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1.
N Engl J Med ; 385(5): 395-405, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34320285

RESUMO

BACKGROUND: For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear. METHODS: In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture. RESULTS: Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84). CONCLUSIONS: In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).


Assuntos
Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Administração Oral , Idoso , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio , Receptores de Progesterona , Tamoxifeno/uso terapêutico
2.
Int J Mol Sci ; 22(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923802

RESUMO

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Coagulação Sanguínea , Neoplasias da Mama/tratamento farmacológico , Transição Epitelial-Mesenquimal , Inibidores da Agregação Plaquetária/efeitos adversos , Trombofilia/prevenção & controle , Adulto , Anastrozol/administração & dosagem , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Neoplasias da Mama/complicações , Células Cultivadas , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Iminas/administração & dosagem , Iminas/efeitos adversos , Iminas/uso terapêutico , Células MCF-7 , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Trombina/metabolismo , Trombofilia/tratamento farmacológico , Trombofilia/etiologia
3.
J Periodontal Res ; 56(4): 828-836, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33797064

RESUMO

BACKGROUND: Recent studies have shown that treatment with aromatase inhibitors contributes to an increased prevalence of periodontitis. OBJECTIVE: In this study, we assessed effects of the aromatase inhibitor anastrozole on cellular function of human gingival fibroblasts (HGFs) and endothelial cells. METHODS: Expression levels of collagen, extracellular matrix (ECM) proteins, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were examined in HGFs exposed to anastrozole. Furthermore, inflammatory responses in HGFs cultured with anastrozole were evaluated in the presence of Porphyromonas gingivalis lipopolysaccharide. We also evaluated the vascular permeability and vascular endothelial (VE)-cadherin expression of endothelial cells exposed to anastrozole. RESULTS: Anastrozole enhanced expression levels of collagen, ECM proteins, TIMPs, and inflammatory cytokines in HGFs, as well as vascular permeability of endothelial cells. In addition, anastrozole reduced expression levels of MMPs in HGFs and VE-cadherin in endothelial cells. CONCLUSION: These results suggest that anastrozole modulates various cellular functions in HGFs and endothelial cells.


Assuntos
Inibidores da Aromatase , Células Endoteliais , Anastrozol/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Células Cultivadas , Fibroblastos , Gengiva , Humanos , Porphyromonas gingivalis
4.
Cancer Sci ; 112(6): 2381-2392, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33686753

RESUMO

This post hoc analysis of MONARCH 2 and MONARCH 3 assesses the efficacy, safety, and pharmacokinetics (PK) of abemaciclib in combination with endocrine therapy (ET) in East Asian patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. MONARCH 2 and MONARCH 3 are global, randomized, double-blind, phase 3 studies of abemaciclib/placebo + fulvestrant and abemaciclib/placebo + nonsteroidal aromatase inhibitor (NSAI, anastrozole or letrozole), respectively. The East Asian population comprised 212 (31.7%) of the 669 intent-to-treat (ITT) population in the MONARCH 2 trial and 144 (29.2%) of the 493 ITT patients in the MONARCH 3 trial. In the East Asian population, median progression-free survival (PFS) was significantly prolonged in the abemaciclib arm compared with placebo in both MONARCH 2 (hazard ratio [HR], 0.520; 95% confidence interval [CI], 0.362 to 0.747; P < .001; median: 21.2 vs 11.6 months) and MONARCH 3 (HR, 0.326; 95% CI, 0.200 to 0.531, P < .001; median: not reached vs 12.82 months). Diarrhea (MONARCH 2: 90%; MONARCH 3: 88%) and neutropenia (MONARCH 2: 68%; MONARCH 3: 58%) were the most frequent adverse events observed in the East Asian populations. Abemaciclib exposures and PK were similar in East Asians and the non-East Asian populations of both trials. Abemaciclib in combination with ET in the East Asian populations of MONARCH 2 and MONARCH 3 provided consistent results with the ITT populations, demonstrating improvements in efficacy with generally tolerable safety profiles for patients with HR+, HER2- advanced breast cancer.


Assuntos
Aminopiridinas/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Benzimidazóis/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Fulvestranto/administração & dosagem , Aminopiridinas/efeitos adversos , Aminopiridinas/farmacocinética , Anastrozol/administração & dosagem , Anastrozol/efeitos adversos , Anastrozol/farmacocinética , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/farmacocinética , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fulvestranto/efeitos adversos , Fulvestranto/farmacocinética , Humanos , Letrozol/administração & dosagem , Letrozol/efeitos adversos , Letrozol/farmacocinética , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Receptor ErbB-2/genética , Resultado do Tratamento
5.
Gynecol Oncol ; 161(1): 160-165, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33608144

RESUMO

BACKGROUND: Aromatase inhibitors are standard of care for low-grade endometrial stromal sarcomas (LGESS), based on very high response rates reported in retrospective studies. We evaluated the activity of anastrozole in recurrent/metastatic LGESS patients enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER±)/progesterone receptor (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER ± PR + ve LGESS with measurable disease, treated until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 15 eligible patients were enrolled. CBR at 3 months was 73% (95% CI: 48-89.1%); unchanged at 6 months. Best response was 26.7%, including complete response in one (6.7%; 95% CI 1.2-29.8%), partial response in three (20%, 95% CI 7.1-45.2%) and stable disease in seven (46.7%). Four patients ceased treatment by 3 months due to progression. Median PFS was not reached (25th percentile: 2.9 months (95% CI: 1.2-NR)). PFS was 73.3%, 73.3% and 66% at 6, 12, and 18 months, respectively. Six patients remained on treatment for an average of 44.2 months (range 34.5-63.6) up until data cut. Toxicity was as expected, with 3 patients stopping due to adverse effects. CONCLUSION: The 26.7% objective response rate with anastrozole is lower than reported in retrospective series, but the CBR was high and durable. The results underscore the importance of prospective trials in rare cancers.


Assuntos
Anastrozol/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Tumores do Estroma Endometrial/tratamento farmacológico , Idoso , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Tumores do Estroma Endometrial/metabolismo , Tumores do Estroma Endometrial/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Intervalo Livre de Progressão , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
6.
Br J Cancer ; 124(8): 1373-1378, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33495601

RESUMO

BACKGROUND: Anastrozole has been associated with substantial accelerated bone mineral density (BMD) loss during active treatment. METHODS: One thousand four hundred and ten women were included in a BMD substudy and stratified into three strata according to their baseline T-score at spine or femoral neck. The primary objective of this analysis was to investigate whether DXA BMD at the spine and hip changed two years after treatment cessation (between years 5 and 7) in those who did not receive risedronate. RESULTS: Five- and seven-year BMD data were available for a total of 528 women who did not receive risedronate. In women with normal BMD at baseline, an increase in BMD at the lumbar spine after anastrozole withdrawal was observed 1.25% (95% CI 0.73 to 1.77) (P = 0.0004), which was larger than in those on placebo (0.14% (-0.29 to 0.56))). At the hip, BMD remained unchanged between years 5 and 7 for those previously on anastrozole but continued to a decrease in those who had been randomised to placebo (-1.35% (-1.70 to -0.98)). CONCLUSIONS: These are the first results reporting BMD changes after stopping anastrozole in a breast cancer prevention setting. Our results show that the negative effects of anastrozole on BMD in the preventive setting are partially reversible.


Assuntos
Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/prevenção & controle , Colo do Fêmur/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Absorciometria de Fóton , Idoso , Anastrozol/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Estudos de Casos e Controles , Método Duplo-Cego , Feminino , Colo do Fêmur/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Coluna Vertebral/efeitos dos fármacos
7.
Pharmacogenet Genomics ; 31(1): 1-9, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32649577

RESUMO

OBJECTIVES: Based on our previous findings that postmenopausal women with estrone (E1) and estradiol (E2) concentrations at or above 1.3 pg/ml and 0.5 pg/ml, respectively, after 6 months of adjuvant anastrozole therapy had a three-fold risk of recurrence, we aimed to identify a single-nucleotide polymorphism (SNP)-based model that would predict elevated E1 and E2 and then validate it in an independent dataset. PATIENTS AND METHODS: The test set consisted of 322 women from the M3 study and the validation set consisted of 152 patients from MA.27. All patients were treated with adjuvant anastrozole, had on-anastrozole E1 and E2 concentrations and genome-wide genotyping. RESULTS: SNPs were identified from the M3 genome-wide association study. The best model to predict the E1-E2 phenotype with high balanced accuracy was a support vector machine model using clinical factors plus 46 SNPs. We did not have an independent cohort that is similar to the M3 study with clinical, E1-E2 phenotypes and genotype data to test our model. Hence, we chose a nested matched case-control cohort (MA.27 study) for testing. Our E1-E2 model was not validated but we found the MA.27 validation cohort was both clinically and genomically different. CONCLUSIONS: We identified a SNP-based model that had excellent performance characteristics for predicting the phenotype of elevated E1 and E2 in women treated with anastrozole. This model was not validated in an independent dataset but that dataset was clinically and genomically substantially different. The model will need validation in a prospective study.


Assuntos
Anastrozol/efeitos adversos , Neoplasias da Mama/genética , Predisposição Genética para Doença , Recidiva Local de Neoplasia/genética , Adulto , Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/sangue , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/patologia , Estradiol/sangue , Estrona/sangue , Feminino , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único/genética
8.
Support Care Cancer ; 29(1): 187-191, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32328775

RESUMO

BACKGROUND: Anti-estrogen therapy is an effective intervention for preventing reoccurrence of hormone receptor-positive breast cancer in women. However, the side effects of anti-estrogen therapy, including urogenital symptoms, have been reported to cause significant morbidity. There is controversial data, mainly due to small sample sizes, reporting on the safety and efficacy of using vaginal estrogen to treat urogenital symptoms in patients on aromatase inhibitor therapy. METHODS: We proposed a prospective trial to measure the change in blood estradiol levels in postmenopausal women with hormone receptor-positive breast cancer undergoing treatment with aromatase inhibitors when treated with vaginal estrogen preparation, Estring, for their urogenital symptoms. Only 8 prospective patients were enrolled, and the study was amended to include 6 retrospective patients who were treated similarly. Blood estradiol levels were measured at baseline and at week 16 for all patients. RESULTS: The median age for all patients was 55 years, and the majority of them were treated with anastrozole. There was no significant difference between baseline and week 16 estradiol levels (p = 0.81). In addition, patients in the prospective group reported subjective improvement in their vaginal dryness symptoms questionnaires. CONCLUSIONS: The vaginal estrogen preparation, Estring, did not cause persistent elevations in serum estradiol levels and might be a safer option for women with significant urogenital symptoms requiring estrogen therapy. IMPLICATIONS FOR CANCER SURVIVORS: Vaginal estrogen preparation, Estring, might be an option for women with hormone receptor positive breast cancer who have persistent urogenital symptoms.


Assuntos
Anastrozol/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/sangue , Moduladores de Receptor Estrogênico/uso terapêutico , Estrogênios/efeitos adversos , Administração Intravaginal , Anastrozol/efeitos adversos , Moduladores de Receptor Estrogênico/efeitos adversos , Estrogênios/administração & dosagem , Estrogênios/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Estudos Retrospectivos , Doenças Vaginais/induzido quimicamente , Doenças Vaginais/tratamento farmacológico
9.
Breast Cancer Res Treat ; 183(2): 365-372, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32632513

RESUMO

PURPOSE: Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer. METHODS: One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia. RESULTS: More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole (P = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia. CONCLUSIONS: Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.


Assuntos
Anastrozol/efeitos adversos , Aromatase/genética , Artralgia/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/genética , Letrozol/efeitos adversos , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/efeitos adversos , Artralgia/induzido quimicamente , Artralgia/genética , Biomarcadores/análise , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Suspensão de Tratamento/estatística & dados numéricos
10.
Clin Interv Aging ; 15: 691-693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546987

RESUMO

Chemobrain is one of the problems that may arise during or after treatment and there is currently no specific treatment for this condition. Our case was a 76-year-old female patient who presented to our clinic with complaints of forgetfulness that did not affect daily living activities for the last year. Breast cancer was diagnosed in 2013 and she has been receiving anastrozole treatment for 6 years after local mass excision surgery and radiotherapy. After a comprehensive geriatric evaluation, cognitive impairment due to systemic cancer therapy was detected and treatment was started with Theracurmin 90 mg twice a day therapy. After 3-months of Theracurmin therapy, she had no cognitive improvement during the follow-up. This case report demonstrated that Theracurmin treatment may be a new option for chemobrain.


Assuntos
Anastrozol , Neoplasias da Mama/terapia , Transtornos Cognitivos , Cognição/efeitos dos fármacos , Curcumina/administração & dosagem , Radioterapia , Idoso , Anastrozol/administração & dosagem , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/patologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Feminino , Avaliação Geriátrica/métodos , Humanos , Mastectomia Segmentar/métodos , Nootrópicos/administração & dosagem , Radioterapia/efeitos adversos , Radioterapia/métodos , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(2): e18688, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914067

RESUMO

INTRODUCTION: Estrogen is a key factor in breast cancer carcinogenesis, and reductions in its synthesis can decrease breast cancer risk. Anastrozole can reduce plasma estrogen levels by inhibiting the enzyme aromatase, and is approved for adjuvant treatment of breast cancer. We report a case of pulmonary cryptococcosis in a patient who was treated with anastrozole for an early-stage tumor. This case is of special interest because the patient achieved a better curative effect after the administration of anastrozole was discontinued. PATIENT CONCERNS: A 61-year-old woman was found to have multiple pulmonary nodules on chest computed tomography (CT) after being treated for 5 months with anastrozole as an adjuvant breast cancer therapy. A biopsy of the largest lesion of the right lung showed cryptococcus fungal bodies with granulomatous inflammation, so the patient was diagnosed with pulmonary cryptococcosis. She was treated with fluconazole (400 mg/day) for 1 month, but a follow-up CT scan of chest showed no improvement. DIAGNOSIS: Pulmonary cryptococcosis. INTERVENTIONS: Because the pulmonary cryptococcosis was not improving, the administration of anastrozole was discontinued. Fluconazole was continued. OUTCOMES: The pulmonary lesions diminished in size 2 months after discontinuing anastrozole. The patient continued taking fluconazole for a total of 6 months without re-administration of anastrozole, and the lesions of pulmonary cryptococcosis almost disappeared. CONCLUSION: This case of pulmonary cryptococcosis may have been induced by a decrease in estrogen level caused by the aromatase inhibitor, anastrozole. Treatment of pulmonary cryptococcosis with concurrent anastrozole use may be ineffective, and it may be better to discontinue the aromatase inhibitor.


Assuntos
Anastrozol/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Criptococose/etiologia , Pneumopatias Fúngicas/etiologia , Anastrozol/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade
12.
Lancet ; 395(10218): 117-122, 2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31839281

RESUMO

BACKGROUND: Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period. METHODS: IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer. FINDINGS: 3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed. INTERPRETATION: This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality. FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.


Assuntos
Anastrozol/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Administração Oral , Adulto , Idoso , Anastrozol/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento , Reino Unido/epidemiologia
13.
BMJ Case Rep ; 12(11)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31780604

RESUMO

Anastrozole is an aromatase inhibitor that has been used more frequently over the last decade especially for oestrogen receptor-positive breast cancer. It has a relatively safe side effect profile. However, occasionally it has been associated with serious adverse events. Here, we present the case of a 58-year-old woman who presented with significantly elevated liver enzymes 4 years after starting anastrozole. She was not taking any other medications and an extensive workup did not reveal any other cause for her liver injury. The patient's liver enzymes normalised after discounting the anastrozole. She scored 4 on the updated Roussel Uclaf Causality Assessment Method grading system which was possible for drug-induced liver injury. A review of the literature revealed six prior cases of anastrozole-related liver injury. Anastrozole should be considered as a possible culprit in patients who develop an unexplained acute liver injury.


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Tempo
14.
Anticancer Res ; 39(8): 4393-4398, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366535

RESUMO

BACKGROUND/AIM: Metastatic breast cancer (MBC) represents a wide spectrum of heterogeneous conditions with different secondary spread sites, time to relapse and biology. MBC is still considered an incurable disease despite the fact that survival rates have improved in the last years. Cutaneous metastases are a rare site for metastatic spread and indicate advanced disease. The aim of this study is to demonstrate the excellent therapeutic result following endocrine therapy only in MBC with just skin involvement. CASE REPORT: We present a case of an 82-year-old woman with no family history of breast cancer (BC), who was diagnosed with de novo metastatic estrogen/progesterone receptor-positive and HER2-negative invasive lobular BC. The only site of secondary spread was the skin. She was treated with just endocrine therapy for 116 months with which she achieved and maintained long-term complete clinical response (CR). DISCUSSION: To our knowledge this is the only case of lobular BC with de novo metastatic manifestation as multiple skin metastases, which achieved CR following the aromatase inhibitor treatment (anastrozole) with such impressive long-term overall survival.


Assuntos
Anastrozol/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso de 80 Anos ou mais , Anastrozol/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário
15.
J Clin Nurs ; 28(23-24): 4560-4571, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31469461

RESUMO

AIMS AND OBJECTIVES: To examine and compare the differences in symptoms and symptom clusters between postmenopausal women with early-stage breast cancer who did and did not receive chemotherapy prior to aromatase inhibitor (AI) therapy. BACKGROUND: Women with breast cancer often experience multiple concurrent symptoms during AI therapy. The burden of symptoms prior to AI is associated with nonadherence to cancer treatment. To date, few studies have comprehensively explored the symptoms and symptom clusters occurring prior to AI therapy. DESIGN: Secondary analysis of a prospective repeated-measures study. METHODS: The sample comprised postmenopausal women (N = 339) with breast cancer who would receive AI therapy with or without chemotherapy. We collected information on 48 symptoms after surgery or chemotherapy but before AI therapy using different symptom assessment tools. Mann-Whitney U tests were used to compare the differences in the severity of symptoms between groups. Exploratory factor analysis (EFA) was conducted to determine symptom clusters. This study followed STROBE guidelines. RESULTS: The most severe symptoms among women with breast cancer prior to AI therapy were breast sensitivity, unhappy with the appearance of my body, general aches and pain, joint pain and muscle stiffness. Women who received chemotherapy prior to AI therapy experienced significantly higher severity of 22 symptoms than women who did not receive chemotherapy. Through EFA seven distinct symptom clusters were revealed in both groups: cognitive, musculoskeletal, psychological, vasomotor, weight, sexual and urinary, with additional gastrointestinal symptom cluster been identified in women who received chemotherapy. CONCLUSIONS: This study indicates the presence of symptoms among women with breast cancer prior to AI therapy, with higher severity of symptoms and greater number of symptom clusters for women who received chemotherapy. RELEVANCE TO CLINICAL PRACTICE: Nurses should assess and be aware of symptoms and symptom clusters existed prior to AI therapy and manage them in advance.


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Idoso , Anastrozol/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/complicações , Neoplasias da Mama/fisiopatologia , Estudos de Casos e Controles , Feminino , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Pós-Menopausa , Estudos Prospectivos , Síndrome
16.
Gynecol Oncol ; 154(3): 531-538, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31227223

RESUMO

OBJECTIVE: Treatment options are limited for patients with recurrent/metastatic low-grade ovarian cancers (LGOCs) and serous borderline ovarian tumors (SBOTs) as response rates to chemotherapy are low. A subset of patients appears to derive clinical benefit from antiestrogens, but most studies have been retrospective and clinical benefit rates (CBR) remain uncertain. The primary aim of PARAGON was to prospectively investigate the CBR of anastrozole, an aromatase inhibitor, in patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive LGOC and SBOT. METHODS: Post-menopausal women with ER-positive and/or PR-positive recurrent/metastatic LGOCs and SBOTs and evaluable disease by RECIST v1.1 or GCIG CA125 criteria were treated with anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Thirty-six patients were enrolled. Clinical benefit at 3 months (primary endpoint) was observed in 23 patients (64%, 95% CI 48%-78%) and was similar at 6 months (61%, 95% CI 43%-75%). The median duration of clinical benefit was 9.5 months (95% CI 8.3-25.8). Best study response was partial response by RECIST in 5 patients (14%), stable disease in 18 patients (50%) with progressive disease in 13 patients (36%). Median PFS was 11.1 months (95% CI 3.2-11.9). Anastrozole was well-tolerated. Patients with evidence of clinical benefit at 3 months reported less pain, fatigue, and improved physical and role functioning as early as 1 month of commencing treatment. CONCLUSIONS: Anastrozole was associated with a CBR of 61% of patients with recurrent ER-positive and/or PR-positive LGOC or SBOT for at least 6 months with acceptable toxicity.


Assuntos
Anastrozol/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Pós-Menopausa , Intervalo Livre de Progressão , Estudos Prospectivos , Qualidade de Vida , Receptores de Progesterona/metabolismo , Adulto Jovem
17.
Clin Endocrinol (Oxf) ; 91(1): 124-130, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31070802

RESUMO

OBJECTIVE: Anastrozole, an aromatase inhibitor, has been used off-label in males with short stature to delay bone maturation. No studies have examined anastrozole's effect on bone mineral density (BMD) or body composition in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Our objective was to evaluate anastrozole's effect on BMD and visceral adipose tissue (VAT) in children with CAH. DESIGN: Total body BMD (TBMD) and L2-L4 BMD Z-scores were adjusted for height-for-age Z-scores (TBMDHAZ and L2-L4HAZ ). Hydrocortisone doses (mg/m2 /d) were averaged over the previous year. Comparison of treated vs not treated with anastrozole used linear regression adjusting for age, pubertal status, sex, CAH type, years on hydrocortisone, BMI Z-scores and bone age Z-scores. PATIENTS: We compared 25 children with CAH treated with anastrozole (mean age 11.3 [SD 3.0] years, 56% males) vs 31 children with CAH not treated with anastrozole (13.5 [SD 4.6], 29%). Participants underwent a pubertal exam, bone age X-ray and dual X-ray absorptiometry (DXA) scan. RESULTS: Average bone age Z-score of 4.3 SDs on beginning anastrozole decreased to 1.9 SDs at time of DXA exam (P = 0.0004) 5.2 (SD 2.2) years later. TBMD Z-scores (P = 0.51), L2-L4 BMD Z-scores (P = 0.66), VAT (P = 0.38), TBMDHAZ Z-scores (P = 0.66) and L2-L4HAZ Z-scores (P = 0.41) did not differ between children treated vs not treated with anastrozole. CONCLUSION: Anastrozole significantly reduced bone age advancement in children with CAH and advanced bone age (>2SDs) without adverse effects on BMD or VAT. Longitudinal studies of anastrozole in children with CAH are needed to validate these findings.


Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Anastrozol/efeitos adversos , Anastrozol/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Gordura Intra-Abdominal/efeitos dos fármacos , Absorciometria de Fóton , Adolescente , Hiperplasia Suprarrenal Congênita/metabolismo , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , Hidrocortisona/efeitos adversos , Hidrocortisona/uso terapêutico , Masculino
18.
Bone ; 124: 83-88, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028957

RESUMO

Anastrozole has been shown to prevent breast cancer in postmenopausal women at high risk of the disease, but has been associated with substantial accelerated loss of bone mineral density (BMD) and increased fractures. Here, we investigate the effect of risedronate on BMD after 5 years of follow-up in the IBIS-II prevention trial. 1410 women were enrolled in the bone sub-study and stratified into three strata according to the lowest baseline T-score at spine or femoral neck. The objective was to compare the effect of oral risedronate (35 mg weekly) versus placebo in osteopenic women in stratum II who were randomised to anastrozole in the main study. 258 osteopenic, postmenopausal women at high risk of developing breast cancer for whom baseline and follow-up bone mineral density measurements were available. 5-year mean BMD change at the lumbar spine for osteopenic women randomised to anastrozole and risedronate was -0.4% compared to -4.2% for those not on risedronate (P < 0.0001) but not significantly different between risedronate users and non-users at the hip (P = 0.2). 5-year mean PINP change was -20% for those randomised to anastrozole and risedronate compared to 3% for those not on risedronate but on anastrozole (P < 0.0001). Our results confirm the bone loss associated with the use of anastrozole and show that anastrozole-induced BMD loss in the spine can be controlled with risedronate treatment. However, our results suggest that weekly oral risedronate is unable to completely prevent anastrozole induced bone loss at the hip.


Assuntos
Anastrozol/efeitos adversos , Doenças Ósseas Metabólicas/epidemiologia , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/prevenção & controle , Neoplasias da Mama/epidemiologia , Ácido Risedrônico/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/sangue , Reabsorção Óssea/fisiopatologia , Feminino , Fraturas Ósseas/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Placebos , Pró-Colágeno/sangue , Ácido Risedrônico/farmacologia , Fatores de Risco
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