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.

Following the High-Risk Patient: Breast Cancer Risk-Based Screening.

Breast cancer (BC) is the most common cancer occurring in women in the USA today, and accounts for more than 40,000 deaths annually (Giaquinto in CA Cancer J Clin 72: 524-541, 2022). While breast cancer survival has improved over the past decades, incidence has increased, and diagnoses are being made at younger ages. This emphasizes the importance of risk evaluation, accurate prediction, and effective mitigation and risk reduction strategies. Enhanced screening can help detect cancers at an earlier stage, thus improving morbidity and mortality. This review addresses the recognition of women at high-risk for BC and monitoring strategies for those at high risk.

Atypical hyperplasia of the breast: Clinical cases and management strategies.

Atypical hyperplasia of the breast is a histopathologic lesion identified incidentally on image-guided breast biopsy. It is associated with a substantial increase in lifetime risk for breast cancer. Clinicians should counsel women with atypical hyperplasia regarding risk-reducing strategies, which include preventive endocrine therapy options, enhanced surveillance imaging, and lifestyle modifications. In this review, we describe 5 different but common clinical case scenarios for atypical hyperplasia of the breast and review management strategies for each scenario.

Breast cancer risk evaluation for the primary care physician.

Primary care physicians are typically the frontline clinicians who assess female patients for their risk of breast cancer, doing so by using a combination of risk algorithms and collecting personal and family medical histories. Patients found to be at increased risk of breast cancer, defined as > 20% overall lifetime risk, are candidates for enhanced screening. This review notes risk factors, determinants of risk, and a systematic approach for primary care physicians to assess and manage patients at risk of breast cancer.

Impact of Nasopharyngeal FilmArray Respiratory Panel Results on Antimicrobial Decisions in Hospitalized Patients.

Objective: To determine whether results of the nasopharyngeal FilmArray respiratory panel (NP-FARP) influenced antibiotic decisions. Methods: We reviewed the medical records of nonintensive care unit (ICU) inpatients that had an NP-FARP performed at our institution between June 2013 and June 2014. The inpatient records were reviewed 48 hours after the NP-FARP for the following data: demographic information; NP-FARP, serum procalcitonin, and methicillin-resistant Staphylococcus aureus nasal swab (MRSA NS) results; antibiotics prior and post-48 hours of the NP-FARP result; and the current immunosuppression status. Clinical outcome data were not obtained. Patients were categorized into those who had a positive (+) or a negative (-) NP-FARP. We further subdivided these two categories into groups A, B, and C based on the antibiotic modifications 48 hours after their NP-FARP result. Group A included patients who were never initiated on antimicrobial therapy. Patients whose antibiotics were discontinued or deescalated were placed in group B. Patients with antibiotic escalation or continuation without change constituted group C. We compared and analyzed groups A, B, and C in the (+) and (-) NP-FARP cohorts. Results: A total of 545 patients were included. There were 143 (26%) patients with positive and 402 (74%) patients with negative NP-FARPs. Comparison of groups A, B, and C between those with a (+) and (-) NP-FARP were as follows: (+) A and (-) A, 28/143 (20%) and 84/402 (21%); (+) B and (-) B, 59/143 (41%) and 147/402 (37%); and (+) C and (-) C, 56/143 (39%) and 171/402 (43%), respectively. We found no statistically significant differences between groups (+) A versus (-) A, (+) B versus (-) B, and (+) C versus (-) C with respect to age, gender, MRSA NS result, procalcitonin result, or concurrent immunosuppression. Conclusion: In non-ICU inpatients, NP-FARP alone or in combination with procalcitonin or MRSA NS did not influence antibiotic decisions during the study period.

Microbiologic yield of bronchoalveolar lavage specimens from stem cell transplant recipients.

PURPOSE: Stem cell transplant (SCT) recipients commonly undergo bronchoalveolar lavage (BAL) collection as an infectious pulmonary work-up. Previous studies report the utility and overall diagnostic yield of fiberoptic bronchoscopy with BAL in this vulnerable population, though none focused purely on microbiologic yield or made comparisons with less invasive means of pathogen detection. We sought to determine and elaborate on the microbiologic yield of BAL in SCT recipients, assess a correlation between BAL studies and less invasive means of pathogen detection, and assess the utility of repeating a BAL within 30 days. METHODS: Between January 1, 2009, and July 31, 2013, we reviewed medical records of 125 SCT recipients who underwent 179 BALs. In addition to demographic information and details pertaining to their SCT, a comprehensive review of their microbiologic data was performed and recorded. RESULTS: Our study showed an overall BAL microbiologic yield of 40%, despite 92% of patients receiving broad-spectrum antimicrobial therapy at the time of the BAL procedure. CONCLUSIONS: Although an initial BAL sample in this population provides crucial microbiologic information, repeating the procedure within 30 days may have minimal additional microbiologic yield. BAL continues to be an essential diagnostic tool in SCT recipients undergoing an infectious pulmonary work-up.

Introducing routine HIV screening for patients on an internal medicine residency inpatient service: a quality improvement project.

The US Centers for Disease Control and Prevention (CDC) recommend human immunodeficiency virus (HIV) screening for all persons aged 13 to 64 years who present to a health care provider. We sought to improve adherence to the CDC guidelines on the Internal Medicine Resident Hospital Service. We surveyed residents about the CDC guidelines, sent email reminders, provided education, and engaged them in friendly competition. Credit for guideline adherence was awarded if an offer of HIV screening was documented at admission, if a screening test was performed, or if a notation in the resident sign out sheet indicated why screening was not performed. We examined HIV screening of a postintervention group of patients admitted between August 8, 2012, and June 30, 2013, and compared them to a preintervention group admitted between August 1, 2011, and June 30, 2012. Postintervention offers of HIV screening increased significantly (7.9% [44/559] vs 55.5% [300/541]; P<.001), as did documentation of residents' contemplation of screening (8.9% [50/559] vs 67.5% [365/541]; P<.001). A significantly higher proportion of HIV screening tests was ordered postintervention (7.7% [43/559] vs 44.4% [240/541]; P<.001). Monthly HIV screening documentation ranged from 0% (0/53) to 17% (9/53) preintervention, whereas it ranged from 30.6% (11/36) to 100% (62/62) postintervention. HIV screening adherence can be improved through resident education, friendly competition, and system reminders. Barriers to achieving sustained adherence to the CDC guidelines include a heterogeneous patient population and provider discomfort with the subject.

Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer.

We used DNA content flow cytometry followed by oligonucleotide array based comparative genomic hybridization to survey the genomes of 326 tumors, including 41 untreated surgically resected triple negative breast cancers (TNBC). A high level (log2ratio ≥ 1) 9p24 amplicon was found in TNBC (12/41), glioblastomas (2/44), and colon carcinomas (2/68). The shortest region of overlap for the amplicon targets 9p24.1 and includes the loci for PD-L1, PD-L2, and JAK2 (PDJ amplicon). In contrast this amplicon was absent in ER+ (0/8) and HER2+ (0/15) breast tumors, and in pancreatic ductal adenocarcinomas (0/150). The PDJ amplicon in TNBCs was correlated with clinical outcomes in group comparisons by two-sample t-tests for continuous variables and chi-squared tests for categorical variables. TNBC patients with the PDJ amplicon had a worse outcome with worse disease-free and overall survival. Quantitative RT-PCR confirmed that the PDJ amplicon in TNBC is associated with elevated expression of JAK2 and of the PD-1 ligands. These initial findings demonstrate that the PDJ amplicon is enriched in TNBC, targets signaling pathways that activate the PD-1 mediated immune checkpoint, and identifies patients with a poor prognosis.

Stem cell transplantation demonstrates that Sox6 represses epsilon y globin expression in definitive erythropoiesis of adult mice.

Sox6, a member of the Sox transcription factor family, is essential for the silencing of epsilon y globin gene expression in definitive erythropoiesis of mice. Homozygous Sox6-null mice are neonatally lethal, precluding analysis at later stages. We created adult mice that are deficient in Sox6 specifically in hematopoietic tissues by transplanting embryonic liver stem cells from Sox6-deficient mice into lethally irradiated congenic wild-type adult mice. The mice receiving mutant stem cells (mutant engrafted) showed high expression levels of epsilon y in bone marrow, spleen, and circulating blood compared with mice receiving wild-type and heterozygous stem cells (control engrafted). The level of expression of epsilon y in circulating blood was directly correlated with the percentage of successful mutant donor cell engraftment. Additionally, the mutant engrafted adult mice showed an increase in erythroid precursor cells in bone marrow, spleen, and blood. Thus, Sox6 continues to function as a major regulator of epsilon y in adult definitive erythropoiesis and is required for normal erythrocyte maturation. Therefore, Sox6 may provide a novel therapeutic target by reactivating epsilon y in patients with hemoglobinopathies such as sickle cell anemia and beta-thalassemia.