Triple combination of palliative oral metronomic chemotherapy in recurrent and metastatic epithelial ovarian cancer: A retrospective study

Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post?treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan?Meier analyses were performed. Progression?free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35?80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group?Performance Status (ECOG?PS) was 0�in 28 patients and 2�in 12 patients. The best clinical response rate post?oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow?up was 6.4 months (4.5�2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade?I/II mucositis. Grade?III/IV mucositis were observed in 9 (22.5%) patients. Thirty?seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well?tolerated regime with good symptomatic control and low?moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade?III/IV thrombocytopenia.

Research Progress in the Role of Tamoxifen in Nervous System and Cognitive Function / 中国医学科学院学报

Neurological diseases include a variety of neurodegenerative diseases and other brain damage diseases.The treatment schemes for neurological diseases are still in research.The existing clinical and basic studies have confirmed that traditional estrogen therapy has certain protective effect on the nervous system,while it increases the risk of breast or endometrial cancer.The emergence of the selective estrogen receptor modulators (SERMs) can avoid the above mentioned problems.The available studies have confirmed the protective effect of tamoxifen as a SERM on the nervous system.This paper reviews the role and functioning mechanisms of tamoxifen in the nervous system and cognitive function,aiming to provide guidance for the future application of tamoxifen in the treatment of neurological diseases and the improvement of cognitive function.

Risk factors for the development of endometrial lesions in breast cancer patients using tamoxyphen: a retrospective cohort study / Estudo de coorte retrospectivo para avaliação de fatores de risco para desenvolvimento de lesão endometrial em pacientes com câncer da mama em uso de tamoxifeno

ABSTRACT 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.

RESUMO Introdução: o câncer da mama é o câncer de maior incidência no sexo feminino no Brasil, representando 29,7% de todos os cânceres. Mais de dois terços das mulheres com câncer da mama apresentam expressão para receptores hormonais, estando, nestes casos, indicada a terapia hormonal com tamoxifeno, que pode representar fator de risco para o desenvolvimento do câncer do endométrio (risco relativo quatro vezes maior). Objetivo: este trabalho teve como objetivo avaliar a associação entre o uso de tamoxifeno e o desenvolvimento de distúrbios endometriais bem como eventuais outros fatores associados. Pacientes e método: Estudo de coorte retrospectivo de 364 pacientes com câncer da mama, das quais 286 utilizaram tamoxifeno e 78 não utilizaram esta hormonioterapia. Resultados: pacientes que usaram tamoxifeno tiveram um seguimento médio de 51,42 meses, semelhante àquelas sem terapia hormonal (p=0,081). Um total de 21 (7,3%) mulheres que usaram tamofixeno e nenhuma mulher sem terapia hormonal apresentaram alterações endometriais durante o seguimento (p=0,01). Nas 270 mulheres que tinham informação sobre obesidade, esta se associou significantemente com o desenvolvimento de alterações endometriais (p=0,008). A associação entre tamofixeno e alterações endometriais permaneceu significante (p=0,039) após ajustar para interação com obesidade. Conclusão: o uso de tamoxifeno no tratamento do câncer da mama esteve associado ao maior risco para desenvolvimento de alterações endometriais especialmente quando associado à obesidade.

Effects of Qingruxiao granules combined with tamoxifen on mammary hyperplasia and its effects on serum hypoxia inducible factor-1α, angiopoietin-2 and prolactin levels / 中国基层医药

Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.

Encapsulating peritoneal sclerosis: from early diagnosis to successful kidney transplantation / Esclerose peritoneal encapsulante: do diagnóstico precoce ao transplante renal bem-sucedido

Abstract Encapsulating peritoneal sclerosis is an uncommon but serious complication of peritoneal dialysis. In most cases, the symptoms appear after peritoneal dialysis withdrawal, which hampers its diagnosis. We present the case of a 44-years-old Caucasian male who had been on peritoneal dialysis for 6 years and 3 months and was switched to hemodialysis due to ultrafiltration failure. During his last months on peritoneal dialysis, he developed anorexia and asthenia, which were initially attributed to dialysis inadequacy. After hemodialysis induction, the patient developed abdominal pain, increased abdominal volume, obstipation alternating with diarrhea, and weight loss. Computed tomography showed de novo ascites. A diagnosis of early encapsulating peritoneal sclerosis was considered, and treatment was promptly initiated with nutritional support, oral prednisolone, and tamoxifen for one year. The patient progressed with resolution of the symptoms. One month after the end of the treatment, he underwent a successful kidney transplant and remain without any major intercurrences. A high level of clinical suspicion is crucial for the early diagnosis of encapsulating peritoneal sclerosis as the disease can be fatal in advanced stages. This case highlights that with early treatment, kidney transplantation can be successfully performed after an episode of encapsulating peritoneal sclerosis.

Resumo A esclerose peritoneal encapsulante é uma complicação incomum, mas grave, da diálise peritoneal. Na maioria dos casos, os sintomas aparecem após a suspensão da diálise peritoneal, o que dificulta seu diagnóstico. Apresentamos o caso de um homem caucasiano de 44 anos de idade que esteve em diálise peritoneal por 6 anos e 3 meses e foi transferido para hemodiálise devido a falha de ultrafiltração. Durante seus últimos meses em diálise peritoneal, ele desenvolveu anorexia e astenia, que foram inicialmente atribuídas à inadequação da diálise. Após a indução de hemodiálise, o paciente desenvolveu dor abdominal, aumento do volume abdominal, obstipação alternada com diarreia, e perda de peso. A tomografia computadorizada mostrou ascite de novo. Foi considerado um diagnóstico de esclerose peritoneal encapsulante precoce, e o tratamento foi prontamente iniciado com suporte nutricional, prednisolona oral e tamoxifeno por um ano. O paciente progrediu com resolução dos sintomas. Um mês após o término do tratamento, ele foi submetido a um transplante renal bem-sucedido e permanece sem maiores intercorrências. Um alto nível de suspeita clínica é crucial para o diagnóstico precoce da esclerose peritoneal encapsulante, uma vez que a doença pode ser fatal em estágios avançados. Este caso destaca que, com tratamento precoce, o transplante renal pode ser realizado com sucesso após um episódio de esclerose peritoneal encapsulante.

Fatores de risco correlacionados à alopecia frontal fibrosante em Criciúma, Santa Catarina: estudo caso-controle / Risk factors correlated with frontal fibrosing alopecia in Criciuma, Santa Catarina: case-control study

Introdução: A alopecia frontal fibrosante (AFF) é uma forma de alopecia cicatricial, em que os pacientes apresentam perda irreversível dos folículos pilosos, principalmente em região frontal e tempoparietal. Sua etiopatogenia não está totalmente elucidada, embora hipóteses sobre fatores genéticos, hormonais e comportamentais, como o uso de filtro solar e hidratante facial, já tenham sido descritas. Métodos: estudo de caso-controle, realizado com aplicação de um questionário objetivo com 33 perguntas. Foram avaliadas 60 pacientes do sexo feminino, 30 diagnosticadas com AFF e 30 não acometidas pela doença. Resultados: a média de idade da amostra foi de 64 anos (± 10,37 para casos e ± 9,40 para os controles). 76,7% das pacientes com AFF e 23,3% dos controles faziam uso de filtro solar, sendo a diferença estatisticamente significativa (p<0,001). Além disso, o uso de hidratante facial mostrou-se significativamente maior nas pacientes com alopecia (63,3%) quando comparadas aos controles (33,3%; p=0,038). Notou-se a frequência de uso de sabonete comum na face significativamente menor nas pacientes com AFF (46,7%), quando comparada ao grupo controle (83,3%; p=0,006). Conclusão: nossos resultados sugerem uma possível associação entre AFF e uso de produtos faciais, como filtro solar e hidratante. Todas as pacientes eram menopausadas, reforçando a relação hormonal com a doença

Introduction: Fibrosing Frontal Alopecia (FFA) is a form of scarring alopecia, in which patients have an irreversible loss of hair follicles, especially in the frontal and temporoparietal regions. The etiopathogenesis is not fully understood, although hypotheses about genetic, hormonal, and behavioral factors, such as the use of sunscreen and facial moisturizers, have already been described. Methods: A case-control study was conducted using an objective questionnaire with 33 questions. Sixty women were evaluated, 30 diagnosed with FFA, and 30 not affected by the disease. Results: The mean age of the sample was 64 years old. 76.7% of patients with FFA and 23.3% of controls used facial sunscreen and the difference was statistically significant (p<0.001). Also, the use of facial moisturizer was significantly higher in patients with alopecia (63.3%) when compared to controls (33.3%; p=0.038). The frequency of use of regular soap on the face was significantly lower in patients with FFA (46.7%) when compared to the control group (83.3%; p=0.006). Conclusion: Results suggest a possible association between FFA and the use of facial products, such as sunscreen and moisturizer, in this population. All patients were menopausal, reinforcing the hormonal relationship with the disease.

The mechanism by which tamoxifen attenuates high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells / 中国基层医药

Objective:To investigate the effects of tamoxifen on high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells and the underlying mechanism.Methods:The peritoneal mesothelial cells of normal male SD rats were selected between January 2015 and June 2016 and then cultured and divided into blank control, high-glucose stimulation and drug intervention groups. High-glucose stimulation group: primary cultured rat peritoneal mesothelial cells (RPMCs) were treated with 60 mmol/L high-concentration glucose to induce epithelial-to-mesenchymal transition. Drug intervention group: (1) RPMCs were treated with 60 mmol/L high-concentration glucose and different concentrations (0.5 μmol/L, 2 μmol/L) of tamoxifen. After 72 hours of stimulation, protein was extracted. (2) RPMCs were treated with 60 mmol/L high-concentration glucose and 2 μmol/L tamoxifen with or without 2 μmol/L ER-α antagonist for 1 hour to extract protein and for 6 hours to extract RNA. (3) RPMCs were treated with high-concentration glucose and 2 μmol/L tamoxifen with or without 1 μmol/L 1 μM proteasome inhibitor for 1 hour to extract protein. Western blot analysis was performed to analyze change in E-cadherin, α-SMA, Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 protein. Real-time fluorescence quantitative PCR was performed to detect the change in mRNA expression of Smad2, Smad3, connective tissue growth factor and plasminogen activator inhibitor 1.Results:Tamoxifen attenuated epithelial-to-mesenchymal transition on RPMCs induced by high-level glucose, showing increased expression of epithelial cell marker E-cadherin and decreased expression of α-SMA in a concentration-dependent manner ( tE-cadherin = 2.31, tα-SMA =-2.53, both P < 0.05).TGF-β1/R-Smad signal pathway was activated by high-concentration glucose. Phosphorylation of Smad2/3 and mRNA expression of CTGF and PAI-1 were increased. Tamoxifen remarkably reduced protein and mRNA level of above mentioned protein and related target genes ( tp-Smad2 = -3.38, tCTGF = -3.81, P < 0.05), which could be blocked by ER-α antagonist. Finally, proteasome inhibitor could weaken the inhibitory effects of tamoxifen on p-Smad2/3 and increase p-Smad2/3 protein level ( tp-Smad2 = 3.94, P < 0.05). Conclusion:Tamoxifen activates ER-α on RPMCs, weakens the activation of TGF-β1/R-Smad signal pathway through decreasing p-Smad2 protein level, and effectively inhibits the progression of high-concentration glucose-induced epithelial-to-mesenchymal transition possibly through degrading p-Smad2 protein through proteasome. The role of tamoxifen in epithelial-to-mesenchymal transition may provide a possible guide for research, prevention and treatment of peritoneal fibrosis.

Inhibitory effects and mechanisms of cryptotanshinone on the growth of tamoxifen resistant breast cancer cells / 药学学报

This study investigated the inhibitory effect and mechanisms of cryptotanshinone (CPT) on tamoxifen resistant cell MCF7-TAMR. The inhibitory effect of CPT on the viability of MCF7-TAMR cells was evaluated using the MTT assay. We found that CPT significantly inhibited the growth of MCF7-TAMR cells in a dose- and time-dependent manner. The half inhibitory concentration (IC50) is 15.14 ± 2.82 μmol·L-1 at 24 h. CPT induced cell cycle arrest of MCF7-TAMR cells at G0/G1 phase, and promoted apoptosis of MCF7-TAMR cells by upregulating intracellular levels of reactive oxygen species (ROS). Transwell results showed that CPT significantly inhibited the migration of MCF7-TAMR cells. Furthermore, CPT decreased the CD24-/lowCD44+ cell population in MCF7-TAMR cell-derived microspheres. Western blot results showed that CPT effectively inhibited the phosphorylation of estrogen receptor α (ER-α), and reduced the expression of phosphatidylinositol 3-kinase (PI3K-p85), serine-threonine protein kinase (Akt) and multidrug transporter ATP-binding cassette superfamily G member 2 (ABCG2). These results showed that CPT can induce cell apoptosis, cause cell cycle arrest, inhibit cell migration and inhibit ER-α phosphorylation, inhibit PI3K/Akt signaling pathway, reduce the number of CD24-/lowCD44+ cells and the expression of ABCG2, overcome cell drug resistance.

Multimodal imaging features of tamoxifen retinopathy / 中华眼底病杂志

Objective:To observe the multimodal imaging characteristics of tamoxifen retinopathy.Methods:A retrospective case study. From January 2019 to December 2021, 4 patients (8 eyes) with tamoxifen retinopathy diagnosed in Tangshan Eye Hospital were included in the study. All patients were female, with sick binoculus. The age was 59.5±4.6 years. After breast cancer resection, tamoxifen 20 mg/d was taken orally consecutively, including 1, 1, and 2 cases who took tamoxifen orally for 5, 7, and ≥10 years. All eyes were examined by fundus color photography, optical coherence tomography (OCT), OCT angiography (OCTA), fundus fluorescein angiography (FFA), and fundus autofluorescence (AF). The multi-mode image features of the fundus of the affected eyes were observed.Results:The yellow white dot crystal like material deposition in the macular area was observed in all eyes. In fundus AF examination, macular area showed patchy strong AF. FFA examination showed telangiectasia and fluorescein leakage in macular area at late stage. OCT showed that punctate strong reflexes could be seen between the neuroepithelial layers in the macular region with the formation of a space between the neuroepithelial layers, the interruption of the elliptical zone (EZ), and the formation of a hole in the outer lamella including 4, 5 and 3 eyes; The thickness of ganglion cells in macular region decreased in 7 eyes. OCTA showed that the blood flow density of the superficial retinal capillary plexus around the arch ring was decreased, and the retinal venules were dilated in 2 eyes; Deep capillary plexus (DCP) showed telangiectasia.Conclusion:Deposition of yellowish white dot like crystals can be seen in the macular region of tamoxifen retinopathy; dotted strong reflex between neuroepithelial layers, cavity formation, thinning of ganglion cell layer, EZ middle fissure and outer lamellar fissure; DCP capillaries and venules around the arch were dilated; telangiectasia in macular region; flaky strong AF in macular region.

Hiperplasia endometrial asociada al uso del tamoxifeno en pacientes con cáncer de mama en Barranquilla / Endometrial hyperplasia associated with use of tamoxifen in patients with breast cancer in Barranquilla

Resumen Introducción: el tamoxifeno ha sido el medicamento de primera línea para el tratamiento del cáncer de mama; sin embargo, se han evidenciado serios eventos adversos con su uso. El objetivo de este trabajo fue determinar la hiperplasia endometrial asociada al uso de tamoxifeno en mujeres con cáncer de mama en una institución oncológica de la ciudad de Barranquilla- Colombia. Metodología: estudio de casos y controles retrospectivo. Se incluyeron 202 pacientes con cáncer de mamá tratadas entre 2012 y 2017. Fueron evaluadas variables antropométricas, sociodemográficas, personales, clínicas y patológicas. Se estimaron los Odds Ratios (OR) crudos y ajustados. Resultados: 68 participantes fueron diagnosticadas con hiperplasia endometrial secundaria al tratamiento antineoplásico. De éstas, 59 (86,7 %) usaron tamoxifeno, la mayoría (37,2 %) por un lapso de 6-11 meses. El análisis bivariado mostró asociación entre la hiperplasia endometrial y uso del tamoxifeno con un OR de 3,9 (IC95 %: 1,8-8,5) y 2,9 (IC95 %: 1,18-7,5) en los análisis crudos y ajustados, respectivamente. Conclusión: el uso de tamoxifeno se asocia con la presencia de hiperplasia endometrial.

Abstract Introduction: tamoxifen has been the first line drug for the treatment of breast cancer; however, serious adverse events have been evidenced with its use. The aim of this study was to determine endometrial hyperplasia associated with the use of tamoxifen in women with breast cancer in an oncological institution in the city of Barranquilla, Colombia. Methodology: retrospective case-control study. A total of 202 patients with breast cancer treated between 2012 and 2017 were included. Anthropometric, sociodemographic, personal, clinical and pathological variables were evaluated. Crude and adjusted Odds ratios (OR) were estimated. Results: 68 participants were diagnosed with endometrial hyperplasia secondary to antineoplastic treatment. Of these, 59 (86.7 %) used tamoxifen, the most of them (37.2 %) for a period of 6-11 months. Bivariate analysis showed an association between endometrial hyperplasia and tamoxifen use with an OR of 3.9 (95%CI: 1.8-8.5) and 2.9 (95%CI: 1.18-7.5) in the crude and adjusted analyses, respectively. Conclusion: tamoxifen use is associated with the presence of endometrial hyperplasia.

Ginecomastia: Consideraciones médicas y quirúrgicas en cirugía general / Gynecomastia: Medical and surgical considerations in general surgery

La ginecomastia, definida como el crecimiento del tejido glandular mamario en los hombres, aparece desde la etapa neonatal hasta la senil, puede ser unilateral o bilateral, y es de causa multifactorial, incluyendo aquellos pacientes asociados al uso de medicamentos, donde predomina un desbalance en la relación testosterona­estrógeno. Relativamente, la idiopática es la más frecuente. La mayoría involucionan espontáneamente, las neonatales por perdida del influjo transplacentario en las primeras semanas, y las puberales entre 12 a 24 meses. Se presenta como un aumento del tamaño mamario, asintomático o con hipersensibilidad por inflamación durante el crecimiento del tejido fibroglandular mamario, con una repercusión psicológica enorme, sobre todo en la etapa de la adolescencia. El estudio y manejo es interdisciplinario y se ofrece de acuerdo con las condiciones y la etiología. Aquellos pacientes púberes en quienes no involuciona reciben tratamientos médicos, o tratamientos quirúrgicos cuando falla la terapéutica o hay presión social, e incluso radioterapia en casos donde desarrollan ginecomastia con hipersensibilidad al tratamiento hormonal del cáncer de próstata

Gynecomastia, defined as the growth of breast glandular tissue in men, appears from the neonatal to senile stage, can be unilateral or bilateral, and is of multifactorial cause, including those patients associated with the use of medications, where an imbalance in the testosterone ­ estrogen ratio. Relatively, idiopathic is the most common. Most regress spontaneously, neonatals due to loss of transplacental influx in the first weeks, and pubertal ones between 12 to 24 months. It presents as an increase in breast size, asymptomatic or with hypersensitivity due to inflammation during the growth of the mammary fibroglandular tissue, with an enormous psychological repercussion, especially in adolescence. The study and management is interdisciplinary and offered according to conditions and etiology. Those pubertal patients in whom it does not regress receive medical treatments, or surgical treatments when therapy fails or there is social pressure, and even radiotherapy in cases where they develop gynecomastia with hypersensitivity to hormonal treatment of prostate cancer

Switching of hormone therapies in breast cancer women / Avaliação da mudança do esquema hormonioterápico em mulheres com câncer de mama

Abstract Objective The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer. Methods This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017. Results From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, 'disease progression' was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, 'presence of side effects' was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities. Conclusion The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.

Resumo Objetivo O objetivo do presente estudo foi analisar os motivos que levaram às mudanças no esquema hormonioterápico (HT) em mulheres com câncer de mama. Métodos Estudo transversal retrospectivo realizado no Hospital da Mulher de Campinas e consequente pesquisa de prontuários de mulheres diagnosticados com câncer de mama entre janeiro de 2012 e janeiro de 2017. Resultados De 1.555 mulheres em tratamento com HT, 213 (13,7%) mulheres tiveram HT alterado, tamoxifeno para anastrozol ou vice-versa. A maioria das mulheres incluídas no presente estudo que tiveram mudança de HT tinha > 50 anos, estava na pós-menopausa, era caucasiana e tinha pelo menos uma comorbidade. Os principais motivos de troca de HT foram devido a 'progressão da doença', ocorrendo em 124 (58,2%) casos e a 'presença de efeitos colaterais' (n = 65; 30,5%). Das mulheres que sofreram efeitos colaterais, 24 (36,9%) apresentaram comorbidades. Conclusão O presente estudo demonstrou uma baixa taxa na alteração de tamoxifeno para anastrozol. Entre as razõesmais comuns para alterar a HT estava a progressão da doença, que inclui recorrência do câncer, metástase ou aumento do tumor. Os efeitos colaterais foram a segunda causa e, além disso, a idade e as comorbidades foram fatores de risco para efeitos colaterais.

Combination Effect of Tamoxifen and Ascorbic Acid Treatment on Breast Cancer Cells (MCF-7) and Cervical Cancer Cells (HeLa) Kesan Rawatan Kombinasi Tamoksifen dan Asid Askorbik ke atas Sel Kanser Payudara (MCF-7) dan Sel Kanser Serviks / Jurnal Sains Kesihatan Malaysia

@#Breast cancer and cervical cancer are among the leading causes of death among women in the world. Even though chemotherapy is available as cancer treatment, the development of drug resistance in both cancer cells has reduced the efficacy of chemotherapeutic drugs in such treatment. The current study was aimed to evaluate the cell viability of human breast cancer cells, MCF-7, and cervical cancer cells, HeLa upon the combination treatment of ascorbic acid and tamoxifen. The cell viability was measured using the MTT assay, with an incubation period of 72 hours in a humidified CO2 incubator. The concentrations of tamoxifen and ascorbic acid that reduced 50% of the cell population (IC50) were determined from the dose-response curve. The IC50 concentration was used to determine the cell viability in the treated cells. CompuSyn software was used to evaluate the combined effects towards both cells upon treatment and the results were calculated as combination index (CI). The data were analyzed using GraphPad Prism (version 7). Statistical analysis was performed using an independent t-test. The IC50 values of tamoxifen and ascorbic acid on MCF-7 cells were 14.53 µg/ml and 15.8 µg/ml respectively, while the IC50 values of tamoxifen and ascorbic acid on HeLa cells were 11.09 µg/ml and 202.3 µg/ml respectively. The combination of tamoxifen and ascorbic acid exerted a greater growth reduction percentage in both cells compared to tamoxifen alone. The results indicated that ascorbic acid synergizes the cytotoxic effect of tamoxifen at lower concentrations towards MCF-7 cells with a CI less than 1. However, the combination of tamoxifen and ascorbic acid exerted an antagonistic effect in HeLa cells, with a CI more than 1.

Effect of LINC00672 on sensitivity of breast cancer to tamoxifen and its related mechanisms / 中华内分泌外科杂志

Objective:To investigate the effect of long non-coding RNA (LncRNA) LINC00672 on sensitivity of breast cancer to tamoxifen and related mechanisms.Methods:Human breast cancer MCF-7 cells was treated in vitro to establish tamoxifen resistance (resistance group) and corresponding parental cell line (parent group) . The interfered LINC00672 and control cell line were constructed by Crisper-cas9 in resistant cells. (Interference 1 group, interference 2 group and control group) . The expression of LINC00672, Akt and HER2 mRNA was determined by real-time quantitative PCR. The expression levels of total Akt (Akt-pan) , phosphorylation of Akt (p-Akt) and HER2 were detected by Western blot.CCK-8 assay was used to detect cell resistance to tamoxifen.Results:The expressions of LINC00672, Akt and HER2 mRNA in the parental group were (1.000±0.086) , (1.000±0.254) and (1.000±0.208) , and the TAM IC 50 was (1.417±0.153) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the resistance group were (4.286±0.593) , (4.175±0.274) and (2.519±0.389) , and the TAM IC 50 was (12.029±1.016) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the control group were (1.000±0.093) , (1.000±0.090) and (1.000±0.097) , and the TAM IC 50 was (10.58±0.639) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the interference group 1 were (0.331±0.023) , (0.892±0.044) and (0.458±0.077) , and the TAM IC 50 was (6.250±0.836) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the interference group 2 were (0.304±0.016) , (0.919±0.050) and (0.416±0.080) , and the TAM IC 50 was (4.764±0.553) μmol/L. As compared with the parental group, the expressions of LINC00672, Akt and HER2 mRNA were significantly up-regulated ( P<0.01) in resistance group, the protein levels of Akt-pan, p-Akt and HER2 was up-regulated. The IC 50 value of tamoxifen was significantly increased in resistance group ( P<0.01) . As compared with the control group, the expression levels of LINC00672 and HER2 mRNA were significantly decreased in the interference group 1 and the interference group 2 ( P<0.01) , the levels of Akt was not significantly changed ( P>0.05) . The protein levels of p-Akt and HER2 were significantly decreased but there was no significant change in the expression of Akt-pan. The IC50 value of tamoxifen was significantly decreased ( P<0.01) . Conclusion:LINC00672 may be involved in the formation of tamoxifen resistance in breast cancer cells, and its underlying mechanism is related to the promotion of HER2/p-Akt pathway.

Yanghe Huayantang Reverses Tamoxifen Resistance in Breast Cancer Through ER/PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To explore the possible mechanism of Yanghe Huayantang in reversing the drug resistance of breast cancer by observing the effect of Yanghe Huayantang on the transplant tumor of tamoxifen （TAM）-resistant breast cancer and its influences on the interaction pathway of estrogen receptor （ER）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR）. Method:Fifty mice were randomly divided into 5 groups： blank group， model group， Yanghe Huayantang group， everolimus group， and Yanghe Huayantang+everolimus group. The model of kidney deficiency was established by bilateral ovariectomy， and the blank group was treated with sham operation. Three days after the establishment of the model， all the five groups of mice were inoculated with breast cancer TAM drug-resistant cells （MCF-7/TAM^-） to establish breast cancer TAM -resistant transplanted tumor model. After successful modeling， Yanghe Huayantang group received intragastric administration of Yanghe Huayantang （traditional Chinese medicine preparation 20 mL·kg^-1）， everolimus group received intraperitoneal injection of everolimus （10 mg·kg^-1）. Yanghe Huayantang + everolimus group received Yanghe Huayantang by intragastric administration and everolimus by intraperitoneal injection. The blank group and model group received intragastric administration and intraperitoneal injection of phosphate buffer （PBS）. Drug administration was lasted for 28 days in all groups， once a day. After administration， the tumor tissue was separated and weighed， and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of tumor tissue. Immunofluorescence and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of PI3K， Akt， mTOR， ER protein and mRNA in tumor tissue. Result:Compared with the model group， the tumor volume and tumor weight of Yanghe Huayantang group decreased significantly on the 12th， 20th and 28th days （<italic>P</italic><0.01）， and the tumor inhibition rate increased significantly （<italic>P</italic><0.01）.Yanghe Huayantang group significantly reduced the density of tumor cells and caused tumor cell necrosis. Compared with the model group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group inhibited the expression of PI3K， Akt， mTOR protein and mRNA （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the blank group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group all inhibited the protein and mRNA expression of ER， and mRNA expression of ER in Yanghe Huayantang+everolimus group was significantly lower than that in the model group （<italic>P</italic><0.01）. Conclusion:Yanghe Huayantang can inhibit the growth of TAM-resistant breast cancer. The mechanism may be that Yanghe Huayantang can reverse the TAM resistance of breast cancer by down-regulating the expression of key molecules of ER/PI3K/Akt/mTOR cross-signal pathway.

Effect of Shugan Yishen Prescription on Tamoxifen-resistant Cell Line from Exosome-mediated Crosstalk in Breast Cancer Microenvironment / 中国实验方剂学杂志

Objective:To explore the effect of Shugan Yishen prescription（SGYS） on the tamoxifen （TAM） -resistant cell line LCC9 by the intervention of exosome-mediated crosstalk in the breast cancer microenvironment. Method:Four groups of serum were set up， specifically， a blank group， a TAM （2 mg·kg^-1·d^-1） group，an SGYS（113.2 g·kg^-1·d^-1） group，and a combination group. The exosomes of LCC9 cells were extracted by ultracentrifugation and identified by transmission electron microscopy （TEM），nanoparticle tracking analysis （NTA）， and Western blot. Then the collected LCC9 exosomes （LCC9-EXO） were co-cultured with bone marrow mesenchymal stem cells（BMMSCs），and 10% of the above four groups of serum were added to the co-culture system. After 48 hours of co-culture，the exosomes of BMMSCs （BMMSCs-EXO） were extracted and incubated with LCC9 cells. Fluorescence microscope was used to observe the uptake of exosomes by cells. Cell counting kit-8 （CCK-8） assay，flow cytometry， and Transwell assay were used to detect the effects of drug-containing serum in the four groups on the proliferation，apoptosis， and migration of LCC9 cells. Western blot was used to detect the protein expression of CD24，CD44，human epidermal growth factor 2（HER2）， and estrogen receptor <italic>α</italic> （ER<italic>α</italic>） in each group. Result:Fluorescence microscope observed that LCC9-EXO could be taken up by BMMSCs，and BMMSCs-EXO could be taken up by LCC9 cells. CCK-8 assay revealed that compared with the TAM group，the SGYS group and the combination group showed reduced cell proliferation ability at each period （<italic>P</italic><0.05），especially the combination group，but no statistically significant difference between the SGYS group and the combination group was observed （<italic>P</italic><0.05）. Flow cytometry revealed that compared with the TAM group，the SGYS group and the combination group showed increased levels of apoptosis （<italic>P</italic><0.05）. Transwell assay revealed that compared with the TAM group，the SGYS group and the combination group showed decreased cell migration ability （<italic>P</italic><0.05）. Western blot revealed that compared with the TAM group，the SGYS group and the combination group showed up-regulated expression of ERα and CD24（<italic>P</italic><0.05），and down-regulated expression of HER2 and CD44 （<italic>P</italic><0.05）. The effect of the combination group on protein expression was superior to that of the SGYS group （<italic>P</italic><0.05）. Conclusion:SGYS reverses the TAM resistance of LCC9 cells by interfering with the crosstalk between BMMSCs-EXO and LCC9-EXO.

Tamoxifen treatment and its outcome in breast cancer patients at a hospital-based cancer registry in Kerala

Background: Endocrine therapy for breast cancer is directed at reducing oestrogen synthesis or alternatively blocking oestrogen receptors (ER) in tumour-sensitive tumors. Despite side effects, the use of systemic adjuvant therapy after local management of breast cancer substantially improves survival and reduces the risk of relapse. The study objective was to assess the recurrence of breast cancer and the complications seen in breast cancer patients on tamoxifen therapy at a hospital-based cancer registry, Thrissur, Kerala.Methods: After obtaining institutional ethical clearance, included 75 patients of histologically diagnosed breast carcinoma currently on tamoxifen, diagnosed in the year of 2016. Data was obtained from the patient files and by personal intimation.Results: Of the 75 patients on tamoxifen, four (5.33%) patients had history of recurrence. 22.6% of patients on tamoxifen were noted to have increased endometrial thickness. Other side effects noted were weight gain, TIA, bone pain and vaginal discharge.Conclusions: It was found that the recurrence rate at three years for the study population was 5.33%. More studies from developing countries, with larger sample size and clinical trials will give us more accurate information regarding the efficacy of the drug.

Caracterización de incontinencia urinaria en mujeres premenopáusicas con cáncer de mama en tratamiento con tamoxifeno por cinco años en el Instituto Nacional del Cáncer / Characterization of urinary incontinence in pre-menopausal women with breast cancer treated with tamoxifen for 5 years at the National Cancer Institute

INTRODUCCIÓN El cáncer de mama es el tipo de cáncer que se diagnostica con mayor frecuencia en mujeres y la segunda causa más común de muerte por cáncer en este género. Dentro de las indicaciones de tratamiento, se encuentran: cirugía, radioterapia, quimioterapia y terapia endocrina. Esta última se basa en el uso de tamoxifeno, cuyo uso de forma prolongada puede producir efectos secundarios como sequedad vaginal, ardor, irritación, picazón, disuria, incontinencia urinaria, entre otros OBJETIVO Caracterizar la incontinencia urinaria en mujeres premenopáusicas con cáncer de mama en tratamiento con tamoxifeno por 5 años en el Instituto Nacional del Cáncer MATERIAL Y MÉTODO Estudio descriptivo de corte transversal. Se incluyeron mujeres diagnosticadas con cáncer de mama inscritas y tratadas en el Instituto Nacional del Cáncer. Se aplicó cuestionario ICIQ ­SF a la población de estudio con el fin de caracterizar la presencia de incontinencia urinaria. Además, se calculó la proporción entre mujeres con incontinencia urinaria y nuliparidad/mujeres con incontinencia urinaria y paridad RESULTADOS Se evaluaron 15 pacientes. 93,33% presentaron incontinencia urinaria. El promedio de edad de mujeres con incontinencia urinaria fue de 51,21 (± 4,74) años. La razón de mujeres con nuliparidad/con paridad fue de 4:15 CONCLUSIÓN 99,33% de las pacientes presentaron incontinencia urinaria. Los resultados entregados en este estudio deben ser considerados como un elemento que contribuya a detectar la magnitud del problema en la población inscrita y tratada en el Instituto Nacional del Cáncer.

BACKGROUND Breast cancer is the type of cancer diagnosed most frequently in women, and the second most common cause of death from cancer in this gender. Within the indications of treatment, they are: surgery, radiotherapy, chemotherapy and endocrine therapy. The last is based on the use of tamoxifen, whose prolonged use can produce side effects such as vaginal dryness, burning, irritation, itching, dysuria, urinary incontinence, among others OBJECTIVE To characterize urinary incontinence in pre-menopausal women with breast cancer treated with tamoxifen for 5 years at the Instituto Nacional del Cáncer MATERIAL AND METHOD Descriptive cross-sectional study. We included women diagnosed with breast cancer enrolled and treated at the Instituto Nacional del Cáncer. The ICIQ -SF questionnaire was applied to the study population to characterize the presence of urinary incontinence. In addition, the proportion between women with urinary incontinence and nulliparity / women with urinary incontinence and parity was calculated RESULTS 93,33% presented urinary incontinence. The average age of women with urinary incontinence was 51,21 (± 4,74) years. The ratio of women with nulliparity / with parity was 4:15 CONCLUSION 99,33% of the patients presented urinary incontinence. The results delivered in this study should be considered as one element that helps to detect the magnitude of this problem in the population registered and treated in the Instituto Nacional del Cáncer. Keywords:

Formulation Development, Characterization and In-vitro Evaluation of Tamoxifen Loaded Liposomes

Background: The study was aimed to prepare and evaluate tamoxifen loaded controlled release liposomes to reduce the side effects of tamoxifen during cancer treatment. Methods: Different tamoxifen loaded liposomes were prepared by modified ether injection (MEIM) and thin film hydration method (TFHM) under prescribed conditions. The prepared liposomes were characterized by using optical microscopy, evaluating encapsulation efficiency, in-vitro and ex-vivo diffusion studies by using dialysis membrane and chicken intestinal sac respectively.Results: The data revealed that all of the liposomes were spherical in shape and stable under three physical conditions i.e. 4, 25 and 37 ± 2°C temperatures and 60 ±5% relative humidity. Additionally most of the liposomes followed zero order and class II release kinetics. It was also observed that with the increase of phospholipids and cholesterol, entrapment efficiency of liposome vesicles increased thus giving a controlled release drug delivery system but further increase reduced this efficiency at a certain level.Conclusion: The formulated control release liposomes might be a good drug delivery system for target oriented drug delivery with minimum side effects of tamoxifen during cancer treatment

Immunohistochemical assessment of symptomatic postmenopausal endometrial polyps in tamoxifen users and nonusers: a case control study

ABSTRACT BACKGROUND: Endometrial polyps are common in postmenopausal women, and the effect of tamoxifen use (a risk factor for endometrial polyps) on their pathogenesis is unclear. OBJECTIVES: To evaluate the expression of hormone receptors and markers for proliferation/apoptosis (Ki-67 and Bcl-2) in endometrial polyps in postmenopausal users and nonusers of tamoxifen. DESIGN AND SETTING: Cross-sectional analytical study in a tertiary-level academic hospital. METHODS: 46 women (14 tamoxifen users and 32 nonusers) with postmenopausal bleeding underwent hysteroscopic resection of endometrial polyps. Polyp samples were immunohistochemically assessed for detection of Ki-67, Bcl-2 and estrogen and progesterone receptors. RESULTS: Analysis on the glandular component of the polyps revealed progesterone receptor expression in the polyps of 96.9% of the nonusers of tamoxifen, and 92.3% of the tamoxifen users (P = 0.499). All polyps in nonusers and 92.3% of those in users were also positive for estrogen receptors (P = 0.295). Ki-67 was expressed in 75% of the polyps in the tamoxifen users and 82.8% of those in the nonusers. All endometrial polyps expressed Bcl-2. CONCLUSIONS: The immunohistochemical analysis on endometrial polyps demonstrated that, although tamoxifen is considered to be a risk factor for endometrial polyps, there were no significant differences in the expression of hormone receptors between users and nonusers of tamoxifen. There were no between-group differences in Ki-67 and Bcl-2 expression, and all patients displayed inhibition of apoptosis by Bcl-2, thus supporting the theory that polyps develop due to inhibition of apoptosis, and not through cell proliferation.