsistent. Recently, angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) have been shown to play a role in breast tumor growth. We evaluated ATR1 and ET1 expression in breast cancer tissue and its association with CIC. A total of 33 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were analyzed by immunohistochemistry (IHC) and qRT-PCR. We found that ET1 expression was increased in patients with an LVEF ≤ 50% (p = 0.032) with a lower LVEF correlating with higher ET1 expression (r = 0.377, p = 0.031). In patients with a change in LVEF of greater than 10%, greater ET1 expression was noted compared to those without a change in LVEF (p = 0.017). Increased ET1 expression in breast tumor tissue is associated with reduced LVEF. Future studies need to examine whether ET1 may be a tissue biomarker that helps predict the risk of developing CIC in women with breast cancer.

Assessment of Commercial Off-the-Shelf Tissue Adhesives for Sealing Military-Relevant Corneal Perforation Injuries.

INTRODUCTION: Open-globe ocular injuries have increased in frequency in recent combat operations due to increased use of explosive weaponry. Unfortunately, open-globe injuries have one of the worst visual outcomes for the injured warfighter, often resulting in permanent loss of vision. To improve visual recovery, injuries need to be stabilized quickly following trauma, in order to restore intraocular pressure and create a watertight seal. Here, we assess four off-the-shelf (OTS), commercially available tissue adhesives for their ability to seal military-relevant corneal perforation injuries (CPIs). MATERIALS AND METHODS: Adhesives were assessed using an anterior segment inflation platform and a previously developed high-speed benchtop corneal puncture model, to create injuries in porcine eyes. After injury, adhesives were applied and injury stabilization was assessed by measuring outflow rate, ocular compliance, and burst pressure, followed by histological analysis. RESULTS: Tegaderm dressings and Dermabond skin adhesive most successfully sealed injuries in preliminary testing. Across a range of injury sizes and shapes, Tegaderm performed well in smaller injury sizes, less than 2 mm in diameter, but inadequately sealed large or complex injuries. Dermabond created a watertight seal capable of maintaining ocular tissue at physiological intraocular pressure for almost all injury shapes and sizes. However, application of the adhesive was inconsistent. Histologically, after removal of the Dermabond skin adhesive, the corneal epithelium was removed and oftentimes the epithelium surface penetrated into the wound and was adhered to inner stromal tissue. CONCLUSIONS: Dermabond can stabilize a wide range of CPIs; however, application is variable, which may adversely impact the corneal tissue. Without addressing these limitations, no OTS adhesive tested herein can be directly translated to CPIs. This highlights the need for development of a biomaterial product to stabilize these injuries without causing ocular damage upon removal, thus improving the poor vision prognosis for the injured warfighter.

Transcorneal Freezing in Aged Rabbits as a Platform for Evaluating Corneal Endothelial Cell Therapeutics.

PURPOSE: Transcorneal freezing is a common technique used in rabbits to induce damage to the corneal endothelium. Previous studies have been performed with a range of freezing temperatures, times, and rabbit ages. Here, we aimed to characterize the aged rabbit endothelium after transcorneal freezing to establish an innate corneal endothelial cell regrowth rate and propose it as a mechanism for evaluation of therapeutic efficacy in rabbit models. METHODS: Central corneas of anesthetized New Zealand White rabbits (n=3) aged 18-24 months were exposed to nitrous oxide cooled probes for 30 seconds. Animals were assessed by in vivo confocal microscopy, applanation tonometry, specular microscopy, optical coherence tomography, and histology. The contralateral eye acted as a control. Images were taken immediately before and after injury and on days 2, 4, 7, 11, and 14. RESULTS: Following transcorneal freezing, there was a significant decrease in corneal endothelium density and a temporary increase in corneal thickness. Endothelial density decreased by 95% immediately after injury compared to controls and showed linear recovery over 14 days, reaching a 38% reduction by day 14. There was a significant increase in pleomorphism across all time points post-injury. Conversely, corneal thickness increased two days post injury but recovered at all later time points. Intraocular pressure was not affected throughout. CONCLUSIONS: This corneal endothelium injury platform is ideal for injury and therapeutic research as it can be rapidly performed, and has minimal impact on corneal thickness and intraocular pressure. Due to innate rabbit endothelial regrowth, it is vital to establish corneal endothelial recovery rate before evaluating therapeutics for efficacy in this model system.

Evaluating sensitivity and specificity of the Biomeme Franklin™ three9 real-time PCR device and SARS-CoV-2 go-strips assay using clinical samples.

We evaluated the sensitivity and specificity of the Biomeme Franklin™ three9 Real-Time PCR Thermocycler and Biomeme SARS-CoV-2 Go-Strips in the detection of SARS-CoV-2. The Biomeme Franklin™ three9 platform is a portable, battery-operated system that could be used in remote settings. We assessed performance of the Biomeme SARS-CoV-2 detection system at a wide range of viral concentrations, examined cross-reactivity of the SARS-CoV-2 Go-Strips against several near-neighbor respiratory pathogens, and evaluated agreement against the BioFire® Respiratory Panel 2.1 in four clinical sample types. Our data indicate the Biomeme Go-Strips can reliably detect SARS-CoV-2 at a concentration of 4.2 × 103 copies/mL. No cross reactivity of the Go-Strips targets was detected against any of the tested near-neighbor respiratory pathogens. Cohen's kappa statistics ranged from 0.68 to 0.92 between results from the Biomeme SARS-CoV-2 Go-Strips and the BioFire® Respiratory Panel 2.1 in all the different sample types. Compared to the BioFire® Respiratory Panel 2.1, the Biomeme SARS-CoV-2 Go-Strips demonstrated statistically significantly lower sensitivity in 3 out of 5 sample types. Overall, our study demonstrates the Biomeme Franklin™ three9 used with the SARS-CoV-2 Go-Strips is an effective system for the detection of SARS-CoV-2 that could potentially be used in a remote or austere environment.

Asymptomatic coronavirus disease 2019 mimicking metastatic breast cancer on positron emission tomography/computed tomography imaging.

A 55-year-old asymptomatic woman with newly diagnosed, locally advanced breast cancer undergoing routine staging with 2-deoxy-2[18F]fluoro-d-glucose positron emission tomography/computed tomography was found to have multiple hypermetabolic pulmonary nodules on imaging that were concerning for metastatic disease. However, further workup with dedicated chest computed tomography imaging demonstrated multiple bilateral, peripheral nodular lesions with peripheral ground-glass opacity, predominantly in the lower lung zone, that were suspicious for coronavirus disease 2019. The patient ultimately was diagnosed with coronavirus disease 2019 based on detection of viral ribonucleic acid via polymerase chain reaction. Follow-up chest computed tomography scan obtained after 27 days showed complete resolution of the lung lesions. In the setting of a global pandemic, a high index of suspicion for coronavirus disease 2019 in cancer patients is warranted, not only to enable early identification and treatment of a potentially aggressive infection but also to prevent misdiagnosis of metastatic disease.

Pre-diagnosis major life stressors and breast cancer outcomes.

PURPOSE: While the association between diagnosis of breast cancer and post-diagnosis psychological distress has been well documented, data regarding pre-diagnosis psychological distress in the breast cancer population are limited. Here, we assessed pre-diagnosis major life stressors and breast cancer outcomes, namely stage of disease and choice of surgery, in a single-center population. METHODS: Patients with newly diagnosed clinical stage 0-3 breast cancer seen at Mayo Clinic Florida between June 11, 2018, and October 7, 2019, were administered voluntary telephone surveys to assess major life stressors during the 24 months preceding their cancer diagnosis. Subsequent clinical outcomes of cancer stage at diagnosis and surgical treatment were obtained through retrospective chart review. Study subjects who had experienced major life stressors and those who had not were compared using Chi-square tests. RESULTS: Of 222 patients who were included, 51.3% reported experiencing a major life event before breast cancer diagnosis. 43.9% of these patients endorsed family-related stress. 21.1% had experienced multiple stressors. 1.8% described financial stress. Although more patients in the group with pre-diagnosis stress had carcinoma in situ (21.1% versus 13.0%, p = 0.11) and fewer had stage T1/T2 disease (64% versus 73.1%, p = 0.14) than in the group without stress, these differences were not statistically significant. More patients with pre-diagnosis stress chose mastectomy (34.2% versus 22.2%, p = 0.048). CONCLUSIONS: Psychological distress is prevalent prior to breast cancer diagnosis and may merit early intervention. While additional study in diverse populations is needed, current data suggest possible associations between pre-diagnosis psychological distress and surgical decision making, specifically mastectomy.

Mental Health and Chemical Dependency Services at US Cancer Centers.

BACKGROUND: It is standard of care and an accreditation requirement to screen for and address distress and psychosocial needs in patients with cancer. This study assessed the availability of mental health (MH) and chemical dependency (CD) services at US cancer centers. METHODS: The 2017-2018 American Hospital Association (AHA) survey, Area Health Resource File, and Centers for Medicare & Medicaid Services Hospital Compare databases were used to assess availability of services and associations with hospital-level and health services area (HSA)-level characteristics. RESULTS: Of 1,144 cancer centers surveyed, 85.4% offered MH services and 45.5% offered CD services; only 44.1% provided both. Factors associated with increased adjusted odds of offering MH services were teaching status (odds ratio [OR], 1.76; 95% CI, 1.18-2.62), being a member of a hospital system (OR, 2.00; 95% CI, 1.31-3.07), and having more beds (OR, 1.04 per 10-bed increase; 95% CI, 1.02-1.05). Higher population estimate (OR, 0.98; 95% CI, 0.97-0.99), higher percentage uninsured (OR, 0.90; 95% CI, 0.86-0.95), and higher Mental Health Professional Shortage Area level in the HSA (OR, 0.99; 95% CI, 0.98-1.00) were associated with decreased odds of offering MH services. Government-run (OR, 2.85; 95% CI, 1.30-6.22) and nonprofit centers (OR, 3.48; 95% CI, 1.78-6.79) showed increased odds of offering CD services compared with for-profit centers. Those that were members of hospital systems (OR, 1.61; 95% CI, 1.14-2.29) and had more beds (OR, 1.02; 95% CI, 1.01-1.03) also showed increased odds of offering these services. A higher percentage of uninsured patients in the HSA (OR, 0.92; 95% CI, 0.88-0.97) was associated with decreased odds of offering CD services. CONCLUSIONS: Patients' ability to pay, membership in a hospital system, and organization size may be drivers of decisions to co-locate services within cancer centers. Larger organizations may be better able to financially support offering these services despite poor reimbursement rates. Innovations in specialty payment models highlight opportunities to drive transformation in delivering MH and CD services for high-need patients with cancer.

Amniotic membrane allografts maintain key biological properties post SCCO2 and lyophilization processing.

Amniotic membrane (AM) has been shown to enhance corneal wound healing due to the abundance of growth factors, cytokines, and extracellular matrix (ECM) proteins inherent to the tissue. As such, AM has garnered widespread clinical utility as a biological dressing for a number of ophthalmic and soft tissue applications. The preparation, sterilization, and storage procedures used to manufacture AM grafts are extremely important for the conservation of inherent biological components within the membrane. Current processing techniques use harsh chemicals and sterilization agents that can compromise the fundamental wound healing properties of AM. Furthermore, commercially available cryopreserved AM products require specific storage conditions (e.g., ultra-low freezers) thereby limiting their clinical availability in austere environments. Supercritical carbon dioxide (SCCO2) technology allows for the sterilization of biological tissues without the resulting degradation of integral ECM proteins and other factors often seen with current tissue sterilization processes. With this study we demonstrate that lyophilized AM, sterilized using SCCO2, maintains similar biochemical properties and biocompatibility as that of commercially available AM products requiring specialized cold storage conditions.

An Open-Globe Porcine Injury Platform for Assessing Therapeutics and Characterizing Biological Effects.

Open-globe injuries can result in permanent vision loss, partly due to extended delays between injury and medical intervention. Even with early intervention, the management of open-globe injuries remains a challenge for ophthalmologists, mostly due to inadequate or suboptimal current therapies. To aid in the development of novel therapeutics and track toxicological and pathophysiological changes, this article details an open-globe injury platform capable of inducing injuries in enucleated porcine eyes. The injury platform relies on a high-speed solenoid device to mimic explosive injury scenarios, allowing for large, complex injury shapes and sizes that are often observed in casualties and are more difficult to treat. The system can be implemented with precise computer control of the injury mechanism to allow for more complex setups. Also, the system can make use of real-time intraocular pressure measurement to track changes during injury induction and to assess therapeutic efficacy for restoring intraocular pressure and the integrity of the eye. These protocols will assist with implementation of the injury model in prospective laboratories seeking to develop therapeutics or studying biological changes that occur from this type of traumatic injury. Published 2020. U.S. Government. Basic Protocol 1: Preparing gelatin molds and porcine eye tissue Basic Protocol 2: Creating an open-globe injury using a solenoid device Alternate Protocol 1: Constructing a computer-controlled system for open-globe injury Alternate Protocol 2: Constructing a pressure measurement system for tracking intraocular pressure Support Protocol 1: Assessing ocular compliance in porcine eyes Support Protocol 2: Assessing outflow rate from the anterior chamber Support Protocol 3: Assessing burst pressure in porcine eyes.

Development and Characterization of a Benchtop Corneal Puncture Injury Model.

During recent military operations, eye-related injuries have risen in frequency due to increased use of explosive weaponry which often result in corneal puncture injuries. These have one of the poorest visual outcomes for wounded soldiers, often resulting in blindness due to the large variations in injury shape, size, and severity. As a result, improved therapeutics are needed which can stabilize the injury site and promote wound healing. Unfortunately, current corneal puncture injury models are not capable of producing irregularly shaped, large, high-speed injuries as seen on the battlefield, making relevant therapeutic development challenging. Here, we present a benchtop corneal puncture injury model for use with enucleated eyes that utilizes a high-speed solenoid device suitable for creating military-relevant injuries. We first established system baselines and ocular performance metrics, standardizing the different aspects of the benchtop model to ensure consistent results and properly account for tissue variability. The benchtop model was evaluated with corneal puncture injury objects up to 4.2 mm in diameter which generated intraocular pressure levels exceeding 1500 mmHg. Overall, the created benchtop model provides an initial platform for better characterizing corneal puncture injuries as seen in a military relevant clinical setting and a realistic approach for assessing potential therapeutics.

Current Management and Treatment Options for Breast Pain.

Breast pain is a commonly experienced symptom in women of all ages and can significantly impact quality of life. Fear of cancer prompts many patients to report their pain, although risk for malignancy is low in the absence of a palpable mass or other abnormal finding on breast examination. All patients with breast pain should have a thorough history and physical examination to determine if diagnostic imaging is indicated. Management of breast pain without anatomic or radiographic abnormalities depends on pain type and severity. Often, no intervention is required. However, for women with pain that adversely impacts daily living, short-term therapies may be considered. For mild to moderate pain, a trial of conservative, nonpharmacologic strategies should be tried first. For those with severe symptoms impacting quality of life, a trial of pharmacologic therapy can be considered after appropriate counseling for medication-related adverse effects. Herein, we have provided a concise summary of a generalized approach to classification, assessment, and management of breast pain.

Implementation of a New Guideline and Educational Sessions to Reduce Low-Value Continuous Pulse Oximetry Among Hospitalized Patients.

OBJECTIVES: The use of continuous pulse oximetry (CPOX) is ubiquitous among hospitalized patients, despite limited evidence that it improves clinical outcomes. The objective of this study was to reduce the use of CPOX among hospitalized patients in the nonintensive care unit and nonprogressive care unit settings. METHODS: This interventional trial included the creation a new local guideline for CPOX use and subsequent staff education. CPOX use, patient acuity, hospital length of stay, and code blue events were measured before and after the intervention. RESULTS: Postintervention there was a clinically significant and sustained decrease in CPOX use of 18% over 1 year. There were no significant changes postintervention in hospital length of stay or number of code blue events. CONCLUSIONS: Development of a guideline for CPOX use and staff education successfully led to a decrease in CPOX use, without an increase in hospital length of stay or code blue events.

Treatment of corneal chemical alkali burns with a crosslinked thiolated hyaluronic acid film.

PURPOSE: The study objective was to test the utilization of a crosslinked, thiolated hyaluronic acid (CMHA-S) film for treating corneal chemical burns. METHODS: Burns 5.5mm in diameter were created on 10 anesthetized, male New Zealand white rabbits by placing a 1N NaOH soaked circular filter paper onto the cornea for 30s. Wounds were immediately rinsed with balanced salt solution (BSS). CMHA-S films were placed in the left inferior fornix of five injured and five uninjured animals. Five animals received no treatment. At 0h, 48h, 96h, and on day 14 post chemical burn creation, eyes were evaluated by white light imaging, fluorescein staining, and optical coherence tomography (OCT). Corneal histology was performed using H&E and Masson's Trichrome stains. RESULTS: Image analysis indicated biocompatible CMHA-S treatment resulted in significant decreases in the areas of corneal opacity at 48h, 96h, and on day 14 postoperatively. A significant increase in re-epithelialization was seen 14days post injury. CMHA-S treated corneas showed significantly less edema than untreated burns. No pathological differences were observed in corneal histological samples as a result of CMHA-S treatment. CONCLUSIONS: CMHA-S films facilitate re-epithelialization and decrease the area of corneal opacity in our corneal alkali burn rabbit model.