Combined Hormone Therapy Research Articles

COMBINED HORMONE AND BRACHY THERAPIES FOR THE TREATMENT OF PROSTATE CANCER

Prostate cancer is a hormone-dependent cancer characterized by two types of cancer cells, androgen-dependent cancer cells and androgen-resistant ones. The objective of this paper is to present a novel mathematical model for the treatment of prostate cancer under combined hormone therapy and brachytherapy. Using a system of partial differential equations, we quantify and study the evolution of the different cell densities involved in prostate cancer and their responses to the two treatments. Numerical simulations of tumor growth under different therapeutic strategies are explored and presented. The numerical simulations are carried out on FreeFem++ using a 2D finite element method.

Metastatic castration-resistant prostate cancer-what are rational sequential treatment options?

In advanced prostate cancer, disease progression during ongoing androgen deprivation therapy (ADT) is referred to as castration-resistant prostate cancer (CRPC). Various therapeutic modalities are available for its treatment, including endocrine therapy, chemotherapy, poly (ADP-ribose) polymerase [PARP] inhibition, radionuclide therapy, and radioligand therapy. This review outlines practical aspects and considerations regarding treatment sequencing in mCRPC. The findings are based on existing prospective phase3studies that have demonstrated clinically relevant and statistically significant benefits in radiographically progression-free and/or overall survival. Sequential therapy, aside from numerous patient-specific factors, depends on the treatment patients received in the hormone-sensitive prostate cancer (mHSPC) setting. Following pretreatment with ADT alone or ADT plus docetaxel in the mHSPC context, additional endocrine therapy is the standard approach. In the event of progression under combined endocrine therapy initiated in the mHSPC setting, docetaxel currently serves as the standard for the majority of patients. Patients who received triplet therapy as apretreatment in the mHSPC scenario can be treated with radioligand therapy or second-line chemotherapy. Various active and well-tolerated treatment options are available for patients with metastatic castration-resistant prostate cancer (mCRPC). The choice of therapy is primarily determined by previous treatments, but many other individual factors are also taken into consideration.

Real-World Analysis of Clinical and Demographic Characteristics, Treatment Patterns, and Outcomes in Predominantly Older Patients with HR+/HER2- Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients. This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2- mBC receiving abemaciclib in US-based community oncology settings (1 September 2017 to 30 September 2019). Patients with other primary malignancies, clinical trial enrollment, and incomplete charts were excluded. Patient characteristics, treatment attributes and patterns, and real-world outcomes (clinical benefit rate [CBR] and stable disease among patients with response data available, time to chemotherapy [TTC], time to treatment discontinuation [TTD], and progression-free survival [PFS]) were summarized. Multivariable models evaluated the association between demographic/clinical characteristics and outcomes. Of the 448 final patients, 99% were female, with a median age of 67 years (25% were ≥75 years) and median follow-up of 11 months; most (60%) initiated abemaciclib within 2 years of mBC diagnosis. Patients received a median of 1(P25=0, P75=3) prior line of therapy for mBC before abemaciclib, including other CDK4 & 6is (48%) and prior chemotherapy (31%); most (57%) had visceral disease. The CBR for the overall population was 53%, with 48% achieving stable disease. The median TTC was not reached; median TTD was 249 days (95% confidence interval [CI]: 202, 304). The median PFS was 329 days (95% CI 266, 386). The discontinuation rate of abemaciclib owing to adverse events (30%) trended higher with age (years) (P=0.027): 18-49 (n=42; 19%), 50-64 (n=155; 25%), 65-74 (n=138; 32%), 75-84 (n=82; 37%), ≥85 (n=31; 49%); only 23% of patients overall had a dose hold or reduction prior to discontinuation. These patients were older than those in the MONARCH studies with substantial visceral disease, and prior chemotherapy and CDK4 & 6i use. Discontinuation rates were higher than in previous real-world studies (11.9%), highlighting the need for proactive management to optimize outcomes, particularly in older patients with mBC.

Efficacy and Safety of Anti-HER2 Targeted Therapy for Metastatic HR-Positive and HER2-Positive Breast Cancer: A Bayesian Network Meta-Analysis.

Despite the development of HER2-targeted drugs, achieving favorable outcomes for patients with HR+/HER2+MBC remains challenging. This study utilized Bayesian Network Meta-analysis to compare the efficacy and safety of anti-HER2 combination regimens. The primary analysis focused on progression-free survival (PFS), while secondary analyses included objective response rate, overall survival (OS) and the incidence rate of grade 3/4 adverse events (AEs). A comprehensive search across seven databases identified 25 randomized controlled trials for inclusion in this meta-analysis. For patients eligible for endocrinotherapy, our findings revealed that dual-target combined endocrine therapy, such as Her2-mAb+Her2-mAb+Endo (HR = 0.38; 95%CrI: 0.16-0.88) and Her2-mAb+Her2-tki+Endo (HR = 0.45; 95%CrI: 0.23-0.89), significantly improved PFS compared to endocrine therapy alone. According to the surface under the cumulative ranking curves (SUCRAs), Her2-mAb+Her2-mAb+Endo and Her2-mAb+Her2-tki+Endo ranked highest in terms of PFS and OS, respectively. For patients unsuitable for endocrine therapy, anti-HER2 dual-target combined chemotherapy, such as Her2-mAb+Her2-mAb+Chem (HR = 0.76; 95%CrI: 0.6-0.96) and Her2-mAb+Her2-tki+Chem (HR = 0.48; 95%CrI: 0.29-0.81), demonstrated significant improvements in PFS compared to Her2-mAb+Chem. The results were the same when compared with Her2-tki+Chem. According to the SUCRAs, Her2-mAb+Her2-tki+Chem and Her2-mAb+Her2-mAb+Chem ranked highest for PFS and OS, respectively. Subgroup analyses consistently supported these overall findings, indicating that dual-target therapy was the optimal approach irrespective of treatment line.

Current treatment landscape of HR+/HER2− advanced breast cancer in the Nordics: a modified Delphi study

Background This Delphi study aimed to assess current perspectives on hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2−) advanced breast cancer (aBC) treatment strategies across the Nordics, and to establish where consensus exists across the Nordics on HR+/HER2− aBC treatment. Material and methods A modified, three-round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection, and questionnaire development. The questionnaires covered relevant topics on HR+/HER2− aBC treatment: treatment patterns in different lines of therapy (first [1L], second [2L], and third [3L]), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics, and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement. Results In total, 28 experienced BC oncologists participated in the study from all five Nordic countries. Overall, topics reaching consensus included: preferred treatment approach in 1L and 2L therapy, treatment of oligometastatic disease, visceral crisis, brain metastases, and age-related treatment considerations. No consensus was reached for 3L therapy and local treatment for primary tumour in de novo aBC. Endocrine therapy (ET) combined with a cyclin-dependent kinase (CDK)4/6 inhibitor was the treatment of choice for 1L and 2L therapy. Treatment patterns in clinical practice did not always follow recommendations in current Nordic guidelines, as seen in the case of recently approved treatments. Discussion ET in combination with a CDK4/6 inhibitor is the preferred frontline treatment for HR+/HER2− aBC in the Nordics. The observed discrepancy between current guidelines and clinical practice could be due to differences in the reimbursement of novel treatments in the Nordics. Collaborative research efforts are warranted for topics that lack consensus.

Analysis of the regional clinical use of CDK4/6 inhibitor ribociclib as a mechanism of integration of a research approach in drug provision

Introduction. Implementation of data from registration studies into clinical practice often presents a number of problems due to the heterogeneity of the patient population, the lack of uniformity of thinking among clinicians, and organizational difficulties. Using the example of studying the algorithm for prescribing ribociclib in a cohort of patients from one region in modern realities and the possibilities of drug provision, we have shown the main controversial points in the implementation of the results of clinical trials in the daily practice of an oncologist.Aim. The purpose of this study was to analyze our own preliminary results of the treatment of patients with hormone-receptorpositive Her-2-negative metastatic breast cancer using ribociclib in the routine practice of prescribing CDK4/6 inhibitors outside of clinical trials, taking into account the peculiarities of regional drug supply.Materials and methods. A retrospective analysis of the results of treatment of patients (n = 56) who took ribociclib in terms of combined hormone therapy for metastatic hormone-dependent Her-2 negative breast cancer in the practice of oncologists in the Krasnodar Territory from 2019 to 2022 was carried out.Results. At the time of data collection and analysis, with a total follow-up time of 29 months, the median overall survival was not achieved, 52 patients (92.9%) were alive and continued to follow up. The median progression-free survival was also not reached: disease progression was recorded in 19 patients (33.9%), 37 patients (66.1%) continued treatment. A total of 14 out of 56 patients (25.1%) received ribociclib therapy in combination with drugs for endocrine therapy in the first and second lines. The best results were demonstrated by patients with a high level of expression of progesterone receptors in the tumor (p = 0.005), a low level of Ki67 proliferative activity index (p = 0.035), without metastatic visceral lesions (p = 0.034), who received the minimum number of lines of therapy before the appointment of ribociclib (p = 0.029). The results of the clinical part of the study became available due to the timely optimization of regional drug supply processes with the creation and constant monitoring by clinicians of a stable cohort of patients in the form of updated registers.Conclusions. The introduction of the experience and knowledge of clinical oncologists into the process of drug supply management and its optimization, taking into account the understanding of data on drug efficacy and toxicity, is a promising direction and requires further discussion.

Co-targeting RANK pathway treats and prevents acquired resistance to CDK4/6 inhibitors in luminal breast cancer

The combination of endocrine therapy (ET) and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) was a hallmark in metastatic luminal breast cancer (BC). However, intrinsic and acquired resistance affects long-term efficacy. Here, we study the role of the receptor activator of nuclear factor-κB (RANK) pathway in CDK4/6i resistance. We find that RANK overexpression in luminal BC is associated with intrinsic resistance to CDK4/6i, both invitro and in mouse xenografts, and decreased proliferation rate and chronic interferon (IFN) γ response are highlighted as resistance drivers. Gene expression data from the NeoPalAna CDK4/6i clinical trial, and studies with palbociclib-resistant cell lines, show that RANK is upregulated after treatment with CDK4/6i, supporting a role in acquired resistance. Our study shows that RANK ligand (RANKL) inhibitors can restore sensitivity to CDK4/6i and prevent acquired resistance. On the basis of these findings, we conclude that pharmacological inhibition of the RANK pathway through RANKL blocking could represent an add-on to ET+ CDK4/6i, warranting further clinical studies.

Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study.

To assess the risk of select safety outcomes including endometrial cancer, endometrial hyperplasia, and breast cancer among women using conjugated estrogens/bazedoxifene (CE/BZA) as compared with estrogen/progestin combination hormone therapy (EP). We conducted a new-user cohort study in five US healthcare claims databases representing more than 92 million women. We included CE/BZA or EP new users from May 1, 2014, to August 30, 2019. EP users were propensity score (PS) matched to users of CE/BZA. Incidence of endometrial cancer, endometrial hyperplasia, breast cancer, and eight additional cancer and cardiovascular outcomes were ascertained using claims-based algorithms. Rate ratios (RR) and differences pooled across databases were estimated using random-effects models. The study population included 10,596 CE/BZA and 33,818 PS-matched EP new users. Rates of endometrial cancer and endometrial hyperplasia were slightly higher among CE/BZA users (1.6 and 0.4 additional cases per 10,000 person-years), although precision was limited because of small numbers of cases (endometrial cancer: RR, 1.50 [95% confidence interval {CI}, 0.79-2.88]; endometrial hyperplasia: RR, 1.69 [95% CI, 0.51-5.61]). Breast cancer incidence was lower in CE/BZA users (9.1 fewer cases per 10,000 person-years; RR, 0.79; 95% CI, 0.58-1.05). Rates of other outcomes were slightly higher among CE/BZA users, but with confidence intervals compatible with a wider range of possible associations. CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the first years of use.

The association between menopausal hormone therapy and gastroesophageal reflux disease: a systematic review and meta-analysis.

Gastroesophageal reflux disease (GERD) is a chronic condition associated with several risk factors, but little is known about the association between hormone therapy (HT) and GERD in postmenopausal women. We investigated the association between ever or current menopausal HT use and GERD using a systematic review and meta-analysis. Studies published between 2008 and August 31, 2022, were pooled using a DerSimonian and Laird random-effects model, and outcomes were reported as adjusted odds ratios (aOR) with a corresponding 95% CI. The pooled analysis of five studies found a significant direct association between estrogen use and GERD (aOR, 1.41; 95% CI, 1.16-1.66; I2 = 97.6%), and progestogen use and GERD (two studies: aOR, 1.39; 95% CI, 1.15-1.64; I2 = 0.0%). The use of combined HT was also associated with GERD (1.16; 95% CI, 1.00-1.33; I2 = 87.9%). Overall, HT use was associated with 29% higher odds for GERD (aOR, 1.29; 95% CI, 1.17-1.42; I2 = 94.8%). The large number of pooled participants, differences in study design, geography, patient characteristics, and outcome assessment resulted in significant high heterogeneity. There is a significant association between ever or current HT use and GERD. However, the results should be interpreted with caution, given the small number of included studies and high heterogeneity. This warrants careful evaluation of GERD risk factors when prescribing HT to reduce the risk of potential GERD complications.

Histological, Laboratorial, and Clinical Benefits of an Optimized Maintenance Strategy of a Potential Organ Donor-A Rabbit Experimental Model.

Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.

O-027 Efficacy results from a phase 3, randomized, placebo-controlled trial testing two doses of linzagolix in women with endometriosis-associated pain

Abstract Study question Does once-daily linzagolix for up to 6 months reduce the pain symptoms in women with endometriosis? Summary answer Once-daily oral use of the GnRH agonist linzagolix alone or in combination with combined hormonal add-back therapy (ABT) for 24 weeks improved endometriosis-associated pain symptoms. What is known already Linzagolix is an oral GnRH antagonist under development to treat endometriosis-associated pain (EAP). In the EDELWEISS 3 study linzagolix 200mg+ABT met its co-primary endpoints at 3 months by reducing dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) in a clinically meaningful fashion along with a stable or decreased use of analgesics. Linzagolix 75mg significantly reduced DYS but not NMPP. Secondary endpoints were DYS, NMPP, overall pelvic pain, dyschezia, and dyspareunia at 6 months assessed with a numeric and/or verbal rating scale (NRS and/or VRS), and interference of pain with daily activities assessed with the Endometriosis-Health-Profile-30 (EHP-30) pain domain. Study design, size, duration EDELWEISS 3 was a randomized, double-blind, placebo-controlled Phase 3 study, investigating efficacy and safety of linzagolix 75mg and linzagolix 200mg with ABT (1mg estradiol/0.5mg norethindrone acetate) for up to 24 weeks in women with moderate to severe EAP. To qualify, subject had to demonstrate over 2 menstrual cycles at least moderate DYS and NMPP for ≥2 days each and at least moderate overall pelvic pain for ≥5 days. Participants/materials, setting, methods Eligible women with moderate to severe EAP were equally randomized to once daily oral: placebo, linzagolix 75mg or linzagolix 200mg+ABT. Efficacy assessments included DYS, NMPP, dyspareunia (assessed with a 4-point VRS), overall pelvic pain and dyschezia (assessed with an 11-point NRS), and interference of pain with daily activities (assessed with the EHP-30 pain domain). The co-primary endpoint was a responder analysis at Month 3. We present secondary endpoints at Month 6. Main results and the role of chance Participants (n = 484) had a mean age of 35 years, a BMI of 24kg/m2 with 99% of subjects being White. At Month 6, compared to placebo significant improvements in DYS and NMPP (VRS) were observed in the 200mg+ABT group, with an estimated mean change from baseline (CfB) of -1.83 (95%CI: 1.96, 1.70; difference with placebo p < 0.001) and 0.92 (95%CI: 1.03, 0.82; p = 0.002), respectively. For the 75mg group, the mean CfB was 1.10 (95%CI: 1.23; 0.97; p < 0.001) and 0.84 (95%CI: 0.95; 0.73; p = 0.048), respectively. For overall pelvic pain (NRS), marked improvements were observed with an estimated mean CfB of 3.39 (95%CI: 3.74, 3.03; p < 0.001) for 200mg+ABT and 2.84 (95%CI: 3.20, 2.48; p = 0.024) for 75mg. Similarly, dyschezia (NRS) was significantly improved for both groups with a mean CfB of 1.99 (95%CI: 2.29, 1.70; p = 0.012) for 200mg+ABT and -1.98 (95%CI: 2.28, 1.69; p = 0.015) for 75mg. Both doses offered a marked, statistically significant improvement in the interference of pain with daily activities as measured on the EHP-30 Pain Dimension, with an estimated mean CfB of 35.60 (95%CI: 38.73, 32.48; p < 0.001) and -27.37 (95%CI: 30.50, 24.25; p = 0.001) for the 200mg+ABT and 75mg group, respectively. Both doses did not provide significant improvements in dyspareunia. Limitations, reasons for caution We report data of the EDELWEISS 3 study for up to Month 6. An extension study of this trial will provide more information on the sustained effect and potential symptom recurrence after stopping treatment. Wider implications of the findings The linzagolix 200mg+ABT group provided substantial improvement in endometriosis-associated pain symptoms. The 75mg dose was less effective but demonstrated still marked improvements. There exists an substantial need for different treatment regimens in women suffering from endometriosis. Trial registration number NCT03992846

Survival Outcomes in Patients With Hormone Receptor–Positive Metastatic Breast Cancer With Low or No ERBB2 Expression Treated With Targeted Therapies Plus Endocrine Therapy

Approximately 45% to 60% of hormone receptor (HR)-positive metastatic breast cancer (mBC) shows a low-level expression of ERBB2. Low ERBB2 expression is defined as ERBB2 immunohistochemical expression of 1+ or 2+ with a negative ERBB2 amplification by in situ hybridization. The efficacy of the antibody-drug conjugate trastuzumab deruxtecan in low-ERBB2, HR-positive mBC has been practice changing. However, there are conflicting data on the prognostic value of low ERBB2 expression in HR-positive mBC and whether low ERBB2 expression is a separate entity. To examine whether outcomes differ by immunohistochemical analysis for patients with HR-positive mBC with low ERBB2 expression vs those without ERBB2 expression when treated with targeted therapy (TT) plus endocrine therapy (ET). This single-institution cohort study used prospectively collected electronic data from the MD Anderson Cancer Center for patients with a diagnosis of HR-positive mBC treated with ET in combination with a TT (cyclin-dependent kinase 4/6 inhibitors [CDK4/6is], everolimus, or alpelisib) between January 1, 2010, and December 31, 2021. HR-positive mBC with either low or no ERBB2 expression. The main outcomes were median progression-free survival and overall survival. Data on demographic characteristics, estrogen and progesterone receptor status, ERBB2 status, histologic subtype, menopausal status, treatment duration, and survival status were collected. A total of 1585 women (median [range] age, 51 [24-92] years) were included in the study. Of these women, 1013 (63.9%) had mBC with low ERBB2 expression and 572 (36.1%) had mBC with no ERBB2 expression. A total of 1084 (68.4%) were treated with a CDK4/6i (912 patients were treated in the first line and 172 were treated in the second line); 475 (30.0%) received everolimus and 26 (1.6%) received alpelisib. In the patients who received a first-line CDK4/6i, 618 (67.8%) received an aromatase inhibitor as their ET backbone and 265 (29.1%) received fulvestrant. With a median follow-up time of 17.9 months (range, 1-111 months), progression-free survival and overall survival were not statistically different between the patients with low and no ERBB2 expression treated with TT plus ET. In this cohort study of patients with HR-positive mBC treated with TT plus ET, low ERBB2 expression did not have a significant association with prognosis.

Case Series of Ischemic Stroke occurring in Male- to- Female Transgender population on Gender - Affirming Hormonal Therapy and Review of the Literature (P2-5.022)

<h3>Objective:</h3> To stress the importance of individualized vascular risk assessment and shared decision-making to continue Gender-Affirming Hormonal therapy (GAHT) in the Male to Female (MTF) transgender population following ischemic stroke with review of the literature. <h3>Background:</h3> Transgender individuals have higher mental health burden and suicide rates. GAHT is the standard of care for transgender individuals suffering from symptoms of gender dysphoria. Estrogen therapy has been associated with increased stroke risk, but its specific contribution is poorly characterized and appears to be impacted by the route of administration. <h3>Design/Methods:</h3> We include three self-identified MTF transgender patients who had taken GAHT and treated for ischemic stroke inpatient or were seen for stroke follow-up. Data was gathered from chart review including demographics, vascular risk factors, type of GAHT, clinical course, and outcomes. <h3>Results:</h3> Two MTF transgender patients on GAHT were treated inpatient for an acute stroke and one was seen in follow up. At the time of infarct, one MTF transgender patient was on combination hormonal therapy, one patient was on combination hormonal therapy and spironolactone, and one patient was on estrogen hormonal therapy of unknown type. Traditional vascular risk factors were present in the patient population prior to ischemic stroke including: hypertension, hyperlipidemia, type 2 diabetes mellitus, morbid obesity, prior ischemic stroke, tobacco use disorder, alcohol use disorder. <h3>Conclusions:</h3> Each patient in our small series had traditional vascular risk factors in addition to GAHT use prior to ischemic infarct. Identifying and treating comorbid vascular risk factors in MTF transgender patients prior to and during GAHT is essential to decrease ischemic stroke risk. Additional studies are needed to determine the relative impact of GAHT on stroke risk. Given mental health burden of gender dysphoria symptoms, shared decision-making is necessary to determine risks and benefits of continuing GAHT after ischemic stroke in MTF transgender patients. <b>Disclosure:</b> Ms. Giovannini has nothing to disclose. An immediate family member of Dr. Ivan has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Cellular and Molecular Medicine. An immediate family member of Dr. Ivan has received intellectual property interests from a discovery or technology relating to health care. Dr. Karel has nothing to disclose.

Autoimmune glial fibrillary acidic protein astrocytopathy: clinical analysis and review of 15 cases

BackgroundTo review clinical characteristics, auxiliary examination results, treatment effects, and outcomes of patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).MethodsWe collated and retrospectively analyzed clinical data of 15 patients admitted with clinical characteristics of an autoimmune GFAP-A acute encephalitis or meningitis phenotype.ResultsAll patients were diagnosed with acute-onset meningoencephalitis and meningoencephalomyelitis. Initial presentations included pyrexia and headache at onset; dual symptoms of prominent tremor with urinary and bowel dysfunction; ataxia, psychiatric and behavioral abnormalities, and impaired consciousness; neck resistance; reduced extremity muscle strength; blurred vision; epileptic seizures; and reduced basic blood pressure. Cerebrospinal fluid (CSF) examination showed that the degree of protein elevation was significantly higher than the degree of increase in white blood cells. Moreover, in the absence of obvious low chloride and glucose levels, CSF chloride levels decreased in 13 patients, accompanied by a CSF glucose level decrease in four. Brain abnormalities were found in magnetic resonance imaging of ten patients, with a linear radial perivascular enhancement present in the lateral ventricles of two patients and symmetric abnormalities in the splenium of the corpus callosum in three patients.ConclusionsAutoimmune GFAP-A may be a spectrum disorder, with acute- or subacute-onset meningitis, encephalitis, and myelitis being the main phenotypes. When used for acute stage treatment, combined hormone and immunoglobulin therapy was superior to hormone pulse therapy or immunoglobulin pulse therapy alone. However, hormone pulse therapy alone without immunoglobulin pulse therapy was associated with a greater number of remaining neurological deficits.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Abstract 4364: Cost-effectiveness analysis of abemaciclib and endocrine therapy combination for the adjuvant treatment of HR+/HER2-, node-positive, high-risk, early breast cancer

Abstract Background: Abemaciclib is the only approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved for adjuvant treatment of hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-), node-positive, high-risk early breast cancer (EBC) patients. However, the addition of abemaciclib to the standard of care endocrine therapy (ET, such as tamoxifen or aromatase inhibitors) results in a drastic increase to the overall healthcare costs. Objective: In this study, we aimed to evaluate the cost-effectiveness of abemaciclib and ET combination versus ET monotherapy for the adjuvant treatment of HR+/HER2-, EBC from the U.S. third-party payer perspective. Methods: A Markov-based decision analytic model using TreeAge Software was developed. The model simulated lifetime costs and health outcomes over a lifetime. The model incorporated the disease course of the progression-free disease, progressive disease, death due to disease, and mortality due to other causes. All clinical data and utilities were derived from the literature and clinical trial: monarchE. Notable adverse events such as neutropenia, leucopenia, anemia, and diarrhea were included. Age-specific mortality risk was calculated from the U.S. life tables. The outcomes were measured by costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The willingness-to-pay threshold was set at $100,000 per QALY gained. Results: We simulated our analysis on patients assigned to either abemaciclib + ET or ET alone groups as per the monarchE trial. The median age of the patients was 51 years. In base case analysis, the total costs for abemaciclib plus ET and ET alone treatment, were USD 122,052.11 and USD 40,344.87, respectively. Abemaciclib plus ET treatment produced 4.5 QALYs, while the ET treatment alone produced 4.31 QALYs. Overall, abemaciclib plus ET was marginally more effective than ET with an additional 0.20 QALYs but much costlier with an ICER of $417,780.18/QALY. For utilities ranging from 0.41 to 0.69, the ICERs ranged from USD 36,5950 to USD 4,463,866.59 per QALY, which exceeded the WTP threshold. Using probabilistic sensitivity analysis, we estimated that the combination of abemaciclib plus ET was a cost-effective strategy at the willingness-to-pay threshold of $500,000 per QALY or higher for the base case population. Conclusion: At current costs, abemaciclib plus ET is not cost-effective as compared to ET monotherapy for patients with node-positive, high-risk, HR+/HER2- EBC in the US healthcare system from the third-party payer perspective. Citation Format: Ashna Talwar, Ashish Deshmukh, Meghana Trivedi, Rajender R. Aparasu. Cost-effectiveness analysis of abemaciclib and endocrine therapy combination for the adjuvant treatment of HR+/HER2-, node-positive, high-risk, early breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4364.

Advances in Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer.

To provide an overview of the current management of hormone receptor-positive (HR +) advanced breast cancer as well as highlight ongoing clinical investigation and novel therapies in development. CDK4/6 inhibition plus endocrine therapy is standard front-line therapy for HR + advanced breast cancer. Continuation of CDK4/6 inhibitors in combination with alternative endocrine therapy has been evaluated in the second-line setting. Alternatively, endocrine therapy in combination with PI3K/AKT pathway targeting agents has been studied, particularly in patients with PI3K pathway alterations. The oral SERD elacestrant has also been evaluated in patients with ESR1 mutation. Many novel endocrine agents and targeted agents are in development. An improved understanding of combination therapies and sequencing of therapies is needed to optimize the treatment paradigm. Biomarker development is needed to guide treatment decisions. Advances in the treatment of HR + breast cancer have resulted in improved patient outcomes in recent years. Continued development efforts with identification of biomarkers to better understand response and resistance to therapy are needed.

MP79-08 EFFECT OF HORMONE THERAPY ON SEMEN ANALYSIS PARAMETERS IN ADOLESCENT TRANSGENDER FEMALES

You have accessJournal of UrologyCME1 Apr 2023MP79-08 EFFECT OF HORMONE THERAPY ON SEMEN ANALYSIS PARAMETERS IN ADOLESCENT TRANSGENDER FEMALES Sai Allu, Sreeya Komaravolu, Mark Sigman, Gabriella Avellino, and Sarah Moore Sai AlluSai Allu More articles by this author , Sreeya KomaravoluSreeya Komaravolu More articles by this author , Mark SigmanMark Sigman More articles by this author , Gabriella AvellinoGabriella Avellino More articles by this author , and Sarah MooreSarah Moore More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Feminizing transgender patients represent an important urological patient population with unique healthcare needs. Although not every patient chooses to cryopreserve, everyone should be given the option. Hormone therapy (HT) is often started prior to proceeding with surgical orchiectomy. Research has suggested that transgender females on HT have reduced semen analysis (SA) parameters compared to cisgender patients, including reduced sperm concentration and motility. [1,2] There is limited information regarding fertility preservation by transgender patients on HT. The goal of this study is to report cryopreservation outcomes by adolescent feminizing transgender patients who are currently on HT. METHODS: We retrospectively reviewed charts of donors with our Men’s Health Center for direct donations to the sperm bank between 01/2011 to 07/2022. Inclusion criteria included adolescent age (16–24 years old) and the use of HT within three months of cryopreservation. Patient data collected included patient demographics, type of hormone therapy, and SA parameters. RESULTS: Five transgender patients were found who were on HT within three months prior to their semen cryopreservation and analysis. Their median age was 18 (range 16–22). Three patients were on spironolactone, one patient was on estradiol, and one patient was on a combination of both medications. All four patients on single-medication HT had normal concentration and motility on their semen analysis, as defined by the WHO Laboratory Manual for the Examination and Process of Human Semen (Table 1). Three of four patients on single HT had normal volume. The patient on combination HT demonstrated lowered overall SA parameters. CONCLUSIONS: This is the largest cohort of adolescent feminizing transgender patients on hormone therapy in which fertility preservation has been described. Semen cryopreservation could be a viable method for fertility preservation among this patient population who have already initiated hormonal therapies, specifically spironolactone or estradiol. Patients on single HT appear to have improved semen analysis parameters compared to patients on combination HT. Future studies are needed to further characterize fertility preservation with specific information on duration and dosage of HT, as well as outcomes of cryopreservation. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1144 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sai Allu More articles by this author Sreeya Komaravolu More articles by this author Mark Sigman More articles by this author Gabriella Avellino More articles by this author Sarah Moore More articles by this author Expand All Advertisement PDF downloadLoading ...

Childbirth after perioperative systemic therapy in patients with breast cancer: a retrospective single institutional study in Japan.

The number of breast cancer patients of childbearing age has been increasing. Therefore, we investigated the characteristics and the childbearing status of the patients who received systemic therapy for breast cancer during their childbearing age to better understand the clinical impact of childbirth. Female patients with breast cancer younger than 40years old who underwent surgery and received perioperative systemic therapy from 2007 to 2014 were included in this study. We compared the characteristics of patients with and without childbirth after treatment. Of 590 patients, 26 delivered a child, and 355 did not bear a child during the median observation period of 8.1years, whilst 209 had unknown childbirth data. The childbirth group had a lower mean age at surgery (32.2 vs. 35.1, P<0.001). The proportion of patients who desired childbirth and used assisted reproductive technology was significantly higher in the childbirth group (65.4 vs. 23.9% and 45.2 vs. 5.1%, respectively, P<0.001). The patients in the childbirth group had significantly less advanced disease (P=0.002). In the childbirth group, the age at childbirth was significantly older in patients who received combined endocrine therapy and chemotherapy (40.8years) than in patients who received either alone (endocrine therapy: 36.9years, chemotherapy: 36.7years, P=0.04). However, survival was not different between those with and without childbirth. It is critical to recognize the desire for childbirth in patients with breast cancer who are receiving systemic therapy and to provide them with necessary fertility information before treatment to support their decision-making.

Abstract GS1-07: Results from a phase III randomized, placebo-controlled clinical trial evaluating adjuvant endocrine therapy +/- 1 year of everolimus in patients with high-risk hormone receptor-positive, HER2-negative breast cancer: SWOG S1207

Abstract BACKGROUND: Abnormalities of the PI3kinase/AKT/mTOR signaling network are common in breast cancer (BC) and are associated with endocrine resistance. Everolimus, an mTOR-inhibitor increased PFS when combined with endocrine therapy (ET) in the metastatic setting and is thought to revert endocrine resistance. S1207 is a phase III randomized, placebo-controlled trial evaluating the role of everolimus in combination with ET in the adjuvant setting among patients with high-risk hormone receptor-positive, HER2-negative BC (NCT01674140). METHODS: Eligible patients were &amp;gt;18 years of age with histologically confirmed invasive hormone receptor-positive and HER2-negative high-risk BC. Four risk groups were defined as: 1) &amp;gt; 2cm node-negative disease (or pN1mi), and either an Oncotype DX® Recurrence Score (RS) &amp;gt; 25 or MammaPrint® high-risk category (MP high); 2) 1-3 positive nodes and either RS &amp;gt;25, MP high or a pathological grade 3 tumor; 3) &amp;gt;4 positive lymph nodes. Patients treated with neoadjuvant chemotherapy were eligible if: 4) after surgery had &amp;gt;1 lymph node involvement. Patients were randomized 1:1 to physician’s choice adjuvant ET in combination with one year of everolimus (10 mg PO daily) or ET plus placebo stratified by risk group. The primary endpoint was invasive disease-free survival (IDFS) evaluated by a stratified log-rank test. Secondary endpoints included overall survival (OS) and safety. The hazard ratio (HR) for treatment efficacy was estimated using Cox regression with stratification by risk groups. Subset analyses included preplanned evaluation within risk group and exploratory analyses of menopausal status and age. RESULTS: 1,939 patients were randomized between September 2013 and May 2019, of them 1,792 were eligible and included in the analysis (896 per arm). Primary reason for ineligibility was timing after chemotherapy/radiation or not high risk. Median age was 54 years (22-85) and 32% were premenopausal. With a median follow-up of 50.5 months, there were 389 IDFS events as of May 2022 (data cutoff). 5-year IDFS was 74.8% among patients treated with everolimus and 73.9% among patients treated with placebo, HR=0.93 (95% CI 0.76-1.14). However, the proportional hazards assumption was violated (p=0.02) suggesting differential treatment effect over time. The HR during the one year of treatment was 0.72 (95% CI 0.47-1.10) while after one year it was 1.00 (95% CI 0.80-1.26). The 5-year OS was 87.6% in the everolimus arm and 85.5% in the placebo arm, HR=0.98 (95% CI 0.75-1.28). Analysis by risk group did not show higher everolimus benefit as risk increased. No difference in IDFS or OS was seen among postmenopausal patients (IDFS HR=1.08 [95% CI 0.85-1.36], OS HR=1.19 [95% CI 0.87-1.61]). Among premenopausal patients, everolimus was associated with improved IDFS (HR=0.63 [95% CI 0.43-0.93]) and OS (HR=0.48 [95% CI 0.26-0.88]). Treatment completion of randomized therapy was lower in the everolimus arm compared to placebo (47.9% v 72.7%). Grade 3 and 4 toxicities were noted in 6.5% and 0.5% of patients in the placebo arm and in 31.2% and 3.7% in the everolimus arm respectively. CONCLUSIONS: Addition of one year of adjuvant everolimus to standard adjuvant ET did not improve IDFS or OS and was associated with low completion rate and increased AEs. Among premenopausal patients there was a benefit in IDFS and OS that is hypothesis generating. Future translational studies will evaluate potential predictors of everolimus benefit and drug toxicity. Citation Format: Marianna Chavez, Jieling Miao, Lajos Pusztai, Matthew P. Goetz, Priya Rastogi, Patricia A. Ganz, Eleftherios (Terry) Mamounas, Soonmyung Paik, Hanna Bandos, Wajeeha Razaq, Anne O’Dea, Virginia Kaklamani, Andrea L.M. Silber, Lisa E. Flaum, Eleni Andreopolu, Joseph Baar, Albert G. Wendt, Jennifer F. Carney, Priyanka Sharma, Julie R. Gralow, Danika L. Lew, William E. Barlow, Gabriel N. Hortobagyi. Results from a phase III randomized, placebo-controlled clinical trial evaluating adjuvant endocrine therapy +/- 1 year of everolimus in patients with high-risk hormone receptor-positive, HER2-negative breast cancer: SWOG S1207 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-07.