RESUMEN
Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy.
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Daño por Reperfusión Miocárdica , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Humanos , Animales , Hormonas/metabolismo , Hormonas/uso terapéutico , Cardiotónicos/farmacología , Cardiotónicos/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen. PATIENTS AND METHODS: Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years. RESULTS: The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36-0.79]; IHC-ER+ 0.55 [0.38-0.79]; GEX-ER+ 0.54 [0.37-0.77]; cytosol-PR+ 0.49 [0.34-0.72]; IHC-PR+ 0.58 [0.40-0.85]; GEX-PR+ 0.55 [0.38-0.80]). Results were similar for OS. INTERPRETATION: These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.
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Neoplasias de la Mama , Tamoxifeno , Humanos , Femenino , Tamoxifeno/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , ARN Mensajero/genética , Quimioterapia Adyuvante , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Receptores de Estrógenos/metabolismo , Hormonas/uso terapéutico , Receptores de Progesterona/metabolismo , Resultado del TratamientoRESUMEN
Vasomotor symptoms (VMS) are associated with adverse health consequences and can cause significant morbidity for postmenopausal women. Although hormone therapy remains the gold standard of VMS treatment in menopausal women, some women have contraindications to or may choose not to take hormone therapy. This article provides an up-to-date overview of the current evidence-based nonhormone therapies available for managing VMS. Evidence supporting various treatment options is reviewed, including lifestyle interventions, mind-body therapies, procedures, pharmacologic agents, and emerging therapies, such as neurokinin-receptor antagonists. The efficacy, safety, and clinical use of these treatments are detailed, offering insights for clinicians to make informed decisions in menopausal VMS management.
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Sofocos , Menopausia , Femenino , Humanos , Sofocos/tratamiento farmacológico , Terapia de Reemplazo de Estrógeno/métodos , Estilo de Vida , Hormonas/farmacología , Hormonas/uso terapéuticoRESUMEN
PURPOSE: Results from the TAILORx trial revealed that the use of adjuvant chemotherapy along with endocrine therapy had no survival advantage in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative (HER2-), node-negative (N0) breast cancer (BC) with an intermediate (11-25) 21-gene recurrence score (RS) in the overall population. However, in patients under age 50 years, adjuvant chemotherapy demonstrated a progression-free survival benefit when the RS ranged from 16-25. We studied this cohort with the population-based national database. METHODS: The 2010-2018 National Cancer Database was used to include patients with BC age 18-50 years, N0, M0, RS 16-25, ER+/progesterone receptor±, and HER2-. Patients were divided into two groups on the basis of adjuvant chemotherapy use, and the survival between them was compared. RESULTS: Adjuvant chemotherapy use was noted in 4,808/15,792 (30.45%) patients. Median RS was 18 and 21 in patients without and with adjuvant chemotherapy, respectively. Factors associated with adjuvant chemotherapy use were higher T stage, poor and moderately differentiated tumors, age <40 years, care at an academic center, Caucasian race, patients undergoing mastectomy, regional lymph node surgery, and radiation therapy. Kaplan-Meier survival at 10 years was better with adjuvant chemotherapy (96.2% v 91.6%). Patients without adjuvant chemotherapy had more adverse outcomes (hazard ratio [HR], 1.683 [95% CI, 1.392 to 2.036]; P < .0001). Subgroup analysis showed that the benefit was significant in patients with RS scores 21-25 (HR, 1.953 [95% CI, 1.295 to 2.945]), ductal histology (HR, 1.521 [95% CI, 1.092 to 2.118]), Caucasian race (HR, 1.655 [95% CI, 1.180 to 2.322]), and 41-50 years age group (HR, 1.732 [95% CI, 1.244 to 2.411]). CONCLUSION: Our study showed an overall survival benefit for adjuvant chemotherapy use in patients with ER-positive, N0 premenopausal BC patients, age less than 50 years, with an intermediate RS score, particularly 21-25.
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Neoplasias de la Mama , Humanos , Persona de Mediana Edad , Adolescente , Adulto Joven , Adulto , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Estudios Retrospectivos , Mastectomía , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Pronóstico , Receptores de Estrógenos/metabolismo , Hormonas/uso terapéutico , Quimioterapia Adyuvante/métodosRESUMEN
Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. Design, Setting, and Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. Main Outcome and Measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). Conclusions and Relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.
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Neoplasias de la Mama , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Hormonas/uso terapéutico , Linfocitos Infiltrantes de Tumor , Estudios Prospectivos , Receptor ErbB-2 , AncianoRESUMEN
INTRODUCTION: Evaluating the benefits and risks of prolonged hormonal treatment with aromatase inhibitors (AIs) for treating hormone-dependent breast cancer. METHODS: A systematic review and meta-analysis was conducted. Studies reporting on randomized clinical trials concerning prolongating hormonal therapy with AIs as compared to a placebo or no prolongation, after an initial five years of hormonal therapy, were eligible. RESULTS: Seven clinical trials were included. Prolonged AI therapy was associated with a statistically significant improvement in disease-free survival (RR=0.70, 95% CI 0.60 to 0.80). A statistically significant increase was observed for osteoporosis (RR=1.17, 95% CI 1.03 to 1.33), hot flushes/flashes (RR=1.27, 95% CI 1.08 to 1.49), myalgia (RR=1.23, 95% CI 1.09 to 1.39), fractures (RR=1.26, 95% CI 1.09 to 1.45) and arthralgia (RR=1.17, 95% CI 1.10 to 1.25). However, no statistically significant association was observed between prolonged AI therapy and overall survival, cardiovascular events, and bone pain. DISCUSSION: Prolonged AI therapy has significant benefits in terms of disease-free survival in women with hormone-dependent breast cancer. However, adverse effects and a lack of evidence for a benefit on overall survival must be considered in the decision-making process regarding adjuvant hormone therapy extension.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de la Aromatasa/efectos adversos , Terapia Combinada , Quimioterapia Adyuvante/efectos adversos , Adyuvantes Inmunológicos/uso terapéutico , Hormonas/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Tamoxifeno/efectos adversosRESUMEN
The causes of vasomotor symptoms, including hot flashes, are not fully understood, may be related to molecular factors, and have a polygenic architecture. Nutrients and bioactive molecules supplied to the body with food are metabolized using various enzymatic pathways. They can induce molecular cell signaling pathways and, consequently, activate effector proteins that modulate processes related to hot flashes in menopausal women. In this review, we analyzed the literature data from the last 5 years, especially regarding genome-wide association study (GWAS) analysis, and selected molecular factors and cell signaling pathways that may potentially be related to hot flashes in women. These are the kisspeptin-GnRH pathway, adipocyte-derived hormones, aryl hydrocarbon receptor signaling, catechol estrogens and estrogen sulfotransferase, inflammatory and oxidative stress biomarkers, and glucose availability. Then, single compounds or groups of food ingredients were selected that, according to experimental data, influence the course of the discussed molecular pathways and thus can be considered as potential natural therapeutic agents to effectively reduce the troublesome symptoms of menopause in women.
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Estudio de Asociación del Genoma Completo , Sofocos , Femenino , Humanos , Sofocos/tratamiento farmacológico , Menopausia/fisiología , Hormonas/uso terapéutico , NutrientesRESUMEN
Breast cancer (BC) is currently one of the most common cancers in women worldwide with a rising tendency. Epigenetics, generally inherited variations in gene expression that occur independently of changes in DNA sequence, and their disruption could be one of the main causes of BC due to inflammatory processes often associated with different lifestyle habits. In particular, hormone therapies are often indicated for hormone-positive BC, which accounts for more than 50-80% of all BC subtypes. Although the cure rate in the early stage is more than 70%, serious negative side effects such as secondary osteoporosis (OP) due to induced estrogen deficiency and chemotherapy are increasingly reported. Approaches to the management of secondary OP in BC patients comprise adjunctive therapy with bisphosphonates, non-steroidal anti-inflammatory drugs (NSAIDs), and cortisone, which partially reduce bone resorption and musculoskeletal pain but which are not capable of stimulating the necessary intrinsic bone regeneration. Therefore, there is a great therapeutic need for novel multitarget treatment strategies for BC which hold back the risk of secondary OP. In this review, resveratrol, a multitargeting polyphenol that has been discussed as a phytoestrogen with anti-inflammatory and anti-tumor effects at the epigenetic level, is presented as a potential adjunct to both support BC therapy and prevent osteoporotic risks by positively promoting intrinsic regeneration. In this context, resveratrol is also known for its unique role as an epigenetic modifier in the regulation of essential signaling processes-both due to its catabolic effect on BC and its anabolic effect on bone tissue.
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Neoplasias de la Mama , Osteoporosis , Femenino , Humanos , Resveratrol/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Osteoporosis/prevención & control , Antiinflamatorios no Esteroideos/uso terapéutico , Hormonas/uso terapéuticoRESUMEN
BACKGROUND: For a tumour profiling test to be of value, it needs to demonstrate that it is changing clinical decisions, improving clinical confidence, and of economic benefit. This trial evaluated the use of the Oncotype DX Breast Recurrence Score® assay against these criteria in 680 women with hormone receptor-positive (HR+), HER2-negative early breast cancer with 1-3 lymph nodes positive (LN+) in the UK National Health Service (NHS). METHODS: Prior to receipt of the Recurrence Score (RS) result, both the physician and the patient were asked to state their preference for or against chemotherapy and their level of confidence on a scale of 1-5. Following receipt of the RS result, the physician and patient were asked to make a final decision regarding chemotherapy and record their post-test level of confidence. RESULTS: Receipt of the RS result led to a 51.5% (95% CI, 47.2-55.8%) reduction in chemotherapy, significantly increased the relative and absolute confidence for both physicians and patients and led to an estimated saving to the NHS of £787 per patient. CONCLUSION: The use of the Oncotype DX assay fulfils the criteria of changing clinical decisions, improving confidence and saving money.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Análisis Costo-Beneficio , Estudios Prospectivos , Medicina Estatal , Reino Unido , Hormonas/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Quimioterapia Adyuvante , Perfilación de la Expresión GénicaRESUMEN
PURPOSE OF REVIEW: The evolving role of stereotactic ablative radiation therapy (SABR) as metastasis-directed therapy (MDT) for oligometastatic prostate cancer (omPCa) will be discussed. RECENT FINDINGS: Oligometastatic disease (OMD) is an intermediate state between localized and wide-spread malignant disease. OMD has recently been spotlighted given the increasing demonstration of clinical benefit from local therapies despite presence of metastatic disease and allure of the curative potential of MDT in select cases. Among the different forms of MDT, SABR has rapidly become a widely adopted treatment modality. Significant efforts in this space have focused on omPCa, owing to its relatively indolent biology, presence of a sensitive and specific serum biomarker and recent advances in molecular imaging. While most studies have evaluated the role of SABR MDT in hormone sensitive omPCa, new emerging clinical data also suggests benefits of SABR MDT for even castration-resistant disease. SUMMARY: Treating omPCa with SABR MDT appears to generate an efficacy signal with minimal morbidity across both hormone-sensitive and castration-resistant disease. However, additional definitive omPCa trial data are needed. Future research efforts should investigate biomarkers for this heterogeneous disease space and the role of SABR MDT in combination with systemic agents to improve upon standard of care treatments.
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Neoplasias de la Próstata , Radiocirugia , Masculino , Humanos , Neoplasias de la Próstata/patología , Radiocirugia/métodos , Hormonas/uso terapéuticoRESUMEN
INTRODUCTION: Current implementation efforts have failed to achieve equitable HIV pre-exposure prophylaxis (PrEP) provision for transgender and gender-diverse (trans) populations. We conducted a choice-based conjoint analysis to measure preferences for key attributes of hypothetical PrEP delivery programmes among a diverse online sample predominantly comprised of transmasculine and nonbinary individuals in the United States. METHODS: Between April 2022 and June 2022, a national online survey with an embedded conjoint analysis experiment was conducted among 304 trans individuals aged ≥18 years in the United States to assess five PrEP programme attributes: out-of-pocket cost; dispensing venue; frequency of visits for PrEP-related care; travel time to PrEP provider; and ability to bundle PrEP-related care with gender-affirming hormone therapy services. Participants responded to five questions, each of which presented two PrEP programme scenarios and one opt-out option per question and selected their preferred programme in each question. We used hierarchical Bayes estimation and multinomial logistic regression to measure part-worth utility scores for the total sample and by respondents' PrEP status. RESULTS: The median age was 24 years (range 18-56); 75% were assigned female sex at birth; 54% identified as transmasculine; 32% as nonbinary; 14% as transfeminine. Out-of-pocket cost had the highest attribute importance score (44.3%), followed by the ability to bundle with gender-affirming hormone therapy services (18.7%). Minimal cost-sharing ($0 out-of-pocket cost) most positively influenced the attribute importance of cost (average conjoint part-worth utility coefficient of 2.5 [95% CI 2.4-2.6]). PrEP-experienced respondents preferred PrEP delivery in primary care settings (relative utility score 4.7); however, PrEP-naïve respondents preferred pharmacies (relative utility score 5.1). CONCLUSIONS: Participants preferred programmes that offered PrEP services without cost-sharing and bundled with gender-affirming hormone therapy services. Bolstering federal regulations to cover PrEP services and prioritizing programmes to expand low-barrier PrEP provision are critical to achieving equitable PrEP provision. Community-engaged implementation research conducted by and in close collaboration with trans community stakeholders and researchers are needed to streamline the design of patient-centred PrEP programmes and develop implementation strategies that are salient to the diverse sexual health needs of trans patients.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Personas Transgénero , Masculino , Adulto , Recién Nacido , Humanos , Femenino , Estados Unidos , Adolescente , Adulto Joven , Persona de Mediana Edad , Homosexualidad Masculina , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Teorema de Bayes , Hormonas/uso terapéutico , Fármacos Anti-VIH/uso terapéuticoRESUMEN
OPINION STATEMENT: Treatment for metastatic hormone-sensitive prostate cancer has undergone significant evolution in recent years, leading to substantial improvements in overall survival. Men are living longer than ever before with a median survival now which is almost 6 years. The timing and extent of metastatic disease combined with individual patient factors helps treatment recommendation of doublet therapy including androgen deprivation (ADT) plus either chemotherapy or androgen receptor signaling inhibition (ARSI) or triplet therapy with ADT+ARSI+chemotherapy. New treatments must continue to be developed to enhance survival with goals of cure. Better biomarkers that allow for more effective treatments will enhance disease control, quality of life, and survival.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/terapia , Antagonistas de Andrógenos/uso terapéutico , Calidad de Vida , Resultado del Tratamiento , Hormonas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Certain transgender women who seek gender-affirming hormone treatment (GAHT) face economic and social barriers that limit or prevent access to medically supervised GAHT. Transgender women facing such barriers might acquire GAHT without prescription, potentially without proper dosage, administration, and health monitoring in the absence of medical supervision. For this report, survey data were analyzed from 1,165 transgender women in seven urban areas in the United States to examine associations between self-reported use of nonprescription GAHT and known correlates of nonprescription GAHT, including cost, insurance coverage for GAHT, homelessness, receiving money or drugs in exchange for sex during the past 12 months (exchange sex), lack of comfort discussing gender with provider, and lack of health care use. After controlling for complex sampling design, transgender women who reported recent health care use or insurance coverage for GAHT were less likely to report nonprescription GAHT, and those reporting recent exchange sex or recent homelessness were more likely to report nonprescription GAHT. Findings suggest that transgender women were more likely to use GAHT without a prescription in situations of economic and social marginalization (e.g., disengagement from health care, lack of insurance or trans-specific health care, homelessness, or engagement in sex work). Public health professionals can use these results to design effective interventions to facilitate prescribed hormone use among transgender women in the United States, although access to housing, trans-affirming health care, and insurance coverage might be needed to prevent nonprescription use.
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Hormonas , Medicamentos sin Prescripción , Personas Transgénero , Femenino , Humanos , Infecciones por VIH , Hormonas/uso terapéutico , Cobertura del Seguro , Autoinforme , Estados Unidos , Medicamentos sin Prescripción/uso terapéuticoRESUMEN
The involvement of interferons (IFNs) in various diseases, including breast cancer, has sparked controversy due to their diverse roles in immunity and significant impact on pathological mechanisms. In the context of breast cancer, the heightened expression of endogenous IFNs has been linked to anti-tumor activity and a favorable prognosis for patients. Within the tumor tissue and microenvironment, IFNs initiate a cascade of molecular events involving numerous factors, which can lead to either cooperative or repressive interactions. The specific functions of IFNs in breast cancer vary depending on the two major disease phenotypes: hormone dependent (or responsive) and hormone independent (or unresponsive) breast cancer. Hormone dependence is determined by the presence of estrogen receptors (ERs). The interplay between the IFN and ER signaling pathways, and the involvement of intermediate factors such as NFκB, are areas that have been somewhat under-researched, but that hold potential importance for the understanding and treatment of breast cancer. This review aims to provide a comprehensive overview of the actions of IFNs in breast cancer, particularly in relation to the different breast cancer phenotypes and the significance of comprehending the underlying mechanisms. Furthermore, the use of IFN-based therapies in cancer treatment remains a topic of debate and has not yet gained widespread acceptance. However, emerging discoveries may redirect focus towards the potential of IFN-based therapies.
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Neoplasias de la Mama , Interferones , Humanos , Femenino , Interferones/uso terapéutico , Interferones/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Transducción de Señal , Hormonas/uso terapéutico , Microambiente TumoralRESUMEN
PURPOSE: Despite major increases in the longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC), most men still die of prostate cancer. Phase III trials assessing new therapies in mHSPC with overall survival (OS) as the primary end point will take approximately a decade to complete. We investigated whether radiographic progression-free survival (rPFS) and clinical PFS (cPFS) are valid surrogates for OS in men with mHSPC and could potentially be used to expedite future phase III clinical trials. METHODS: We obtained individual patient data (IPD) from 9 eligible randomized trials comparing treatment regimens (different androgen deprivation therapy [ADT] strategies or ADT plus docetaxel in the control or research arms) in mHSPC. rPFS was defined as the time from random assignment to radiographic progression or death from any cause whichever occurred first; cPFS was defined as the time from random assignment to the date of radiographic progression, symptoms, initiation of new treatment, or death, whichever occurred first. We implemented a two-stage meta-analytic validation model where conditions of patient-level and trial-level surrogacy had to be met. We then computed the surrogate threshold effect (STE). RESULTS: IPD from 6,390 patients randomly assigned from 1994 to 2012 from 13 units were pooled for a stratified analysis. The median OS, rPFS, and cPFS were 4.3 (95% CI, 4.2 to 4.5), 2.4 (95% CI, 2.3 to 2.5), and 2.3 years (95% CI, 2.2 to 2.4), respectively. The STEs were 0.80 and 0.81 for rPFS and cPFS end points, respectively. CONCLUSION: Both rPFS and cPFS appear to be promising surrogate end points for OS. The STE of 0.80 or higher makes it viable for either rPFS or cPFS to be used as the primary end point that is surrogate for OS in phase III mHSPC trials with testosterone suppression alone as the backbone therapy and would expedite trial conduct.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológico , Supervivencia sin Progresión , Antagonistas de Andrógenos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hormonas/uso terapéutico , Supervivencia sin EnfermedadRESUMEN
Hyperphosphatemia is a common feature in patients with impaired kidney function and is associated with increased risk of cardiovascular disease. This phenomenon extends to the general population, whereby elevations of serum phosphate within the normal range increase risk; however, the mechanism by which this occurs is multifaceted, and many aspects are poorly understood. Less than 1% of total body phosphate is found in the circulation and extracellular space, and its regulation involves multiple organ cross talk and hormones to coordinate absorption from the small intestine and excretion by the kidneys. For phosphate to be regulated, it must be sensed. While mostly enigmatic, various phosphate sensors have been elucidated in recent years. Phosphate in the circulation can be buffered, either through regulated exchange between extracellular and cellular spaces or through chelation by circulating proteins (ie, fetuin-A) to form calciprotein particles, which in themselves serve a function for bulk mineral transport and signaling. Either through direct signaling or through mediators like hormones, calciprotein particles, or calcifying extracellular vesicles, phosphate can induce various cardiovascular disease pathologies: most notably, ectopic cardiovascular calcification but also left ventricular hypertrophy, as well as bone and kidney diseases, which then propagate phosphate dysregulation further. Therapies targeting phosphate have mostly focused on intestinal binding, of which appreciation and understanding of paracellular transport has greatly advanced the field. However, pharmacotherapies that target cardiovascular consequences of phosphate directly, such as vascular calcification, are still an area of great unmet medical need.
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Enfermedades Cardiovasculares , Hiperfosfatemia , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Fosfatos/metabolismo , Enfermedades Cardiovasculares/metabolismo , Hiperfosfatemia/tratamiento farmacológico , Calcificación Vascular/etiología , Hormonas/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVE: Androgen-deprivation therapy is the mainstay of treatment for patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). However, the intensification of treatment with either docetaxel or novel anti-androgens (abiraterone-acetate plus prednisone [AAP], enzalutamide, and apalutamide) is being recommended based on the improved clinical outcomes and quality of life among patients. This study aimed to determine the most cost-effective drug for treatment intensification for patients with mHSPC in India. METHODS: A Markov model was developed with four health states: progression-free survival, progressive disease, best supportive care, and death. Lifetime costs and consequences were estimated for four treatment sequences: AAP-first, enzalutamide-first, apalutamide-first, and docetaxel-first. Incremental cost per quality-adjusted life-year (QALY) gained with a given treatment option was compared against the next best alternative and assessed for cost effectiveness using a willingness to pay threshold of 1 × per capita gross domestic product in India. RESULTS: We estimated that the total lifetime cost per patient was â¹1,367,454 (US$17,487), â¹2,168,885 (US$27,735), â¹7,678,501 (US$98,190), and â¹1,358,746 (US$17,375) in the AAP-first, enzalutamide-first, apalutamide-first, and docetaxel-first treatment sequence, respectively. The mean quality-adjusted life-years lived per patient were 4.78, 5.03, 3.22, and 2.61, respectively. The AAP-first sequence incurs an incremental cost of â¹4014 (US$51) per quality-adjusted life-year gained as compared with the docetaxel-first sequence, with a 87% probability of being cost effective at the willingness-to-pay threshold of 1 × per-capita gross domestic product of India. The use of AAP-first also incurs an incremental net monetary benefit of â¹396,491 (US$5070) as compared with the docetaxel-first treatment sequence. Nearly a 48% reduction in the price of enzalutamide is required to make it a cost-effective treatment sequence as compared with AAP-first in India. CONCLUSIONS: We concur with the inclusion of standard-dose AAP in India's publicly financed health insurance scheme for the intensification of treatment in mHSPC as it is the only cost-effective sequence among the various novel anti-androgens when compared with the docetaxel-first treatment sequence. Furthermore, a systematic reduction in the price of enzalutamide would further help to improve clinical outcomes among patients with mHSPC.
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Benzamidas , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Docetaxel/uso terapéutico , Análisis de Costo-Efectividad , Antagonistas de Andrógenos/uso terapéutico , Calidad de Vida , Análisis Costo-Beneficio , Prednisona/uso terapéutico , Hormonas/uso terapéuticoRESUMEN
Breast cancer increases the risk of type 2 diabetes 1.07- to 4.27-fold, depending on patient and treatment characteristics, such as postmenopausal status, hormone therapy, and treatment with adjuvant chemotherapy. We evaluated the current evidence and considered the role of increased screening for type 2 diabetes in this at-risk population. This narrative review was conducted using Embase and MEDLINE databases. Keywords including diabetes and breast cancer were used. Articles were limited to those published in English between 2000 and 2022. It appears that the increased risk of diabetes begins at or just after breast cancer diagnosis, and remains elevated for at least 10 to 15 years, with greatest risk in the first 2 years after diagnosis. Subsets of patients with breast cancer appear to be at higher risk of developing type 2 diabetes, including those who were treated with adjuvant chemotherapy or hormone therapy. Further investigation is needed to develop specific screening recommendations for this population. If screening is performed with a glycated hemoglobin test during breast cancer treatment, then hemoglobin should be measured at the same time given the association of breast cancer therapy with anemia. Presence of breast cancer should not be a major factor when choosing among available antihyperglycemic agents. Overall, patients with breast cancer appear to be at an increased risk of developing type 2 diabetes. This increased risk suggests the need for further investigation to develop specific screening recommendations for this at-risk population.
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Neoplasias de la Mama , Diabetes Mellitus Tipo 2 , Humanos , Femenino , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Detección Precoz del Cáncer , Factores de Riesgo , Hormonas/uso terapéuticoRESUMEN
BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a systemic disease that is limited to the skin. cPAN usually presents with cutaneous reticular cyanotic, erythematous and palpable nodules, and cutaneous ulcers.Research has indicated that the use of hormones and immunosuppressive drugs can delay ulcer healing and associated neuropathy, and also elevate the risk of disease recurrence upon their reduction or withdrawal. Therefore, it is a necessary to find a safe and effective approach that minimize hormone side effects in ulcer treatment. CASE PRESENTATION: The patient, a 48-year-old female of Han Chinese ethnicity, has suffered from recurrent erythema nodosum on both lower limbs for 8 years. The condition was aggravated by skin breakdown over the last 3 months. Despite multiple treatments, the patient's condition did not improve significantly, leading to the exploration of a combined approach of traditional Chinese and Western medicine. Following six months of combined traditional Chinese and Western medicine treatment, t the patient's newborn erythema and ulcers on both lower limbs did not reappear, and the ulcers gradually decreased in size and the erythema disappeared. The patient took the TCM regularly until April 15, 2023, when the ulcers were completely healed. Three months after the patient stopped taking TCM, the ulcers had completely healed with no recurrence, as observed during the follow-up visit on July 14th, 2023. CONCLUSION: Traditional Chinese Medicine Combined with Low-Dose Hormones May Effectively Treat Bilateral Lower Extremity Skin Ulcers Caused by Cutaneous Polyarteritis Nodosa.
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Poliarteritis Nudosa , Femenino , Recién Nacido , Humanos , Persona de Mediana Edad , Poliarteritis Nudosa/complicaciones , Poliarteritis Nudosa/tratamiento farmacológico , Úlcera , Extremidad Inferior , Eritema , Hormonas/uso terapéuticoRESUMEN
BACKGROUND: Transgender and gender-diverse (TGD) people have a high prevalence of psychotropic medication use, yet knowledge about the patient-level psychotropic medication burden is limited. TGD patients may take hormone therapy to meet their gender expression goals. Potential drug-hormone interactions exist between psychotropic medications and hormone therapy, requiring increased knowledge about psychotropic medication use for TGD adults undergoing hormone therapy. OBJECTIVES: The objective of this study was to examine the extent of psychotropic medication polypharmacy in a cohort of TGD adults within 2 years of starting hormone therapy. We also characterized potential drug-hormone interactions and the association with psychotropic polypharmacy. METHODS: Retrospective cross-sectional analysis of patients with ≥1 transgender health-related visit (2007-2017) in the University of Washington Medical System (Seattle, WA). Eligible patients had ≥1 psychotropic medication including antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics ordered within 2 years of starting hormone therapy (testosterone or estradiol with or without spironolactone, progesterone, finasteride, or dutasteride). We defined psychotropic polypharmacy as ≥2 psychotropic medication orders with overlapping treatment durations for at least 90 days and characterized potential drug-hormone interactions (Lexicomp, Hudson, OH). We descriptively summarized patients with and without polypharmacy (frequencies and percentages) and compared drug-hormone interactions using chi-square or Fishers exact tests (P < 0.05 considered significant). RESULTS: A total of 184 patients had ≥1 psychotropic medication order within 2 years of hormone therapy; 68 patients (37.0%) had psychotropic polypharmacy. The most frequent type of psychotropic polypharmacy was antidepressant+sedative-hypnotic (18 of 68, 26.5%). More patients had a potential drug-hormone interaction among those with psychotropic polypharmacy (23 of 68, 33.8%) versus those without (8 of 116, 6.9%, P < 0.001). CONCLUSION: Among TGD patients on psychotropic medications within 2 years of hormone therapy, one-third had psychotropic polypharmacy. Most polypharmacy types appeared to align with mental health treatment guidelines. The number of patients with a potential drug-hormone interaction was significantly higher among those with polypharmacy. Prospective studies are needed to characterize drug-hormone interactions.