Tamoxifen for adults with hepatocellular carcinoma.

RATIONALE: Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent. OBJECTIVES: To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024. ELIGIBILITY CRITERIA: Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis. OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious. RISK OF BIAS: We assessed risk of bias using the RoB 2 tool. SYNTHESIS METHODS: We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE. INCLUDED STUDIES: We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years. SYNTHESIS OF RESULTS: Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials. AUTHORS' CONCLUSIONS: Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD014869.

Ospemifene and vulvovaginal atrophy: an update of the clinical profile for post-menopausal women.

INTRODUCTION: The demand for effective and safe treatments of genitourinary syndrome (GSM) in post-menopausal women (PMW) is growing. Published data on the efficacy and safety of ospemifene (OSP) prompt an updated literature review to enlighten possible improvements in the GSM treatment. AREA COVERED: We searched articles published in English from 2010 to 2023 through Medline (PubMed) and Embase databases with Boolean terms: OSP, PMW, GSM, endometrium, breast cancer, cardiometabolic syndrome, bone metabolism, adherence to treatment, and patient satisfaction. We selected randomized controlled trials (RCTs) and observational and cross-sectional studies and completed the search manually. EXPERT OPINION: Of the 157 retrieved records, 25 primary studies met the inclusion criteria (15 regarding efficacy and safety, two for additional effects, and four for adherence and satisfaction with the OSP treatment). Seven RCTs involved nearly 5,000 patients, 10 out of 18 prospective observational studies 563, and six retrospective analyses 356,439. Evidence of OSP treatment in PMW with GSM relies on RCTs and remarkable real-world data. The 25 primary studies showcased the high clinical response to symptoms, the favorable safety profile of OSP with very few adverse events, a neutral impact on the endometrium, breast, bone, and thrombosis, and the possible improvement of cardiovascular risk factors.

Drug exposure and risk factors of maculopathy in tamoxifen users.

Tamoxifen, a pivotal therapy for hormone receptor-positive breast cancer, is known for its efficacy in reducing breast cancer recurrence and mortality. However, concerns about potential ocular complications, particularly maculopathy, have emerged. This study aims to investigate the risk and associated factors of diverse macular conditions in tamoxifen users, considering drug exposure, demographics, and systemic diseases. A nationwide cohort of tamoxifen users, comprised of 14,267 tamoxifen users, was analyzed using the health insurance review and assessment database in South Korea. Demographic and clinical characteristics were examined, and the cumulative incidence of macular diseases was stratified by age and cumulative tamoxifen dosage. We conducted logistic regression analysis to identify potential risk factors among clinical variables such as age, sex, indications for tamoxifen use, and systemic diseases associated with various macular conditions. Additionally, Cox proportional hazard models were used to determine the baseline clinical characteristics predictive of these macular conditions, with subsequent calculation of hazard ratios. Cumulative incidences of overall macular diseases, other maculopathy excluding common macular diseases, and macular edema were 26.4, 11.4, and 6.5%, respectively. The incidence of various macular conditions increased with age and the cumulative tamoxifen dose. Age, cumulative dose group, and liver diseases demonstrated significant associations with overall macular diseases and maculopathy excluding common macular diseases in multivariate logistic regression analyses (all P < 0.05). Furthermore, age emerged as significant predictive factors of maculopathy in Cox proportional hazard models. Tamoxifen-induced maculopathy poses a concern for prescribing physicians and ophthalmologists, and this study provides valuable insights into its risk and risk factors. This study may contribute to evidence-based guidelines for tamoxifen maculopathy screening, emphasizing the importance of considering age, cumulative dose, and liver diseases for recommendation on screening timing and frequency.

Development of neuro-Behcet's disease in a patient with operable HER2-positive breast cancer during neoadjuvant chemotherapy: A case report.

BACKGROUND: Neuro-Behcet's disease (NBD) is a variant of Behcet's disease (BD). To our knowledge, there have been no previous reports on concurrent NBD in breast cancer patients undergoing chemotherapy. CASE PRESENTATION: Our patient had a history of BD and was asymptomatic. She was diagnosed with human epidermal growth factor receptor 2-positive breast cancer by core needle biopsy and was administered neoadjuvant chemotherapy. After four courses, in addition to the aggravation of the existing adverse events, headache, fever, dysarthria, and muscle weakness in the upper left and lower extremities appeared. On admission, she was diagnosed with acute NBD, and steroid therapy was initiated. After her symptoms improved gradually, she was discharged. Then, she underwent mastectomy and axillary lymph node dissection for breast cancer. Trastuzumab and pertuzumab plus tamoxifen were administered postoperatively. Two years postoperatively, no recurrence of breast cancer and NBD was noted. CONCLUSION: When chemotherapy is administered to breast cancer patients with a history of BD, it is necessary to select chemotherapy with as few adverse events as possible and to continue with treatment while paying attention to the risk of NBD.

Tamoxifen may contribute to preserve cardiac function in Duchenne muscular dystrophy.

Duchenne muscular dystrophy is life-limiting. Cardiomyopathy, which mostly ensues in the second decade of life, is the main cause of death. Treatment options are still limited. The TAMDMD (NCT03354039) trial assessed motor function, muscle strength and structure, laboratory biomarkers, and safety in 79 ambulant boys with genetically confirmed Duchenne muscular dystrophy, 6.5-12 years of age, receiving either daily tamoxifen 20 mg or placebo for 48 weeks. In this post-hoc analysis, available echocardiographic data of ambulant patients recruited at one study centre were retrieved and compared before and after treatment. Data from 14 patients, median 11 (interquartile range, IQR, 11-12) years of age was available. Baseline demographic characteristics were similar in participants assigned to placebo (n = 7) or tamoxifen (n = 7). Left ventricular end-diastolic diameter in the placebo group (median and IQR) was 39 (38-41) mm at baseline and 43 (38-44) mm at study end, while it was 44 (41-46) mm at baseline and 41 (37-46) mm after treatment in the tamoxifen group. Left ventricular fractional shortening in the placebo group was 35% (32-38%) before and 33% (32-36%) after treatment, while in the tamoxifen group it was 34% (33-34%) at baseline and 35% (33-35%) at study end. No safety signals were detected. CONCLUSION: This hypothesis-generating post-hoc analysis suggests that tamoxifen over 48 weeks is well tolerated and may help preserving cardiac structure and function in Duchenne muscular dystrophy. Further studies are justified. CLINICALTRIALS: gov Identifier: EudraCT 2017-004554-42, NCT03354039 What is known: • Duchenne muscular dystrophy (DMD) is life-limiting. Cardiomyopathy ensues in the second decade of life and is the main cause of death. Treatment options are still limited. • Tamoxifen reduced cardiac fibrosis in mice and improved cardiomyocyte function in human-induced pluripotent stem cell-derived cardiomyocytes. WHAT IS NEW: • In this post-hoc analysis of the TAMDMD trial among 14 boys, median 11 years of age, treated with either tamoxifen or placebo for 48 weeks, treatment was well-tolerated. • A visual trend of improved left-ventricular dimensions and better systolic function preservation generates the hypothesis of a potential beneficial effect of tamoxifen in DMD cardiomyopathy.

Development of a Web-Based Interactive Tool for Visualizing Breast Cancer Clinical Trial Tolerability Data.

PURPOSE: Longitudinal patient tolerability data collected as part of randomized controlled trials are often summarized in a way that loses information and does not capture the treatment experience. To address this, we developed an interactive web application to empower clinicians and researchers to explore and visualize patient tolerability data. METHODS: We used adverse event (AE) data (Common Terminology Criteria for Adverse Events) and patient-reported outcomes (PROs) from the NSABP-B35 phase III clinical trial, which compared anastrozole with tamoxifen for breast cancer-free survival, to demonstrate the tools. An interactive web application was developed using R and the Shiny web application framework that generates Sankey diagrams to visualize AEs and PROs using four tools: AE Explorer, PRO Explorer, Cohort Explorer, and Custom Explorer. RESULTS: To illustrate how users can use the interactive tool, examples for each of the four applications are presented using data from the NSABP-B35 phase III trial and the NSABP-B30 trial for the Custom Explorer. In the AE and PRO explorers, users can select AEs or PROs to visualize within specified time periods and compare across treatments. In the cohort explorer, users can select a subset of patients with a specific symptom, severity, and treatment received to visualize the trajectory over time within a specified time interval. With the custom explorer, users can upload and visualize structured longitudinal toxicity and tolerability data. CONCLUSION: We have created an interactive web application and tool for clinicians and researchers to explore and visualize clinical trial tolerability data. This adaptable tool can be extended for other clinical trial data visualization and incorporated into future patient-clinician interactions regarding treatment decisions.

Endocrine consequences of breast cancer therapy and survivorship.

Breast cancer survivorship is increasing, due to earlier diagnosis of the disease and more effective therapies. Long-term endocrine sequelae, including early menopause, bone health, fertility implications and menopausal symptoms, are important survivorship issues. Ovarian failure is common with chemotherapy and options for preserving fertility in young women include ovarian suppression during chemotherapy and oocyte or embryo cryopreservation before chemotherapy. Tamoxifen as adjunct therapy in premenopausal women leads to ovarian stimulation, sometimes ovulation and occasionally pregnancy with important teratogenic implications. Aromatase inhibitor therapy with or without gonadotrophin releasing hormone (GnRH) agonist leads to profound bone loss and anti-resorptive therapy is advised to prevent fracture. Tamoxifen acts to preserve bone in postmenopausal women but not premenopausal women. Pregnancy is not discouraged in young women with early breast cancer, even to the point of pausing adjunct therapy in order to conceive. However, menopausal hormone therapy is discouraged even years later. Non-hormonal therapy for menopausal symptoms in breast cancer survivors is available but, in some cases, estrogen-containing therapy may be worthy of consideration for quality of life in the informed patient.

Drug-induced liver injury secondary to tamoxifen.

Tamoxifen is a non-steroidal selective oestrogen receptor modulator commonly used in the treatment of breast cancer. It is associated with the development of fatty liver and steatohepatitis however drug-induced liver injury is rare. We report a woman in her 50s who developed malaise with an acute moderate aminotransferase elevation without jaundice 6 months after starting tamoxifen. She was not commenced on any other recent drugs and extensive investigation including infective and autoimmune liver screen, cross-sectional imaging and FibroScan were unremarkable. Liver biopsy revealed moderate lobular hepatitis with hepatocyte drop-out. Tamoxifen was ceased and the liver enzymes showed resolution over the following 3 months and improvement of her symptoms.

Tooth loss in breast cancer patients: A comparison between tamoxifen-treated and non-treated patients.

BACKGROUND: Tooth loss (TL) affects quality of life and general health. The literature suggesting that tamoxifen treatment in patients with breast cancer (BC) could be associated with alterations in oral health, increasing the risk of TL, is still scarce. This work aimed to determine the relationship between TL and tamoxifen consumption in patients with BC. MATERIAL AND METHODS: This cross-sectional observational study was carried out from July to September 2023 in the medical oncology services of the "Virgen de la Puerta" - ESSALUD High Complexity Hospital and "Dr. Luis Pinillos Ganoza" - IREN Norte - Regional Institute of Neoplastic Diseases, in Trujillo - Peru. Overall, 200 adult patients diagnosed with BC were evaluated, of which 100 consumed tamoxifen and 100 did not. Inter- and intra-rater reliability was determined with respect to TL, resulting in intra-class correlation values RHO = 0.971 and interclass RHO = 0.938. The oncologist of the corresponding service performed BC diagnosis and stage. Poisson regression was used to analyze results with a significance level of p<0.05. RESULTS: No relationship was found between TL and tamoxifen consumption in patients with breast cancer (p= 0.221); however, greater TL was observed in women who consumed tamoxifen for more than one year compared to those who did not use it (p=0.025) and in older adult women compared to young women (p=0.030). CONCLUSIONS: There is a relationship between TL and time of use of tamoxifen in patients with BC, concluding that patients who consumed tamoxifen for more than one year had greater TL than those who did not. Furthermore, no relationship was found between TL and cancer stages, but there was greater TL in older adult patients and also in those who consumed tamoxifen and did not receive chemotherapy or radiotherapy.

Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. METHODS: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. RESULTS: A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3 years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3 years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. CONCLUSIONS: Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3 years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.

Efficacy and safety of endoxifen in bipolar disorder: A systematic review.

BACKGROUND: Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes associated with bipolar disorder (BD). This review aims to assess the existing evidence base for endoxifen in BD treatment and evaluate the strengths and limitations of current research findings. METHODS: A systematic search was conducted on Medline, Embase, and Web of Science databases. We included studies published in English that used endoxifen in BD, alongside any relevant studies identified through manual searching and conference papers with full-text availability. Information pertaining to dose, duration, clinical effects, and safety profiles was extracted from the included studies. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in clinical trials. RESULTS: The final review included seven case reports (including two conference presentations), two clinical trials, and one prospective study. Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid substance use, and most patients received mood stabilizers concurrently. Few reports lacked any structured outcome measures. The clinical trials used divalproex 1000 mg as an active comparator, which was deemed sub-therapeutic. Despite being multicentric, the first trial lacked data on center-wise recruitment, and certain methodological concerns were observed across the included trials. There were no serious adverse effects noted, except for a significant elevation in lipid profile within a 3-week period. Limited data were available regarding endoxifen efficacy and safety in mixed episodes, depressive episodes, and maintenance treatment. CONCLUSION: There is a paucity of research on the efficacy and safety of endoxifen in BD. While existing evidence suggests short-term efficacy in manic episodes, significant limitations were identified in most of the included studies. Further research is imperative to establish the efficacy and safety of endoxifen in BD before considering its recommendation as a viable treatment option.

[Effects of extended aromatase inhibitors in women with hormone-dependent breast cancer who have already received five years of adjuvant hormone therapy: A systematic review and meta-analysis]. / Analyse des effets des inhibiteurs de l'aromatase en traitement prolongé chez les femmes ménopausées atteintes d'un cancer du sein non métastatique hormonodépendant ayant déjà reçu cinq ans d'hormonothérapie adjuvante : revue systématique et méta-analyse.

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.

Tamoxifen Dose De-Escalation: An Effective Strategy for Reducing Adverse Effects?

Tamoxifen, a cornerstone in the adjuvant treatment of estrogen receptor-positive breast cancer, significantly reduces breast cancer recurrence and breast cancer mortality; however, its standard adjuvant dose of 20 mg daily presents challenges due to a broad spectrum of adverse effects, contributing to high discontinuation rates. Dose reductions of tamoxifen might be an option to reduce treatment-related toxicity, but large randomized controlled trials investigating the tolerability and, more importantly, efficacy of low-dose tamoxifen in the adjuvant setting are lacking. We conducted an extensive literature search to explore evidence on the tolerability and clinical efficacy of reduced doses of tamoxifen. In this review, we discuss two important topics regarding low-dose tamoxifen: (1) the incidence of adverse effects and quality of life among women using low-dose tamoxifen; and (2) the clinical efficacy of low-dose tamoxifen examined in the preventive setting and evaluated through the measurement of several efficacy derivatives. Moreover, practical tools for tamoxifen dose reductions in the adjuvant setting are provided and further research to establish optimal dosing strategies for individual patients are discussed.

Hemostatic imbalance induced by tamoxifen in estrogen receptor-positive breast cancer patients: An observational study.

BACKGROUND: Estrogen receptor (ER)-positive (ER+) breast cancer accounts for approximately 75% of all breast cancers. Tamoxifen, a selective estrogen receptor modulator, is the standard adjuvant treatment. Although better tolerated than aromatase inhibitors, tamoxifen increases the risk of venous thromboembolism (VTE) 1.4-fold. AIM: To assess the hemostatic imbalance induced by tamoxifen in adjuvant treatment of ER+ breast cancer. METHOD: Twenty-five patients in remission from ER+ breast cancer under tamoxifen were included. One hundred and thirty one age- and BMI-matched healthy controls were included to establish reference ranges of thrombin generation assay (TGA) parameters. TGA was performed in the absence and presence of exogenous activated protein C (APC) to calculate the normalized APC sensitivity ratio (nAPCsr), a marker of APC resistance. RESULTS: All TG parameters except the endogenous thrombin potential (ETP) (-APC) were significantly impacted by tamoxifen (p < 0.001). In absence of APC, regardless of TGA parameters, at least 50% of results were outside the reference ranges except for ETP, which was above the upper reference limit in only two individuals. The most impacted parameter was the Peak Height with 52% (-APC) and 80% (+APC) of results above the upper reference range limit, respectively. The nAPCsr was significantly higher in tamoxifen users (mean ± standard deviation = 3.18 ± 0.91) compared to the control group (2.19 ± 0.92, p < 0.0001). CONCLUSION: This observational study showed that patients in remission from ER+ breast cancer taking tamoxifen had altered thrombin generation, as well as an acquired APC resistance. Moreover, this is the first study using the validated ETP-based APC resistance assay in tamoxifen-treated patients.

Using 3% retinol peeling and cosmeceuticals for the aesthetic wellness of the oncological patient after precautionary endocrine treatment: A case series.

BACKGROUND: Roughness, sagging, and skin rash are common in patients with breast cancer treated with LH-RH analog plus tamoxifen or aromatase inhibitors as adjuvant postsurgical endocrine therapy. The use of topical retinol (vitamin A) has shown to be an efficacious cosmetic treatment. AIMS: Peeling with an advanced retinol peel formulation based on 3% retinol, 4% triethyl citrate, 0.1% aminophil, bisabolol, and 1% vitamin E acetate, in a vehicle in an alcoholic solution has been successfully used to ameliorate skin appearance on subjects with photodamage and in the aged population. We aimed to verify its use during adjuvant chemotherapy. PATIENTS: Four subjects experiencing skin issues during postsurgical adjuvant therapy for their breast cancer received retinol peel at least 6 weeks after stopping their postsurgery therapy as a low invasive aesthetic medical treatment to be used both at the dermatology desk and at home. RESULTS: Retinol peel was effective, safe, and well-tolerated, improving skin brightness and firmness in all the patients, since 4 weeks after the beginning of the treatment. Patients declared to be satisfied with the treatment and their skin appearance letting them feel better for cancer recovery, too. CONCLUSION: These preliminary observations suggest that the use of an advanced retinol peel formulation might improve skin appearance in women experiencing skin damages caused by adjuvant therapy after breast cancer surgery.

Anastrozole as a therapeutic option for gynecomastia in a person receiving antiretroviral therapy: Case report.

A middle-aged Caucasian man living with HIV, clinically stable (viral load <20 copies/mL) on injectable antiretroviral cabotegravir plus rilpivirine every 2 months presented with a 6-month history of bilateral enlargement of the breasts associated with pain. His hormonal profile was normal, and no other underlying cause was identified. He was diagnosed with idiopathic gynecomastia. Tamoxifen is an anti-oestrogen recommended for gynecomastia and has been described in people living with HIV but can potentially induce the activity of cytochrome P450 3A4 (CYP3A4), reducing rilpivirine concentrations, which consequently may cause virological failure and resistance. This is the same for other antiretroviral agents majorly induced by CYP3A4. To date, there have been no reported cases of using anastrozole as a treatment for gynecomastia in people living with HIV or of its co-administration with antiretroviral. We describe the use of an aromatase inhibitor instead of tamoxifen in a person living with HIV, diagnosed with gynecomastia.

Tamoxifen in breast cancer and risk of Parkinson's disease: A meta-analysis.

BACKGROUND: Tamoxifen is widely used for hormone-sensitive breast cancer, achieved by modulating the estrogen receptor activity in a tissue-specific manner. There is evidence to support the protective effects of estrogen against Parkinson's disease (PD), a common neurodegenerative condition. Some epidemiologic studies suggest the use of tamoxifen may modulate the PD risk. We conducted a meta-analysis to examine the association between tamoxifen and risk of PD. METHODS: A search of PubMed using search terms synonymous with "tamoxifen" and "Parkinson's disease" was conducted. Outcomes of interest were the odds ratio (OR) of PD comparing tamoxifen-exposed to -unexposed women, as well as the incidence rate of PD in tamoxifen-exposed women. RESULTS: A total of 37,932 subjects with breast cancer, comprising 17,233 tamoxifen-exposed subjects and 20,699 tamoxifen-unexposed subjects, satisfied the inclusion criteria. The exposure to tamoxifen ranged from 30-96 months. Using the common-effect model, the pooled OR of PD was 2.4, with (95% CI 1.91-3.01, P < 0.0001), with high heterogeneity (I2 = 81.5%, Cochran's Q test P = 0.001). Pooling 28,640 tamoxifen-exposed patients under the common-effect model found an incidence rate of 5.86 events per 10,000 person-years (95% CI 4.82-7.12) with minimal heterogeneity (I2 = 26%, Cochran's Q test P = 0.258). CONCLUSIONS: Our meta-analysis suggests that tamoxifen use may be associated with an increased PD risk in women. However, due to heterogeneity and potential limitations of some of the studies, further clinical and functional validation will be needed. Longitudinal studies supported by imaging and biomarkers evaluation will be useful to identify the mechanisms linking tamoxifen and PD risk.

Tamoxifen retinopathy: A comprehensive review.

Tamoxifen is a selective estrogen receptor modulator used mainly for the treatment of breast cancer. Based on the case reports and studies performed to date on the retinal toxicity of tamoxifen, retinopathy appears to occur in as many as 12% of patients taking 20 mg tamoxifen a day for over 2 years. Of this 12%, as many as half develop symptomatic changes in visual acuity. Retinal changes consist primarily of crystalline deposits, cystoid macular edema, hyperreflective deposits in the inner retinal layers, and telangiectasia. Tamoxifen retinopathy is currently managed by discontinuing tamoxifen therapy as the cancer prognosis permits; however, discontinuing therapy demonstrates little to no improvement in visual acuity once visual changes have taken place. Intravitreal injections of steroids or antivascular endothelial growth factor therapy have been performed, but require further studying before conclusions can be made. Until then, optical coherence tomography screening for retinal changes should be performed every 6 months for patients who have been on tamoxifen therapy for 2 years or more. This way, patients can become aware of retinal changes, and their physicians can consider adjusting tamoxifen therapy before they risk developing changes in visual acuity.

Diabetes mellitus in breast cancer survivors: metabolic effects of endocrine therapy.

Breast cancer is the most common invasive malignancy in the world, with millions of survivors living today. Type 2 diabetes mellitus (T2DM) is also a globally prevalent disease that is a widely studied risk factor for breast cancer. Most breast tumours express the oestrogen receptor and are treated with systemic therapies designed to disrupt oestrogen-dependent signalling. Since the advent of targeted endocrine therapy six decades ago, the mortality from breast cancer has steadily declined; however, during the past decade, an elevated risk of T2DM after breast cancer treatment has been reported, particularly for those who received endocrine therapy. In this Review, we highlight key events in the history of endocrine therapies, beginning with the development of tamoxifen. We also summarize the sequence of reported adverse metabolic effects, which include dyslipidaemia, hepatic steatosis and impaired glucose tolerance. We discuss the limitations of determining a causal role for breast cancer treatments in T2DM development from epidemiological data and describe informative preclinical studies that suggest complex mechanisms through which endocrine therapy might drive T2DM risk and progression. We also reinforce the life-saving benefits of endocrine therapy and highlight the need for better predictive biomarkers of T2DM risk and preventive strategies for the growing population of breast cancer survivors.