Tamoxifen induces biochemical responses in Pacific oysters Magallana gigas (Thunberg, 1793) at environmentally relevant concentrations.

The activities of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), and glutathione-S-transferase (GST) were evaluated in the gills (GI) and digestive gland (DG) of Magallana gigas oysters exposed to tamoxifen (TAM) at environmental concentrations of 10 and 100 ng L-1 for 1 and 4 days. A higher CAT activity in the GI and DG and higher GPx activity only in the DG was observed of oysters exposed to both concentrations after 1 day. Furthermore, a significant increase in GR and G6PDH, was detected in the DG after 1 day of exposure to 10 ng L-1 and only G6PDH activity increase after 1 day of exposure to 10 ng L-1 in the GI. This suggests that the DG is a tissue more sensitive to TAM exposure and was confirmed with the individual Integrated Biomarker Response version 2 index (IBRv2i), highlighting the acute stress caused by TAM and a cellular adaptation.

Antitumor effects of co-treatment of resveratrol with antitumor drugs in ER- and HER2-positive breast cancer cells are due to induction of apoptosis and modulation of estrogen receptor expression.

BACKGROUND: Resveratrol, a natural compound, may be an alternative to improving conventional breast cancer therapy. Thus, we assessed the capability of resveratrol at a low dose to enhance the in vitro effect of conventional theray in estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2)-positive breast cancer cells. METHODS: Cell viability of breast cancer cells was measured with neutral red uptake assay. Apoptosis, autophagy, cell cycle progression and cell proliferation were detected through hypotonic fluorescent solution assay, formation of acidic vesicular organelles, flow cytometry, and bromodeoxyuridine assay, respectively. Western blotting was performed to study the expression of pro-apoptotic, anti-apoptotic and autophagic proteins, and estrogen receptors. RESULTS: Resveratrol combined with tamoxifen metabolites or trastuzumab reduced cell viability of ER- and HER2-positive breast cancer cells, respectively. This effect was mainly associated with induction of apoptosis due to a greater formation of hypodiploid nuclei, reduced protein expression of procaspase-7, Bcl-2, Bcl-xL, and PARP; and increased expression of cleaved PARP. Resveratrol decreased the expression of ERα and increased that of ERß, contributing to the reduced viability on breast cancer cells. Combined treatments induced autophagy, evidenced by increased levels of acidic vesicular organelles and degradation of p62/SQSTM1 protein. Nevertheless, on inhibiting autophagy with 3-methyladenine, cell viability was further reduced and apoptosis was induced, suggesting a pro-survival role of autophagy, impairing apoptosis. CONCLUSIONS: Resveratrol increasead the in vitro cytotoxic effect of conventional therapy in breast cancer cells. However, it was necessary to block resveratrol-induced autophagy to improve the therapeutic response.

Exploring the epigenetic profile of ID4 in breast cancer: bioinformatic insights into methylation patterns and chromatin accessibility dynamics.

PURPOSE: Inhibitor of differentiation 4 (ID4) is a dominant-negative regulator of basic helix-loop-helix (bHLH) transcription factors. The expression of ID4 is dysregulated in various breast cancer subtypes, indicating a potential role for ID4 in subtype-specific breast cancer development. This study aims to elucidate the epigenetic regulation of ID4 within breast cancer subtypes, with a particular focus on DNA methylation and chromatin accessibility. METHODS: Bioinformatic analyses were conducted to assess DNA methylation and chromatin accessibility in ID4 regulatory regions across breast cancer subtypes. Gene Set Enrichment Analysis (GSEA) was conducted to identify related gene sets. Transcription factor binding within ID4 enhancer and promoter regions was explored. In vitro experiments involved ER+ breast cancer cell lines treated with estradiol (E2) and Tamoxifen. RESULTS: Distinct epigenetic profiles of ID4 were observed, revealing increased methylation and reduced chromatin accessibility in luminal subtypes compared to the basal subtype. Gene Set Enrichment Analysis (GSEA) implicated estrogen-related pathways, suggesting a potential link between estrogen signaling and the regulation of ID4 expression. Transcription factor analysis identified ER and FOXA1 as regulators of ID4 enhancer regions. In vitro experiments confirmed the role of ER, demonstrating reduced ID4 expression and increased methylation with estradiol treatment. Conversely, Tamoxifen treatment increased ID4 expression, indicating the potential involvement of ER signaling through ERα in the epigenetic regulation of ID4 in breast cancer cells. CONCLUSION: This study shows the intricate epigenetic regulation of ID4 in breast cancer, highlighting subtype-specific differences in DNA methylation and chromatin accessibility.

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.

CYP2D6 genotyping and the clinical impact on outcomes in breast cancer tamoxifen-treated patients.

Aims: To report the distribution of allele frequencies of CYP2D6 gene and to evaluate their influence on the clinical outcomes of a group of breast cancer patients receiving adjuvant tamoxifen treatment from Uruguay. Patients & methods: 199 samples were genotyped through real-time polymerase chain reaction assays. Metabolization profiles were inferred from the genotypes. Correlations were evaluated using Pearson's χ2 test. Results: Phenotype frequencies were 0.65 normal (NM), 0.30 intermediate (IM) and 0.05 poor metabolizers (PM). Similar clinical outcomes between NM and (PM + IM) patient groups (odds ratio = 1.011, 95% CI = 0.2703-3.7826; p = 0.987) were found. Conclusion: CYP2D6 allele frequencies were analyzed for the first time in a cohort from Uruguay. Results did not support any impact of CYP2D6 gene polymorphisms on clinical outcomes.

Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.

OBJECTIVE: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. METHODS: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). RESULTS: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. CONCLUSION: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.

Repurposing miconazole and tamoxifen for the treatment of Mycobacterium abscessus complex infections through in silico chemogenomics approach.

Drug repositioning is an alternative to overcome the complexity of the drug discovery and approval procedures for the treatment of Mycobacterium abscessus Complex (MABSC) infections that are increasing globally due to the emergency of antimicrobial resistance mechanisms. Here, an in silico chemogenomics approach was performed to compare the sequences from 4942 M. abscessus subsp. abscessus (M. abscessus) proteins with 5258 or 3473 therapeutic targets registered in the DrugBank or Therapeutic Target Database, respectively. This comparison identified 446 drugs or drug candidates whose targets were homologous to M. abscessus proteins. These identified drugs were considered potential inhibitors of MABSC (anti-MABSC activity). Further screening and inspection resulted in the selection of ezetimibe, furosemide, itraconazole, miconazole (MCZ), tamoxifen (TAM), and thiabendazole (THI) for experimental validation. Among them, MCZ and TAM showed minimum inhibitory concentrations (MIC) of 32 and 24 µg mL-1 against M. abscessus, respectively. For M. bolletii and M. massiliense strains, MCZ and TAM showed MICs of 16 and 24 µg mL-1, in this order. Subsequently, the antibacterial activity of MCZ was confirmed in vivo, indicating its potential to reduce the bacterial load in the lungs of infected mice. These results show that MCZ and TAM can serve as molecular scaffolds for the prospective hit-2-lead optimization of new analogs with greater potency, selectivity, and permeability.

Tamoxifen as a modulator of CXCL12-CXCR4-CXCR7 chemokine axis: A breast cancer and glioblastoma view.

The chemokine stromal cell-derived-factor 1 (SDF)-1/CXCL12 acts by binding to its receptors, the CXC-4 chemokine receptor (CXCR4) and the CXC-7 chemokine receptor (CXCR7). The binding of CXCL12 to its receptors results in downstream signaling that leads to cell survival, proliferation and migration of tumor cells. CXCL12 and CXCR4 are highly expressed in breast cancer (BC) and glioblastoma (GBM) compared to normal cells. High expression of this chemokine axis correlates with increased therapy resistance and grade, tumor spread and poorer prognosis in these tumors. Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) that inhibits the expression of estrogen-regulated genes, including growth and angiogenic factors secreted by tumor cells. Additionally, TMX targets several proteins, such as protein kinase C (PKC), phospholipase C (PLC), P-glycoprotein (PgP), phosphatidylinositol-3-kinase (PI3K) and ion channels. This drug showed promising antitumor activity against both BC and GBM cells. In this review, we discuss the role of the CXCL12-CXCR4-CXCR7 chemokine axis in BC and GBM tumor biology and propose TMX as a potential modulator of this axis in these tumors. TMX modulates the CXCL12-CXCR4-CXCR7 axis in BC, however, there are no studies on this in GBM. We propose that studying this axis in GBM cells/patients treated with TMX might be beneficial for these patients. TMX inhibits important signaling pathways in these tumors and the activation of this chemokine axis is associated with increased therapy resistance.

Tamoxifen associated to the conservative CKD treatment promoted additional antifibrotic effects on experimental hypertensive nephrosclerosis.

CKD progression depends on the activation of an intricate set of hemodynamic and inflammatory mechanisms, promoting renal leukocyte infiltration, inflammation and fibrosis, leading to renal function loss. There are currently no specific drugs to detain renal fibrogenesis, which is a common end-point for different nephropathies. Clinical therapy for CKD is mostly based on the management of hypertension and proteinuria, partially achieved with renin-angiotensin-aldosterone system (RAAS) blockers, and the control of inflammation by immunosuppressive drugs. The aim of the present study was to verify if the administration of tamoxifen (TAM), an estrogen receptor modulator, clinically employed in the treatment of breast cancer and predicted to exert antifibrotic effects, would promote additional benefits when associated to a currently used therapeutic scheme for the conservative management of experimental CKD. Wistar rats underwent the NAME model of hypertensive nephrosclerosis, obtained by daily oral administration of a nitric oxide synthesis inhibitor, associated to dietary sodium overload. The therapeutic association of TAM to losartan (LOS), and mofetil mycophenolate (MMF) effectively reduced the severe hypertension, marked albuminuria and glomerular damage exhibited by NAME animals. Moreover, the association also succeeded in limiting renal inflammation in this model, and promoted further reduction of ECM interstitial accumulation and renal fibrosis, compared to the monotherapies. According to our results, the association of TAM to the currently used conservative treatment of CKD added significant antifibrotic effects both in vivo and in vitro, and may represent an alternative to slow the progression of chronic nephropathy.

Subchronic exposure to Tamoxifen modulates the hippocampal BDNF/ERK/Akt/CREB pathway and impairs memory in intact female rats.

Tamoxifen (TAM), a Selective Estrogen Receptor Modulator (SERM), is commonly used to treat and prevent breast cancer. Memory impairment has been noticed in patients who experience hormone therapy in the case of TAM and other SERMs. Animal studies that mimic the TAM longer exposure effects are needed to better elucidate the adverse effects of continuous treatment in humans. This study evaluated the effects of TAM subchronic administration on the memory performance and hippocampal neural plasticity of intact female Wistar rats. Animals were treated intragastrically with TAM (0.25 and 2.5 mg/kg) for 59 days. The rats were subjected to the Object Location Test (OLT) and Object Recognition Test (ORT) to evaluate memory performance. After euthanasia, the hippocampus samples were excised and the protein levels of the BDNF/ERK/Akt/CREB pathway were evaluated. The rat's locomotor activity and hippocampal TrkB levels were similar among the experimental groups. TAM at both doses reduced the memory performance of female rats in the OLT and short-term memory of ORT, and impaired hippocampal levels of mBDNF, proBDNF, and pCREB/CREB. TAM only at the dose of 2.5 mg/kg reduced the memory performance of rats in the long-term memory of ORT and hippocampal pERK/ERK and pAkt/Akt ratios. TAM subchronic administration induced amnesic effects and modulated the hippocampal BDNF/ERK/Akt/CREB pathway in intact young adult female Wistar rats.

Projected Savings for Generic Oncology Drugs Purchased via Mark Cuban Cost Plus Drug Company Versus in Medicare.

PURPOSE: Self-administered oncology drugs contribute disproportionately to Medicare Part D spending; prices often remain high even after generic entry. Outlets for low-cost drugs such as Mark Cuban Cost Plus Drug Company (MCCPDC) offer opportunities for decreased Medicare, Part D, and beneficiary spending. We estimate potential savings if Part D plans obtained prices such as those offered under the MCCPDC for seven generic oncology drugs. METHODS: Using the 2020 Medicare Part D Spending dashboard, Q3-2022 Part D formulary prices, and Q3-2022 MCCPDC prices for seven self-administered generic oncology drugs, we estimated Medicare savings by replacing Q3-2022 Part D unit costs with costs under the MCCPDC plan. RESULTS: We estimate potential savings of $661.8 million (M) US dollars (USD; 78.8%) for the seven oncology drugs studied. Total savings ranged from $228.1M USD (56.1%) to $2,154.5M USD (92.4%) compared with 25th and 75th percentiles of Part D plan unit prices. The median savings replacing Part D plan prices were abiraterone $338.0M USD, anastrozole $1.2M USD, imatinib 100 mg $15.6M USD, imatinib 400 mg $212.0M USD, letrozole $1.9M USD, methotrexate $26.7M USD, raloxifene $63.8M USD, and tamoxifen $2.6M USD. All 30-day prescription drug prices offered by MCCPDC generated cost savings except for three drugs offered at the 25th percentile Part D formulary pricing: anastrozole, letrozole, and tamoxifen. CONCLUSION: Replacing current Part D median formulary prices with MCCPDC pricing could yield significant savings for seven generic oncology drugs. Individual beneficiaries could save nearly $25,200 USD per year for abiraterone or between $17,500 USD and $20,500 USD for imatinib. Notably, Part D cash-pay prices for abiraterone and imatinib under the catastrophic phase of coverage were still more expensive than baseline MCCPDC prices.

Evaluation of a polymeric topical formulation of Endoxifen in an estrogen receptor positive breast cancer murine model.

Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease.

Health-related quality of life of women with breast cancer being treated with hormone therapy: A scoping review.

OBJECTIVE: To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy. DATA SOURCES: This review followed the Joanna Briggs Institute methodological recommendations and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. Searches were performed in nine databases using descriptors, synonyms and keywords; grey literature was also included. The review protocol was registered with the Open Science Framework under doi: http://doi.org/10.17605/OSF.IO/347FM. Inclusion criteria were established according to the Population, Concept, and Context strategy. The selection of studies was performed by two independent reviewers with the aid of RAYYAN software and disagreements were resolved by a third reviewer. The main information from the included articles was grouped into textual categories and presented by means of a narrative synthesis. DATA SUMMARY: A total of 5419 records were identified, of which 42 studies fully met the eligibility criteria. Most were multicenter studies (42.9%) and randomized controlled trials (62%). Most studies addressed anastrozole (39.5%), letrozole (34.2%), and tamoxifen (26.3%), which were studied alone or in combination. The most widely used health-related quality-of-life assessment tool was the EORTC-QLQ-C30. The concomitant use of hormone therapy and cyclin-dependent kinase inhibitors 4 and 6 showed improvement in health-related quality of life. CONCLUSION: In recent years there has been an increase in studies focused on health-related quality of life, and the evidence pointed to relevant information on health-related quality of life and the use of endocrine therapy, tamoxifen in combination with aromatase inhibitors, as well as aromatase inhibitor alone and the use of cyclin-dependent kinase 4 and 6.

Risk factors for the development of endometrial lesions in breast cancer patients using tamoxyphen: a retrospective cohort study.

INTRODUCTION: breast cancer is the cancer with the highest incidence in women in Brazil, representing 29.7% of all cancers. More than two thirds of women with breast cancer show expression for hormone receptors, and in these cases, hormone therapy with tamoxifen is indicated, which may represent a risk factor for the development of endometrial cancer (four-fold greater relative risk). OBJECTIVE: this study aimed to evaluate the association of tamoxifen and the development of endometrial disturbances and to assess possible other associated risk factors. PATIENTS AND METHOD: a total of 364 breast cancer patients were evaluated, 286 who used tamoxifen and 78 who did not use this hormone therapy. Results: patients who used tamoxifen had a mean follow-up time of 51.42 months similar to those without hormone therapy (p=0.081). A total of 21 (7.3%) women who used tamofixen and no cases among women without hormone therapy presented endometrial changes during follow-up (p=0.01). Despite information regarding obesity was available for only 270 women, obesity was also significantly associated with the development of endometrial changes (p=0.008). CONCLUSION: furthermore, the association between tamofixen and endometrial changes remained significant (p=0.039) after adjusting for obesity.

Comparison of tamoxifen and hormone replacement cycle (HRT) in frozen embryo transfer. A randomized controlled trial.

OBJECTIVE: The use of frozen embryos in the treatment of infertility with assisted reproductive techniques has been increased. Different methods are used to prepare the endometrium for frozen embryo transfer (FET). The aim of this study was to compare pregnancy outcomes after treatment with tamoxifen and hormonal replacement therapy (HRT) in FET. METHODS: This randomized clinical trial was carried out with 214 infertile women in the infertility research center of Milad Hospital in Mashhad during 2018-2020. We had 84 patients receiving tamoxifen and 92 took HRT. Endometrial thickness (ET) and pregnancy outcome were measured in both groups. RESULTS: Mean infertility duration (p=0.328), number of embryos (p=0.649), FSH (p=0.390), LH (p=0.051) and LH/FSH ratio (p=0.287) as well as type of infertility (primary or secondary) (p=0.295), causes of infertility (p=0.750) and pattern of menstruation (p=0.676) were not significantly different in the two groups. Mean ET in the TMX and HRT groups were 8.72±1.45mm and 9.00±1.69mm, respectively (p=0.423). There was no statistically significant difference between chemical pregnancy (p=0.663), clinical pregnancy (p=0.994) and ongoing pregnancy (p≥0.999) in the TMX and HRT groups. CONCLUSIONS: Treatment with tamoxifen can be as effective as GnRH agonist for endometrial preparation in FET.

Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen.

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.

Borderline indications for ovarian suppression: addressing uncertainties with patients.

Ovarian function suppression (OFS) is a potentially life-saving treatment for young women diagnosed with high-risk hormonal-receptor (HR)+ early breast cancer (EBC), albeit one associated with significant side effects that may adversely affect quality of life. Of particular concern, this article raises a few borderline indications that were largely unaddressed in pivotal clinical trials but are still commonly encountered in daily practice. These, referred to here as 'borderline indications of OFS' remain a source of uncertainty for patients and physicians and are concisely addressed in this article.

This article is about a treatment for breast cancer that is a type of drug-induced menopause. It is considered highly effective for young women diagnosed with a specific form of breast cancer. However, it often causes significant side effects. The author addresses several situations, commonly encountered in daily medical practice, in which the indication for this treatment is controversial.

Effects of Cimicifuga racemosa (L.) Nutt on sexual function in women receiving tamoxifen for breast cancer.

To assess the effects of Cimicifuga racemosa (L.) Nutt on climacteric symptoms and sexual function in women receiving tamoxifen after breast cancer treatment. A prospective study of women treated at the Mastology Outpatient Clinic of the Department of Obstetrics and Gynecology of the Santa Casa de Sao Paulo School of Medical Science of the hospital was conducted between 2018 and 2021. Patients diagnosed with breast cancer that underwent surgical, radiotherapy and chemotherapy treatment more than one year prior, receiving tamoxifen, exhibited climacteric symptoms and were sexually active were selected. Total of 34 women were recruited and during outpatient visits completed sociodemographic questionnaire, Blatt-Kupperman Index (KI) and Female Sexual Function Index (FSFI). The group showed improvements in climacteric symptoms (p<.001) and sexual function (p=.011) after the 6-month follow-up. Cimicifuga racemosa (L.) Nutt promoted improvements in climacteric symptoms and sexual function in women surgically treated for breast cancer. Clinical Trials.gov ID: NCT02467686.Impact StatementWhat is already known on this subject? The medications used for the treatment of breast cancer can lead to important complaints of vasomotor manifestations with a negative impact on the success of their treatment, and cases have been described until their interruption. Cimicifuga racemosa (L.) Nutt. is described in several works as a therapy to alleviate these symptoms. Numerous works in the literature present climatic symptoms and sexual function with a selective approach to the themes.What do the results of this study add? Our study evaluated a group of women who were treated for breast cancer after menopause taking into account the following aspects: climacteric symptoms and sexual function. When we reviewed the literature, we did not find, so far, work similar to ours.What are the implications of these findings for clinical practice and/or further research? In clinical practice, assessing vasomotor symptoms and sexual response of breast cancer patients can contribute towards improving the lives of this patient group. Prescribing Cimicifuga racemosa (L.) Nutt in cases with climacteric complaints and poor sexual response can relieve distress and promote better health and life status for these women. Although the present investigation has generated important data on female breast cancer survivors, there are limitations regarding the number of participants. We recommend further clinical research with expansion of the sample studied and the results presented.

Predictores histopatológicos de respuesta a tratamiento en pacientes con cáncer de mama receptores hormonales positivos her2 negativo. Un estudio de centro único / Histopathological predictors of response to treat-ment in patients with hormone receptor positive her2 negative breast cancer. A single center study

In troducción: Una de cada 18 mujeres desarrolla a lo largo de su vida cáncer de mama, siendo esta la principal causa de muerte por cáncer en mujeres.El propósito del presente estudio fue establecer el valor predictivo de los factores histopatológicos presentes en tumores malignos de mama con recepto-res hormonales positivos Her2 negativo de un grupo de pacientes en un centro de referencia oncológico.Met odología: Este estudio longitudinal se realizó en el Instituto Oncológico Nacional "Dr Juan TancaMa-rengo", de Guayaquil -Ecuador. El período de inclusión del 2007 al 2009 con período de observación hasta diciembre del 2020. Con una muestra no probabilística, se incluyeron mujeres con cáncer de mama, hormonal positivo Her2Neu negativo, que hayan recibido tratamiento adyuvante durante un pe-riodo de seguimiento. Se midieron variables demográficas, clínicas, relacionadas al tumor, clasificación TNM y sobrevida.Se realiza un análisis univariado descriptivo de la muestra, un análisis bivariado, com-parando el grupo de pacientes fallecidas con el grupo de pacientes vivas; un análisis de correlación entre variables en escala; un análisis de supervivencia y finalmente se presenta una regresión COX para pre-decir la supervivencia en base a las variables.R esultados: Ingresaron al estudio 105 pacientes, de 54.1 ± 11.4 años. 58.1% de casos en etapa temprana y 41.9% en etapa localmente avanzada. La sobrevida global (SG) fue de 67.6%a 14 añosy la sobrevida librede progresión (SLP) del 59.05%. La terapia de bloqueo hormonal se asoció con la SLP (R=0.544, P<0.01) y con SG (R=0.399, P<0.05). El compromiso ganglionar en estadio N0 tuvo una SLP de 11.9 ± 0.4 años, en estadio N3 fue de 6.8 ± 1.6 años (P<0.01). El modelo de regresión de Cox para predecir el tiempo de vida libre de progresión o enfermedad fue estadísticamente significativo con la terapia de bloqueo hormonal (R2=0.607, P<0.001) Conclusión: Laterapia de bloqueo hormonal mantenida por más de 5 años tiene un impacto positivo en la supervivencia de las pacientes con cáncer de mama hormonal positivo Her2 Neu negativo

In troduction:One in 18 women develops breast cancer throughout her life, this being the leading cause of death from cancer in women. The purpose of the present study was to establish the predictive value of the histopathological factors present in malignant breast tumors with positive hormone receptors Her2 negative in a group of patients in an oncology reference center.Met hodology: This longitudinal study was conducted at the "Dr. Juan Tanca Marengo" National Oncology Institute in Guayaquil -Ecuador. The inclusion period was from 2007 to 2009, with an observation period until December 2020. With a non-probabilistic sample, women with hormone-positive Her2 Neu negative breast cancer who had received adjuvant treatment during a follow-up period were included. Demo-graphic, clinical, tumor-related, TNM classification and survival variables were measured. A descriptive univariate analysis of the sample is performed, a bivariate analysis comparing the group of deceased patients with the group of living patients; a correlation analysis between variables in scale; a survival analysis; and a COX regression is presented to predict survival based on the variables.R esults: 105 patients,54.1 ± 11.4 years old, entered the study. 58.1% of cases are in the early stage, and 41.9% are in a locally advanced stage. Overall survival (OS) was 67.6% at 14 years, and progression-free survival (PFS) was 59.05%. Hormone blocking therapy was associated with PFS (R=0.544, P<0.01) and OS (R=0.399, P<0.05). Lymph node involvement in stage N0 had a PFS of 11.9 ± 0.4 years; stage N3 was 6.8 ± 1.6 years (P<0.01). The Cox regression model to predict progression-free or disease-free life was statistically significant with hormone blockade therapy (R2=0.607, P<0.001).C o nclusion: Hormone blockade therapy maintained for more than five years positively impacts the sur-vival of patients with hormone-positive Her2 Neu negative breast cancer.

Tamoxifen improves homeostasis in the peri-implant bone remodeling of osseointegrated titanium implants.

BACKGROUND: The purpose of this preclinical study was to evaluate the influence of tamoxifen (TAM) on the peri-implant bone remodeling of osseointegrated titanium implants in ovariectomized female rats. MATERIALS AND METHODS: Seventy-two female rats underwent bilateral ovariectomy 20 weeks before implants placement. One titanium implant was inserted in each tibia of the animals. Six weeks following the implant surgery, animals were randomly divided into two experimental groups (n = 36), which received either saline solution (SS) or tamoxifen citrate (TAM) via gavage until euthanasia. Euthanasia was performed at 30, 60, and 90 days after the first gavage. Assessments of bone to implant contact (BIC), bone ingrowth percentage (BIN), morphological description of cellular and tissue reactions, immunohistochemistry for the detection of bone morphogenetic protein 2/4 (BMP2/4), runt-related transcription factor 2 (RUNX-2), osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP), and bone chemical composition through scanning electron microscopy with energy-dispersive x-ray spectroscopy were performed. RESULTS: Tamoxifen group presented higher BIC, higher BIN, higher RUNX-2 and OCN, lower TRAP-positive cells/mm2 , and no differences regarding BMP-2/4 positive cells/mm2 than SS group in all periods. TAM group also showed higher Ca/P rate than SS group. CONCLUSION: Tamoxifen enhanced the remodeling of the bone surrounding titanium implants in ovariectomized rats.