A real-world study of the effects of endocrine therapy on liver function in breast cancer / 中华外科杂志

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

Adesão à Terapia Hormonal Adjuvante com Tamoxifeno e Anastrozol utilizando ARMS-12 e MMAS-4 / Adherence to Adjuvant Hormone Therapy with Tamoxifen and Anastrozole using ARMS-12 and MMAS-4 / Adherencia a la Terapia Hormonal Adyuvante con Tamoxifeno y Anastrozol utilizando ARMS-12 y MMAS-4

Introdução: Entre os cânceres de mama, aproximadamente 75% das mulheres são receptores hormonais positivos, sendo estas mais propensas a responderem à hormonioterapia com anastrozol e tamoxifeno. Apesar de eficazes, apresentam taxas significativas de não adesão. Objetivo: Avaliar a adesão à terapia hormonal adjuvante com tamoxifeno e anastrozol em pacientes atendidos nos Ambulatórios da Mastologia e de Quimioterapia do Hospital São Paulo entre os anos de 2019 e 2020. Método: Estudo transversal com 102 mulheres, realizado entre os meses de setembro de 2019 e março de 2020. A adesão à terapia hormonal adjuvante foi avaliada utilizando-se as escalas Morisky Medication Adherence Scale (MMAS-4) e Adherence to Refills and Medications Scale of 12 items (ARMS-12). Resultados: A média de idade foi de 61,5 anos (59,3-63,6). Entre as pacientes, 27,7% faziam uso de tamoxifeno e 72,3% de anastrozol. Relataram desconforto em relação ao uso do medicamento 84,4%, sendo as ondas de calor (42,2%) e as dores articulares (55,9%) os mais frequentes. A escala de ARMS>12 foi pontuada por 79,2%; cerca de 90% das mulheres pontuaram a MMAS-4 até dois pontos, porém não houve diferença significativa entre os tipos de hormônios utilizados para escalas de adesão (p=0,815 e p=0,489). Conclusão: A adesão à hormonioterapia observada foi relativamente baixa, independentemente da endocrinoterapia, podendo essas pacientes estarem em risco de inadequação quanto à resposta clínica

Introduction: Among breast cancers, approximately 75% of women are hormone receptors-positive, and these are more likely to respond to hormone therapy with anastrozole and tamoxifen. Although effective, they have significant rates of non-adherence. Objective: To evaluate adherence to adjuvant hormone therapy with tamoxifen and anastrozole in patients consulted at the Mastology and Chemotherapy Outpatient Clinic of Hospital São Paulo between 2019 and 2020. Method: Cross-sectional study carried out with 102 women between September 2019 and March 2020. Adherence to hormone therapy was evaluated using the Morisky Medication Adherence Scale (MMAS-4) and Adherence to Refills and Medications Scale of 12 items (ARMS-12). Results: The mean age was 61.5 years (59.3-63.6). Among the patients, 27.7% used tamoxifen and 72.3%, anastrozole. 84.4% of them reported discomfort in using the medication, the most frequent were hot flashes (42.2%) and joint pain (55.9%). 79.2% scored the ARMS>12 scale, about 90% of the women scored MMAS-4 up to 2 points, but there was no significant difference between the types of hormones used for adhesion scales (p=0.815 to p=0.489). Conclusion: Adherence to hormone therapy was relatively low, regardless of the hormone used, and these patients may be at risk of inadequate clinical response

Introducción: Entre los cánceres de mama, aproximadamente el 75% de las mujeres son receptores hormonales positivos, y estas son más propensas a responder a la terapia hormonal con anastrozol y tamoxifeno. Aunque son eficaces, tienen tasas significativas de no adherencia. Objetivo: Evaluar la adhesión a la terapia hormonal adyuvante con tamoxifeno y anastrozol en pacientes atendidas en las Clínicas Ambulatorias de Mastología y Quimioterapia del Hospital São Paulo entre 2019 y 2020. Método: Este es un estudio transversal realizado con 102 mujeres entre septiembre de 2019 y marzo de 2020. La terapia hormonal adjunta se evaluó utilizando las escalas Morisky Medication Adherence Scale (MMAS-4) e Adherence to Refills and Medications Scale of 12 items (ARMS-12). Resultados: La edad media fue de 61,5 años (59,3-63,6). Entre las pacientes, el 27,7% utilizaron tamoxifeno y el 72,3% anastrozol. El 84,4% de ellas reportaron molestias en relación con el uso del medicamento, siendo los más frecuentes los sofocos (42,2%) y el dolor articular (55,9%). 79,2% puntuaron la escala ARMS>12, alrededor del 90% de las mujeres obtuvieron MMAS-4 hasta dos puntos, pero no hubo diferencia significativa entre los tipos de hormonas utilizadas para escalas de adhesión (p=0,815 a p=0,489). Conclusión: La adherencia de la terapia hormonal observada fue relativamente baja, independientemente de la hormona utilizada, y estas mujeres pueden estar en riesgo de respuesta clínica inadecuada

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.

Urinary incontinence and overactive bladder symptoms in women with breast cancer being treated with oral hormone therapy / Incontinência urinária e sintomas de bexiga hiperativa em mulheres com câncer de mama em tratamento com terapia hormonal oral

Abstract Objective: The objective of the present study is to observe the frequency and severity of urinary symptoms in women with breast cancer (BC) being treated with oral hormone therapy, associating them to drug adherence. Methods: The participants were interviewed once from June to October 2016. The evaluation of urinary symptoms was performed by two questionnaires: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB). Adherence was evaluated by the Morisky-Green method. Statistical analysis was performed by the Mann-Whitney test, linear regression, and Spearman correlation. Results: Fifty-eight women were interviewed: 42 treated with tamoxifen and 16 with aromatase inhibitor. Twenty-seven women (46.5%) presented urinary incontinence symptoms and 15 (25.8%) presented stress urinary incontinence (SUI). Fourteen (24.1%) women had symptoms of overactive bladder (OAB). There was no statistical difference in symptoms between both treatments and duration of treatments. Higher scores in the ICIQ-SF questionnaire were associated with low/medium adherence and advanced age. Higher scores in the ICIQ-OAB questionnaire were associated with low/medium adherence. Conclusion: The present study showed a high prevalence of urinary symptoms, such as urinary incontinence and OAB, associated with low/medium adherence and older age in women with BC being treated with oral hormone therapy. Health professionals should be alert to these symptoms since it could influence life quality and adherence to treatment.

Resumo Objetivo: O objetivo do presente estudo foi observar a frequência e a gravidade dos sintomas urinários em mulheres com câncer de mama em uso de terapia hormonal oral, associando estes com a adesão ao tratamento. Métodos: As pacientes foram entrevistadas uma única vez, entre junho e outubro de 2016. A avaliação dos sintomas urinários foi realizada por dois questionários: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF, na sigla em inglês) e o Questionário Sobre Bexiga Hiperativa (ICIQ-OAB, na sigla em inglês). A adesão foi avaliada pelo método Morisky-Green. A análise estatística foi realizada pelo teste de Mann-Whitney, regressão linear e correlação de Spearman. Resultados: Foram entrevistadas 58 mulheres: 42 tratadas com tamoxifeno e 16 com inibidor de aromatase. Vinte e sete mulheres (46,5%) apresentaram sintomas de incontinência urinária (IU) e 15 (25,8%) apresentaram incontinência urinária por estresse (IUS). Quatorze (24,1%) das mulheres tinham sintomas de bexiga hiperativa. Não houve diferença estatística nos sintomas entre os tratamentos e a duração dos tratamentos. Os escores mais elevados no questionário ICIQ-SF estiveram associados à baixa/média adesão e à idade avançada. Os escores mais elevados no questionário da ICIQ-OAB foram associados à baixa/média adesão. Conclusão: O presente estudo mostrou alta prevalência de sintomas urinários, como IU e bexiga hiperativa, associadas à baixa/média adesão e à idade mais avançada em mulheres com câncer de mama em tratamento com hormonioterapia oral. Os profissionais de saúde devem estar atentos a esses sintomas, pois eles podem influenciar a qualidade de vida e a adesão ao tratamento.

Anastrozole promotes implantation by altering the expression of paxillin and fak in rat luminal uterine epithelium / El anastrozol promueve la implantación alterando la expresión de paxilina y fak en el epitelio uterino luminal de rata

An alternative hyper-ovulator inducer to replace clomiphene citrate (CC) is needed as it is unsuitable for women with polycystic ovarian syndrome and is associated with low pregnancy rates. Anastrozole is an effective hyper-ovulator inducer, but has not been well researched. In order to determine the effectiveness of anastrozole as a hyper-ovulator inducer and to an extent compare it with CC in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, paxillin and FAK, which are uterine receptivity markers in the surface luminal uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that paxillin is localized in focal adhesions at the base of the uterine epithelial cells at day 1 of pregnancy whereas at day 6, paxillin disassembles from the basal focal adhesions and localizes and increases its expression apically. FAK is faintly expressed at the basal aspect of the uterine epithelial cells while moderately expressed at the cell-to-cell contact at day 1 in all groups from where it disassembles and relocates apically and becomes more intensely expressed at day 6 of pregnancy in untreated and anastrozole treated rats. Although paxillin is localized apically at day 6, its expression is significantly down-regulated with CC treatment suggesting its interference with the implantation process. These findings seem to suggest that anastrozole could favor implantation.

Para reemplazar el citrato de clomifeno (CC) es necesario un inductor de hiperovulación alternativo, ya que no es adecuado para mujeres con síndrome de ovario poliquístico y está asociado con tasas bajas de embarazo. El anastrozol es un inductor eficaz del hiper-ovulador, pero no se ha investigado adecuadamente. Con el fin de determinar la efectividad del anastrozol como inductor del hiper-ovulador y, en cierta medida, compararlo con CC en situaciones similares, este estudio determinó los efectos de estos fármacos en la expresión de las proteínas de adhesión focal, paxillin y FAK, uterinas marcadores de receptividad en la superficie luminal de células uterinas epiteliales, del día 1 y día 6 en ratas Wistar preñadas. Los resultados muestran que la paxilina se localiza en adherencias focales en la base de las células epiteliales uterinas en el día 1 del embarazo, mientras que en el día 6, la paxilina se desmonta de las adherencias focales basales y localiza y aumenta su expresión apicalmente. FAK se expresa débilmente en el aspecto basal de las células epiteliales uterinas, mientras que se expresa moderadamente en el contacto de célula a célula en el día 1 en todos los grupos, donde se separa y se reubica apicalmente y se expresa con mayor intensidad el día 6 de la preñez, en pacientes no tratados y tratados. ratas tratadas con anastrozol. Aunque la paxillina se localiza apicalmente en el día 6, su expresión está significativamente disminuida con el tratamiento con CC, lo que sugiere su interferencia con el proceso de implantación. Estos hallazgos sugieren que el anastrozol podría favorecer el proceso de implantación.

Effects of anastrozole on Ki-67 antigen expression in the vaginal epithelium of female rats in persistent estrus

OBJECTIVES: Aromatase inhibitors are the first-choice drugs for the treatment of hormone sensitive breast cancer. However, in addition to the scarcity of studies, there are controversies about their effects on vaginal epithelial cell proliferation in rats, especially those in persistent estrus. METHODS: To investigate vaginal epithelial cell proliferation by Ki-67 antigen expression, persistent estrus was induced in 42 randomly selected rats. These rats were randomly divided into 2 groups: group I (control, n=21), which received 0.1 mL of propylene glycol (vehicle) daily, and group II (experimental, n=21), which received 0.5 mg/kg or 0.125 mg/day of anastrozole diluted with 0.1 mL of propylene glycol. RESULTS: Light microscopy showed a higher concentration of cells with brown Ki-67 stained nuclei in the control compared to the experimental group. The mean percentage of Ki-67 stained nuclei per 500 cells in the vaginal epithelium was 68.64±2.64 and 30.46±2.00 [mean±standard error of the mean (SEM)] in the control and experimental groups, respectively (p<0.003). CONCLUSION: This study showed that anastrozole, at the dose and treatment duration selected, significantly decreased cell proliferation in the vaginal mucosa of the rats in persistent estrus.

The use of aromatase inhibitors in boys with short stature: what to know before prescribing?

ABSTRACT Aromatase is a cytochrome P450 enzyme (CYP19A1 isoform) able to catalyze the conversion of androgens to estrogens. The aromatase gene mutations highlighted the action of estrogen as one of the main regulators of bone maturation and closure of bone plate. The use of aromatase inhibitors (AI) in boys with short stature has showed its capability to improve the predicted final height. Anastrozole (ANZ) and letrozole (LTZ) are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450. In this review, we describe the pharmacokinetic profile of both drugs, discussing possible drug interactions between ANZ and LTZ with other drugs. AIs are triazolic compounds that can induce or suppress cytochrome P450 enzymes, interfering with metabolism of other compounds. Hydroxilation, N-dealkylation and glucoronidation are involved in the metabolism of AIs. Drug interactions can occur with azole antifungals, such as ketoconazole, by inhibiting CYP3A4 and by reducing the clearance of AIs. Antiepileptic drugs (lamotrigine, phenobarbital, and phenytoin) also inhibit aromatase. Concomitant use of phenobarbital or valproate has a synergistic effect on aromatase inhibition. Therefore, it is important to understand the pharmacokinetics of AIs, recognizing and avoiding possible drug interactions and offering a safer prescription profile of this class of aromatase inhibitors. Arch Endocrinol Metab. 2017;61(3):391-7.

Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review / Uso do anastrozol na quimioprevenção e no tratamento do câncer de mama: uma revisão da literatura

Summary Aromatase inhibitors have emerged as an alternative endocrine therapy for the treatment of hormone sensitive breast cancer in postmenopausal women. The use of third-generation inhibitors represented by exemestane, letrozol and anastrozole is currently indicated. Anastrozole is a nonsteroidal compound and a potent selective inhibitor of the aromatase enzyme. Although a few studies have shown that its pharmacodynamic and pharmacokinetic properties may be affected by interindividual variability, this drug has been recently used in all configurations of breast cancer treatment. In metastatic disease, it is currently considered the first-line treatment for postmenopausal women with estrogen receptor-positive breast tumors. Anastrozole has shown promising results in the adjuvant treatment of early-stage breast cancer in postmenopausal women. It has also achieved interesting results in the chemoprevention of the disease. Therefore, due to the importance of anastrozole both for endocrine treatment and chemoprevention of hormone-sensitive breast cancer in postmenopausal women, we proposed the current literature review in the SciELO and PubMed database of articles published in the last 10 years.

Resumo Os inibidores de aromatase têm emergido como uma endocrinoterapia alternativa para o tratamento de câncer de mama sensível a hormônios em mulheres pós-menopáusicas. A utilização de inibidores de terceira geração, representados por exemestano, letrozol e anastrozol, é atualmente indicada. Anastrozol é um composto não esteroide e um inibidor potente e seletivo da enzima aromatase. Embora alguns estudos tenham demonstrado que as suas propriedades farmacodinâmicas e farmacocinéticas podem ser afetadas pela variabilidade interindividual, esse fármaco tem sido recentemente utilizado em todas as configurações de tratamento do câncer de mama. Na doença metastática, é atualmente considerado o tratamento de primeira linha em mulheres pós-menopáusicas com tumores de mama e receptor de estrogênio positivo. O anastrozol tem mostrado resultados promissores no tratamento adjuvante do câncer de mama em estágio inicial em mulheres na pós-menopausa. Ele também conseguiu resultados interessantes na quimioprevenção da doença. Portanto, em virtude da importância do anastrozol tanto no tratamento endócrino quanto na quimioprevenção do câncer de mama hormoniossensível em mulheres na pós-menopausa, propusemos a atual revisão da literatura na base de dados SciELO e PubMed de artigos publicados nos últimos 10 anos.