Hormone Therapy Research Articles

Uveal effusion syndrome following hormonal therapy for prostate cancer: a rare ophthalmic manifestation

Uveal effusion syndrome following hormonal therapy for prostate cancer: a rare ophthalmic manifestation

Treatment utilization and non-drug interventions for vasomotor symptoms in breast cancer survivors taking endocrine therapy: Real-world findings from the United States and Europe

ObjectivesVasomotor symptoms induced by endocrine therapy are common in breast cancer survivors and a risk factor for therapy discontinuation and lower quality of life. The REALISE study evaluated the real-world treatment landscape in breast cancer survivors with vasomotor symptoms taking endocrine therapy, including pharmaceuticals, lifestyle changes, and over-the-counter products. Study designSecondary analysis of the Adelphi Vasomotor Disease Specific Programme™, a large cross-sectional point-in-time survey and chart review conducted in the US and five European countries (February–October 2020). Oncologists provided demographic, clinical, and treatment data for adult breast cancer survivors with induced vasomotor symptoms taking endocrine therapy (tamoxifen or aromatase inhibitors); patients voluntarily completed self-report surveys on their symptom severity, concomitant sleep and/or mood symptoms, lifestyle changes, and use of over-the-counter products. Main outcome measuresPatient characteristics; vasomotor symptom severity; use of pharmaceuticals, lifestyle changes, and over-the-counter products (from pre-defined lists); lines of treatment. ResultsOverall, 77 oncologists reported data for 618 breast cancer survivors, of whom 183 (29.6 %) completed self-report forms. Physicians classified 420 (68.0 %) women as experiencing moderate-severe vasomotor symptoms, of whom 66.9 % were receiving treatment. In total, 15.2 % of all breast cancer survivors were prescribed systemic hormone therapy. Venlafaxine (24.7 %), citalopram (16.5 %), and paroxetine (13.6 %) were the most commonly prescribed nonhormonal medications. Lifestyle changes (77.8 %) and over-the-counter products (61.6 %) were common, especially in patients with concomitant sleep and/or mood symptoms. ConclusionsDespite contraindications, a relatively large proportion of treatment-seeking breast cancer survivors with vasomotor symptoms were prescribed systemic hormone therapy. This, combined with high patient-reported use of lifestyle changes and over-the-counter products, suggests a need for symptomatic relief and demand for new nonhormonal alternatives with established safety profiles in this population.

Computational model predicts patient outcomes in Luminal B breast cancer treated with endocrine therapy and CDK4/6 inhibition.

Development of a computational biomarker to predict, prior to treatment, the response to CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy in patients with breast cancer. A mechanistic mathematical model that accounts for protein signaling and drug mechanisms of action was developed and trained on extensive, publicly available data from breast cancer cell lines. The model was built to provide a patient-specific response score based on the expression of six genes (CCND1, CCNE1, ESR1, RB1, MYC and CDKN1A). The model was validated in five independent cohorts of 148 patients in total with early-stage or advanced breast cancer treated with endocrine therapy and CDK4/6i. Response was measured either by evaluating Ki67 levels and PAM50 risk of relapse (ROR) after neoadjuvant treatment or by evaluating progression-free survival (PFS). The model showed significant association with patient´s outcomes in all five cohorts. The model predicted high Ki67 (area under the curve; AUC (95% confidence interval) of 0.80 (0.64 - 0.92), 0.81 (0.60 - 1.00) and 0.80 (0.65 - 0.93)) and high PAM50 ROR (AUC of 0.78 (0.64 - 0.89)). This observation was not obtained in patients treated with chemotherapy. In the other cohorts, patient stratification based on the model prediction was significantly associated with PFS (hazard ratio=2.92 (95% CI 1.08 - 7.86), p=0.034 and HR=2.16 (1.02 4.55), p=0.043). A mathematical modeling approach accurately predicts patient outcome following CDK4/6i plus endocrine therapy, which marks a step towards more personalized treatments in patients with Luminal B breast cancer.

Oral estrogen receptor PROTAC® vepdegestrant (ARV-471) is highly efficacious as monotherapy and in combination with CDK4/6 or PI3K/mTOR pathway inhibitors in preclinical ER+ breast cancer models.

Estrogen Receptor (ER) alpha signaling is a known driver of ER-positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Combining endocrine therapy (ET) such as fulvestrant with CDK4/6, mTOR or PI3K inhibitors is now a central strategy for the treatment of ER+ advanced breast cancer. However, suboptimal ER inhibition and resistance resulting from ESR1 mutation dictates that new therapies are needed. A medicinal chemistry campaign identified vepdegestrant (ARV-471), a selective, orally bioavailable, potent small molecule PROteolysis-TArgeting Chimera (PROTAC®) degrader of ER. We used biochemical and intracellular target engagement assays to demonstrate the mechanism of action of vepdegestrant, and ESR1 wild-type and mutant ER+ preclinical breast cancer models to demonstrate ER degradation-mediated tumor growth inhibition. Vepdegestrant induced ≥90% degradation of wild-type (WT) and mutant ER, inhibited ER-dependent breast cancer cell line proliferation in-vitro and achieved significant tumor growth inhibition (TGI) (87-123%) in MCF7 orthotopic xenograft models, better than the ET agent fulvestrant (31-80% TGI). In the hormone-independent ER Y537S patient derived xenograft (PDX) breast cancer model ST941/HI, vepdegestrant achieved tumor regressions and was similarly efficacious in the ST941/HI/PBR palbociclib-resistant model (102% TGI). Vepdegestrant induced robust tumor regressions in combination with each of the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib, the mTOR inhibitor everolimus, and the PI3K inhibitors alpelisib and inavolisib. Vepdegestrant achieved greater ER degradation in-vivo compared to fulvestrant, which correlated with improved tumor growth inhibition, suggesting vepdegestrant could be a more effective backbone ET for patients with ER+/HER2- breast cancer.

Management and outcomes of breast cancer patients with radiotherapy interruption.

Many cancer patients have not received timely treatment or even had treatment interruptions due to the COVID-19 pandemic. The objective of this investigation was to evaluate whether the prognosis of patients with breast cancer after surgery was affected by any interruptions in radiotherapy. The healthcare documents for breast cancer patients experiencing radiotherapy interruption after surgery, including treatment-related characteristics, and time of interruption, type of disease progression, and survival status, were collected between January and April 2020 during the Wuhan blockade. The final number of patients included was 148, and neither the Kaplan-Meier (KM) survival curve nor the cross-tabulation analysis found statistical significance. Cox regression analysis also did not identify risk factors associated with PFS. The prognosis of patients with postoperative breast cancer may not be significantly impacted by the interruption of radiotherapy, given its integration with additional treatments like targeted and endocrine therapies.

Reliability of dynamic and isometric upper muscle strength testing in breast cancer survivors.

Breast cancer is the most common cancer in women worldwide, and its treatment usually involves a combination of many medical procedures, including surgery, chemotherapy, radiotherapy, and hormonal therapy. One of the detrimental effects on physical function is reduced upper limb muscle strength. This study aimed to evaluate upper body strength intra-day and inter-day (test-retest) reliability using the handgrip strength test (HGS) and the bilateral isometric bench press (BIBP) and the test-retest reliability of the one repetition maximum on the bench press (BP-1RM) in breast cancer survivors (BCS). Thirty-two (52.94 ± 8.99 yrs) BCS participated in this study. The muscle strength tests were performed in two different moments, three to seven days apart. Intraclass coefficient correlation (ICC) and coefficient of variation (CV) were used to assess the reliability. Standard error of measurement (SEM), typical error of measurement (TEM), and minimally detectable change (MDC) analyses were performed. The Bland-Altman analysis was used to assess the agreement between test-retest. We found a reliability that can be described as "high" to "very high" (ICC ≥ 0.88; CV ≤ 10%) for intra-day and test-retest. SEM% and MDC% were lower than 5% and 11%, respectively, for all intra-day testing. SEM% and TEM% ranged from 3% to 11%, and MDC% ranged from 9% to 23% in the test-retest reliability. The agreement demonstrated a systematic bias ranging from 2.3% to 6.0% for all testing, and a lower systematic bias may be presented in the non-treated side assessed by HGS and BIBP. HGS, BIBP, and BP-1RM assessments are reliable for measuring upper-body muscle strength in BCS.

Lutetium-specific prostatic membrane antigen (luPSMA) treatment for metastatic castration- resistant prostate cancer

Introduction: Cancer is one of the leading causes of death globally, with the majority of cases occurring in low-income countries. There are more than a hundred types, divided into sarcomas and carcinomas. Prostate cancer is the most common cancer among men and is usually asymptomatic. Treatment depends on the stage of the disease and may include surgery, hormone therapy, and radiation therapy. In advanced stages, new treatments such as the radiopharmaceutical LuPSMA are investigated to improve patients' quality of life. Objective: To analyze the efficacy of treatment with the radiopharmaceutical LuPSMA in patients diagnosed with metastatic prostate cancer through a literature review. Methodology: An exploratory-descriptive literature review with a qualitative approach was conducted, based on books and scientific articles. Data collection took place between 2019 and 2024, including complete and relevant documents on the topic, without language restriction, and excluding irrelevant, duplicate, or incomplete materials. The databases used were LILACS, SciELO, and PubMed, using the descriptors "Prostate Neoplasms," "Lutetium," and "Positron Emission Tomography combined with Computed Tomography" in Portuguese and English, added by the boolean operator "AND". Results: A total of 189 articles were found, of which only 30 were selected, after reading the titles and abstracts, according to the inclusion criteria, showing that theranostics with LuPSMA presents significant results in the quality and survival of patients with mCRPC. Conclusion: The results showed that LuPSMA significantly increased overall survival and progression-free survival compared to standard treatment, while being well tolerated with manageable adverse effects. However, there are uncertainties about the therapeutic response and prognosis in patients with low PSMA expression, indicating the need for further research. The study has contributed to imaging and oncology, offering new perspectives on alternative therapies for metastatic cancer and serving as a basis for future investigations into imaging-guided radionuclide therapies.

Sheehan’s syndrome presenting with panhypopituitarism and central diabetes insipidus: a case report

BackgroundSheehan’s syndrome is a rare condition, which is classically characterized by anterior pituitary hypofunction following postpartum shock or hemorrhage. While diabetes insipidus (DI) is not commonly associated with Sheehan’s syndrome, we present a rare case of a multiparous female developing rapid-onset panhypopituitarism and DI following severe postpartum hemorrhage.Case presentationA previously healthy 39-year-old woman, gravida 5, para 4, presented with hypovolemic shock after vaginal delivery, attributed to severe postpartum hemorrhage, necessitating emergent hysterectomy. Although her shock episodes resolved during hospitalization, she developed intermittent fever, later diagnosed as adrenal insufficiency. Administration of hydrocortisone effectively resolved the fever. However, she subsequently developed diabetes insipidus. Diagnosis of Sheehan’s syndrome with central diabetes insipidus was confirmed through functional hormonal tests and MRI findings. Treatment consisted of hormone replacement therapy, with persistent panhypopituitarism noted during a ten-year follow-up period.ConclusionsSheehan’s syndrome is a rare complication of postpartum hemorrhage. Central diabetes insipidus should be suspected, although not commonly, while the patient presented polyuria and polydipsia. Besides, the potential necessity for long-term hormonal replacement therapy should be considered.

The Anticancer Effects and Therapeutic Potential of Kaempferol in Triple-Negative Breast Cancer

Breast cancer is the second-leading cause of cancer death among women in the United States. Triple-negative breast cancer (TNBC), a subtype of breast cancer, is an aggressive phenotype that lacks estrogen (ER), progesterone (PR), and human epidermal growth (HER-2) receptors, which is challenging to treat with standardized hormonal therapy. Kaempferol is a natural flavonoid with antioxidant, anti-inflammatory, neuroprotective, and anticancer effects. Besides anti-tumorigenic, antiproliferative, and apoptotic effects, kaempferol protects non-cancerous cells. Kaempferol showed anti-breast cancer effects by inducing DNA damage and increasing caspase 3, caspase 9, and pAMT expression, modifying ROS production by Nrf2 modulation, inducing apoptosis by increasing cleaved PARP and Bax and downregulating Bcl-2 expression, inducing cell cycle arrest at the G2/M phase; inhibiting immune evasion by modulating the JAK-STAT3 pathway; and inhibiting the angiogenic and metastatic potential of tumors by downregulating MMP-3 and MMP-9 levels. Kaempferol holds promise for boosting the efficacy of anticancer agents, complementing their effects, or reversing developed chemoresistance. Exploring novel TNBC molecular targets with kaempferol could elucidate its mechanisms and identify strategies to overcome limitations for clinical application. This review summarizes the latest research on kaempferol’s potential as an anti-TNBC agent, highlighting promising but underexplored molecular pathways and delivery challenges that warrant further investigation to achieve successful clinical translation.

Expression of miR-34a, RASSF1A and E-cadherin in relation to PRB in endometrioid carcinoma and its precursor.

The current study aims to evaluate the levels of miR-34a, RASSF1A, and E-cadherin in relation to the levels of isoform B of progesterone receptor (PRB) in endometrioid carcinoma (EC) and atypical hyperplasia (AEH) and their association with clinicopathological parameters. 105 cases (35 EC, 35 AEH, and 35 control) were involved in this study. Cases of AEH received treatment, and other samples were obtained after 6 months to assess the response. E-cadherin and PRB were assessed by immunohistochemistry (IHC), RASSFA methylation by MSP-PCR, and its serum level by ELISA and miR-34a via quantitative PCR. The expressions of miR-34a, RASSF1A, E-cadherin, and PRB differ among the studied groups; all were higher in normal compared with AEH and EC, with a statistically significant difference. The higher PRB expression and decreased miR-34a and RASSF1A expression were associated with resistance to hormonal therapy in AEH. High PRB in EC is associated with lower RASSFA1, E-cadherin, and miR-34a. Decreased expressions of RASSF1A, miR-34a, and E-cadherin had a significant connection to advanced stages. Expression of PRB and miR-34a and serum levels of RASSF1A predict response to treatment in cases of AEH. High PRB and low E-cadherin expression are associated with progressive disease in EC.

Peri-operative care of transgender and gender-diverse individuals: guidance for clinicians and departments.

The objective of this document is to guide best practice to ensure the safety and dignity of transgender and gender-diverse people in the peri-operative period. While transgender and gender-diverse people may have specific health needs in relation to gender dysphoria, their health requirements go beyond their gender identity. Most doctors will provide care to someone who is transgender or gender-diverse at some stage in their career. It is therefore important that all anaesthetists are educated on specific considerations when caring for these patients. A working party was assembled consisting of individuals with experience in direct clinical care of the relevant patient group, those who have expertise in endocrinology and gender-affirming hormones, educators on the topic of transgender and gender-diverse healthcare, and authors of both cisgender and transgender identities. After discussion among the working party, targeted searches of literature were undertaken. The authors initially came up with a list of over 25 recommendations which was subsequently revised to a list of 15 recommendations after further review by the working party. These included airway assessment and management; management of hormonal therapy; relevant issues in obstetric anaesthesia; and hospital infrastructure and processes. This document provides the first guidance produced to advise on best practice to ensure the safety and dignity of trans and gender-diverse individuals in the peri-operative period.

Empowering Health and Identity: The Vital Role of Gender-affirming Care for Individuals With HIV.

Comprehensive healthcare for all includes gender-affirming hormone therapy for transgender and nonbinary individuals. It is the unique privilege of HIV providers, who take care of a disproportionate number of transgender people, to provide gender-affirming hormone therapy along with antiretroviral therapy. It could increase viral suppression rates, increase overall health outcomes, and decrease gender health disparities.

Hormone therapy is associated with lower Alzheimer’s disease tau biomarkers in post-menopausal females -evidence from two independent cohorts

BackgroundFemales represent approximately 70% of the Alzheimer’s disease (AD) cases and the literature has proposed a connection between the decreased estrogen levels during menopause and an increased AD risk. Previous investigations have predominantly focused on assessing how hormone therapy (HT) affects the likelihood of AD development and cognitive deterioration. However, as the research framework has shifted toward a biomarker-defined AD and alterations in specific biomarkers could take place years before cognitive decline becomes discernible, it is crucial to examine how HT influences AD biomarkers. The main goal of this study was to evaluate the impact of HT on AD biomarker-informed pathophysiology in both cognitively unimpaired (CU) and cognitively impaired (CI) post-menopausal females across the aging and AD spectrum.MethodsThis cross-sectional study included post-menopausal females without HT history (HT-) and with HT (HT+) at the time of PET imaging assessment from two cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants underwent magnetic resonance imaging (MRI), positron emission tomography (PET) and biofluid collection. Voxel-based t-tests were performed to assess the differences in amyloid-β (Aβ) and tau neurofibrillary tangles (NFTs) loads between HT- and HT + females. Linear regression models with interaction terms were also conducted to examine the interactive effects of HT and Aβ-PET on regional tau-PET.ResultsHT + females demonstrated significantly lower tau-PET standardized uptake value ratio (SUVR) in Braak I-II ROIs (P < 0.05, Hedges’ g = 0.73), Braak III-IV ROIs (P < 0.0001, Hedges’ g = 0.74) and Braak V-VI ROIs (P < 0.0001, Hedges’ g = 0.69) compared to HT- females. HT + females also showed significantly lower CSF p-tau181 (P < 0.001) and plasma p-tau181 (P < 0.0001) concentrations. Additionally, results from multivariate linear regression models indicated that HT interacts with cortical Aβ and is associated with lower regional NFT load.ConclusionsOverall, findings from this observational study suggest that HT is associated with lower tau neuroimaging and fluid biomarkers in postmenopausal females. Due to the close link between tau and cognition, this study highlights the need for large randomized controlled trials designed to systemically study the influences of HT on AD biomarkers and disease progression.

Comparative characteristics of the effectiveness of drugs for the treatment of alopecia areata in childhood

Alopecia areata (АА) is an autoimmune inflammatory disease with an established genetic predisposition, which is based on the lesion of hair follicles, leading to persistent or temporary hair loss. To date, treatment of АA in children, is limited to the use in most cases of external hormonal therapy in the form сream or the prescription of intradermal injections of GCS in outpatient conditions. However, data on the effectiveness of this group of drugs in severe forms of AA flow are not fully studied. There is an open question of the choice of the most preferred drug in patients simultaneously with a severe flow of AA and a severe form of atopic dermatitis. Another interesting variant of treatment of AA is the drug Dupilumab. (blocker IL-4 and IL-13). The mechanism of action of dupilumab at АA remains unknown, and its effect on TH-type 2 is assumed.Purpose of the study. To conduct a comparative performance characterization of: external GCS (Clobetazole) and injectable GCS (Betamethazone) for treatment of AA in children; Tofacitinib treatment for children with alopecia and the presence or absence of atopic dermatitis in the form of a concomitant disease; use of Dupilumaba to treat children with AA.Materials and methods. The research sample includes 420 patients. By the nature of the lesion, we considered three types of alopecia: spotted, total and universal. Patient data is taken from the register of AA patients in children. [13]. The effectiveness of the treatment was assessed on the scale SALT [14]. Patients were monitored for six months.Results. Use of intradermal injections GKS (Betamethazone), more effective than outdoor GKS (Clobetazole). In patients with atopic dermatitis, the efficacy of Tofacitinib for AA treatment is reliably higher than in patients without atopic dermatitis. Dupilumab may be a drug of choice for treating patients with a total and universal form of AA.Conclusion. Additional randomized controlled trials are needed to assess the long-term efficacy of drugs such as Tofacitinib and Dupilumab.

Synthesis, In vitro and In silico Studies of Novel bis-triazolopyridopyrimidines from Curcumin Analogues as Potential Aromatase Agents.

Breast cancer remains a major global health issue, particularly affecting women and contributing significantly to mortality rates. Current treatments for estrogen receptor-positive breast cancers, such as aromatase inhibitors, are effective but often come with side effects and resistance issues. This study addresses these gaps by targeting aromatase, an enzyme crucial for estrogen synthesis, which plays a pivotal role in breast cancer progression. The innovative approach involves synthesizing novel bis-triazolopyridopyrimidines, designed to leverage the combined pharmacological benefits of pyridopyrimidine and 1,2,4-triazole structures, known for their potent aromatase inhibition and anti-cancer properties. These compounds were synthesized and characterized using 1H-NMR, 13C-NMR, and MS spectral analyses, and their anticancer efficacy was evaluated through MTT assays against MCF-7 breast cancer cell lines in vitro. Molecular docking analyses revealed strong binding energies with aromatase, particularly for compounds 5 b, 5 c, 10 a, and 10 b, indicating their potential as effective aromatase inhibitors. The study highlights these compounds as promising candidates for further development as therapeutic agents against breast cancer.

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116).

To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time. Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results. BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.

To investigate the function of age-related genes in different subtypes of asthma based on bioinformatics analysis

Asthma is a heterogeneous airway inflammatory disease that can be classified according to the inflammatory phenotype. The pathogenesis, clinical features, response to hormone therapy, and prognosis of different inflammatory phenotypes differ significantly. This condition also refers to age-related chronic ailments. Here, we intend to identify the function of aging-related genes in different inflammatory phenotypes of asthma using bioinformatic analyses. Initially, the research adopted the GSEA analysis to understand the fundamental mechanisms that govern different inflammatory phenotypes of asthma pathogenesis and use the CIBERSORT algorithm to assess the immune cell composition. The differentially expressed genes (DEGs) of eosinophilic asthma (EA), neutrophilic asthma (NA), and paucigranulocytic asthma (PGA) were identified through the limma R package. Aging-related genes, screened from multiple databases, were intersected with DEGs of asthma to obtain the asthma-aging-related DEGs. Then, the GO and KEGG pathway enrichment analyses showed that the NA- and EA-aging-related DEGs are involved in the various cytokine-mediated signaling pathways. PPI network and correlation analysis were performed to identify and evaluate the correlation of the hub genes. Further, the clinical characteristics of asthma-aging-related DEGs were explored through ROC analysis. 3 and 12 aging-related DEGs in EA and NA patients show high diagnostic accuracy, respectively (AUC >0.7). This study provided valuable insights into aging-related gene therapy for phenotype-specific asthma. Moreover, the study suggests that effective interventions against asthma may operate by disrupting the detrimental cycle of “aging induces metabolic diseases, which exacerbate aging".

Subcutaneous vs Intravenous Trastuzumab/Pertuzumab: A Time and Motion Substudy of a Phase II Trial of Adjuvant Trastuzumab/Pertuzumab for Stage I HER2+ Breast Cancer (ADEPT trial).

The time required for in-clinic drug administration can substantially affect breast cancer patients' quality of life. Subcutaneous (SC) drug administration, as opposed to intravenous (IV), may reduce this time commitment. This study sought to estimate the difference in time burden between IV and SC administration of trastuzumab and pertuzumab (HP). We prospectively enrolled a subcohort of patients participating in the ADEPT trial (ClinicalTrials.gov identifier: NCT04569747, investigating adjuvant HP plus endocrine therapy for stage I human epidermal growth factor receptor 2-positive breast cancer) to this single-arm crossover time and motion substudy. Patients received two cycles of IV HP followed by two cycles of SC HP. During each cycle, time points in drug preparation and administration were captured. The primary end point was total patient time in the treatment chair. Additional end points included total patient treatment experience time and total pharmacy workflow time. A sample size of 22 patients was estimated to provide 90.7% power with two-sided alpha .05 to detect a difference of 70 minutes in the primary end point by treatment arm (IV v SC). Twenty-two patients were enrolled. The mean total patient time in the treatment chair was 61.8 minutes shorter with SC versus IV HP (22.5 v 84.3 minutes; P < .0001). The mean total patient treatment experience time (incorporating time spent waiting for treatment initiation and time spent in the treatment chair) was 81.8 minutes shorter for SC administration (96 v 177.8 minutes; P < .0001). The pharmacy workflow time was 78.2 minutes shorter for SC versus IV formulation (41 v 119.2 minutes; P < .0001). SC administration of HP shortened patient time burden by approximately 1 hour. SC drug administration can facilitate faster workflows for health care professionals and improve patients' breast cancer treatment experience.

Self-consistent signal transduction analysis for modeling context-specific signaling cascades and perturbations

Biological signal transduction networks are central to information processing and regulation of gene expression across all domains of life. Dysregulation is known to cause a wide array of diseases, including cancers. Here I introduce self-consistent signal transduction analysis, which utilizes genome-scale -omics data (specifically transcriptomics and/or proteomics) in order to predict the flow of information through these networks in an individualized manner. I apply the method to the study of endocrine therapy in breast cancer patients, and show that drugs that inhibit estrogen receptor α elicit a wide array of antitumoral effects, and that their most clinically-impactful ones are through the modulation of proliferative signals that control the genes GREB1, HK1, AKT1, MAPK1, AKT2, and NQO1. This method offers researchers a valuable tool in understanding how and why dysregulation occurs, and how perturbations to the network (such as targeted therapies) effect the network itself, and ultimately patient outcomes.

Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: a plain language summary of the monarchE study.

This article summarizes the most recent results of the monarchE study. This study was completed in participants with a type of breast cancer called HR+, HER2-, node-positive, high-risk early breast cancer. In this study, abemaciclib, a non-chemotherapy treatment, was administered with standard of care endocrine therapy after curative surgery. Most participants had received prior chemotherapy and/or radiotherapy. The study investigated if abemaciclib helped participants live longer without their cancer returning compared with participants who only received standard of care endocrine therapy. The study participants were assigned to 1 of 2 treatment groups. Participants in Group A were assigned to receive standard of care endocrine therapy with abemaciclib for 2years, followed by endocrine therapy for a total of at least 5years. Participants in Group B were assigned to receive standard of care endocrine therapy only for at least 5years. The effect of treatment was compared between these 2 groups. Overall, the results showed that the cancer was 34% less likely to come back after surgery in the participants in Group A (abemaciclib plus endocrine therapy) compared with those in Group B (endocrine therapy only). At 4years since the start of the study treatment, more participants who received the combination of abemaciclib plus endocrine therapy remained free of cancer compared with participants who received endocrine therapy alone (86% versus 79%). Participants who received abemaciclib plus endocrine therapy had more side effects than those who received endocrine therapy alone, but most of these effects were mild to moderate and reversible upon the end of therapy. The most common side effects in the abemaciclib group were diarrhea, infections, low number of white blood cells, and tiredness. This study found that administering abemaciclib in combination with standard endocrine therapy after curative breast surgery helped lower the risk of cancer returning in people with HR+, HER2-, node-positive, high-risk early breast cancer. Abemaciclib is a new treatment option for people with this diagnosis. People with high-risk early breast cancer should always talk to their doctors and nurses before making any decisions about their treatment.Clinical Trial Registration: NCT03155997 (monarchE study).