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1.
Pan Afr Med J ; 40: 23, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733391

RESUMO

Occult breast cancer (OBC) is characterized by metastatic presentation of undetectable breast tumor on imaging exams. OBC is a rare disease (accounting for 0.3% to 1.0% of all breast cancers) that represents a major diagnostic challenge. The aim of this study was to report a case of OBC with primary presentation of multiple cutaneous metastases with subsequent emergence of bone metastasis. A 70-year female patient had multiple cutaneous metastatic lesions in the left cervical region, left breast, left axillary region, left subscapular region, in three chirodactylus of the right hand and three chirodactylus of the left hand. Imaging tests (mammogram, ultrasonography and magnetic resonance imaging of the breast) did not show alterations. Biopsy, histology sections and immunohistochemistry of the left cervical cutaneous lesion were compatible with OBC. After two years of anastrozole treatment (1mg/day), there was regression of all cutaneous lesions and stabilization of bone metastasis. OBC has a better prognosis. It may exhibit spontaneous regression or respond to less aggressive treatment strategies, as described in this case.


Assuntos
Anastrozol/administração & dosagem , Neoplasias da Mama/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Antineoplásicos Hormonais/administração & dosagem , Biópsia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/secundário , Resultado do Tratamento
2.
Gan To Kagaku Ryoho ; 48(10): 1259-1263, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34657059

RESUMO

BACKGROUND: In step with the aging of the Japanese population, late recurrence of hormone receptor positive (HR+) breast cancer occurring especially beyond 20 years after the initial diagnosis has been recognized as not rare anymore, as it has been occurring at a constant rate lately. The administration of an aromatase inhibitor with a CDK4/6 inhibitor has become the gold standard in Japan for cases of recurring HR+ breast cancer without severe visceral metastasis. CASE: A 73- year-old woman was diagnosed by chance with late recurrence of HR+ breast cancer 21 years after undergoing radical resection followed by adjuvant anastrozole for 5 years for stage Ⅲb right breast cancer. Asymptomatic multiple bone metastases on her ribs and sternum with bilateral lung metastasis and malignant effusion all disappeared while she was on a year- long administration of anastrozole and an optimal dose of abemaciclib(100 mg bid). However, because of the Grade 3 digestive adverse event that occurred at approximately 1 year of treatment, she could only maintain the treatment for up to 13 months. After then, no recurrence has been detectable for 6 months so far. CONCLUSION: CDK4/6 inhibitors, in combination with anastrozole, will play a pivotal role in the initial approach to elderly patients with HR+ late recurrence as a chemotherapy- free strategy.


Assuntos
Neoplasias da Mama , Idoso , Aminopiridinas , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Benzimidazóis , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Hormônios/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Nitrilas/uso terapêutico
3.
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
4.
DNA Cell Biol ; 40(8): 1039-1051, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165362

RESUMO

The interaction of calf thymus DNA (ct DNA) with anastrozole, which is acknowledged as an antineoplastic drug, has been enquired into in the absence and presence of histone H1, through the means of absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, and molecular modeling techniques. In addition, the effects of anastrozole on MCF 7 cell line have been thoroughly investigated. Fluorescence spectroscopy results have indicated that quenching mechanism of ct DNA-anastrozole are known as static quenching procedures, since the Stern-Volmer quenching constant (KSV) seems to face a decrease as the temperature is enhanced; this is a significant evidence for intercalative binding mode of anastrozole with ct DNA. Regarding the ternary system in the presence of H1, the constant of Stern-Volmer quenching was increased as the temperature was heightened. The thermodynamic parameters suggested that the binding could be characterized as exothermic by negative and positive enthalpy and entropy changes in both binary and ternary systems, respectively. It is vital to mention that hydrogen bonds and hydrophobic contributions play significant roles in anastrozole association to ct DNA in the absence and presence of H1. In accordance to the absorption spectroscopy and melting temperature curve outcomes, the binding mode of anastrozole with ct DNA in absence and presence of H1 was indicative of intercalative and nonintercalative bindings, respectively. The viscosity results as binary and ternary systems, which have been elucidated from a sensitive viscometer, have confirmed the fluorescence spectroscopy determinations. The intercalation of anastrozole to ct DNA seemed to be significantly related to an induced reduction in MCF-7 cell proliferation. The molecular modeling results have suggested that anastrozole could bind to H1 in ct DNA-H1 complex in ternary systems, which supports the conclusions that have been obtained from experimental data.


Assuntos
Anastrozol/farmacologia , Antineoplásicos/farmacologia , DNA/metabolismo , Histonas/metabolismo , Substâncias Intercalantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células MCF-7 , Ligação Proteica
5.
BMC Womens Health ; 21(1): 211, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016111

RESUMO

BACKGROUND: To study the effectiveness of an aromatase inhibitor (Anastrozole) associated with levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. METHODS: Prospective, randomized clinical trial. SETTING: University Hospital (single center). Elegibility criteria: Endometriomas > 3 × 4 cm, CA-125 > 35 U/mL and endometriosis symptoms. PATIENTS: Thirty-one women randomized to anastrozole + Mirena® + Conservative Surgery(CS) (n = 8), anastrozole + Mirena® + transvaginal ultrasound-guided puncture-aspiration (TUGPA) (n = 7), Mirena® + CS (n = 9), or Mirena® + TUGPA (n = 7). INTERVENTIONS: Anastrozole 1 mg/day and/or only Mirena® for 6 months; CS (ovarian and fertility-sparing) or TUGPA of endometriomas one month after starting medical treatment. MAIN OUTCOME MEASURES: Visual analogic scale for symptoms, CA-125 levels, ultrasound findings of endometriomas and recurrences. RESULTS: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients including anastrozole in their treatment (51%, 95% CI 33.3-68.7). For CA-125, the most significant decrease was observed in patients not taking anastrozole (73.8%, 95% CI 64.2-83.4 vs. 53.8%, 95% CI 25.7-81.6 under Mirena® + anastrozole). After CS for endometriosis, a reduction of ultrasound findings of endometriomas and long-term recurrence occurred, with or without anastrozole. At 4.2 ± 1.7 years (95% CI 3.57-4.85), 88% of the patients who underwent CS were asymptomatic, without medication or reoperation, compared to only 21% if TUGPA was performed, with or without anastrozole (p = 0.019). CONCLUSIONS: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces significantly the painful symptoms and delays recurrence, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time. Anastrozole and/or only Mirena® associated with TUGPA are not effective. TRIAL REGISTRATION: Eudra CT System of the European Medicines Agency (London, 29-Sept-2008) Nº EudraCT: 2008-005744-17 (07/11/2008). Date of enrolment of first patient: 15/01/2009.


Assuntos
Anticoncepcionais Femininos , Endometriose , Dispositivos Intrauterinos Medicados , Dispositivos Intrauterinos , Anastrozol/uso terapêutico , Endometriose/diagnóstico por imagem , Endometriose/tratamento farmacológico , Feminino , Humanos , Levanogestrel/uso terapêutico , Londres , Estudos Prospectivos
6.
Gan To Kagaku Ryoho ; 48(5): 701-703, 2021 May.
Artigo em Japonês | MEDLINE | ID: mdl-34006718

RESUMO

An 83‒year‒old woman received trastuzumab plus anastrozole as first‒line chemotherapy for inflammatory breast cancer in her left breast. Following the treatment, the induration and redness in her breast gradually improved; however, 2 days after receiving the 5th course of chemotherapy, she developed dyspnea and was referred to the emergency room. Her SpO2 was 88%; her KL‒6 level had increased to 2,613 U/mL; and a chest CT scan showed ground‒glass opacity in the bilateral lung fields, yielding a diagnosis of interstitial pneumonia requiring steroid pulse therapy. The dyspnea improved immediately after steroid administration, and the patient was discharged 20 days after hospitalization. Thereafter, the steroid dosage was gradually lowered to 5 mg/day. We discontinued steroid therapy after a chest CT confirmed the reduction of ground‒glass opacity. However, she was later readmitted for interstitial pneumonia for which she was readministered steroid pulse therapy. Trastuzumab‒induced interstitial pneumonia is rare, but we must be aware of the possibility that patients may develop severe pulmonary disorders or experience cardiotoxic effects.


Assuntos
Neoplasias Inflamatórias Mamárias , Doenças Pulmonares Intersticiais , Idoso de 80 Anos ou mais , Anastrozol , Feminino , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Trastuzumab/efeitos adversos
7.
Clin Pharmacol Ther ; 110(4): 1038-1049, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34048027

RESUMO

Aromatase inhibitors (AIs) are the treatment of choice for hormone receptor-positive early breast cancer in postmenopausal women. None of the third-generation AIs are superior to the others in terms of efficacy. We attempted to identify genetic factors that could differentiate between the effectiveness of adjuvant anastrozole and exemestane by examining single-nucleotide polymorphism (SNP)-treatment interaction in 4,465 patients. A group of SNPs were found to be differentially associated between anastrozole and exemestane regarding outcomes. However, they showed no association with outcome in the combined analysis. We followed up common SNPs near LY75 and GPR160 that could differentiate anastrozole from exemestane efficacy. LY75 and GPR160 participate in epithelial-to-mesenchymal transition and growth pathways, in both cases with SNP-dependent variation in regulation. Collectively, these studies identified SNPs that differentiate the efficacy of anastrozole and exemestane and they suggest additional genetic biomarkers for possible use in selecting an AI for a given patient.


Assuntos
Anastrozol/uso terapêutico , Androstadienos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antígenos CD/genética , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Lectinas Tipo C/genética , Antígenos de Histocompatibilidade Menor/genética , Estadiamento de Neoplasias , Seleção de Pacientes , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Receptores de Superfície Celular/genética , Receptores Acoplados a Proteínas G/genética , Resultado do Tratamento
8.
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
9.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803480

RESUMO

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D3 metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)2D3 analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Anastrozol/agonistas , Anastrozol/farmacologia , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Calcitriol/análogos & derivados , Calcitriol/farmacologia , Di-Hidroxicolecalciferóis/farmacologia , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos SCID , Ensaios Antitumorais Modelo de Xenoenxerto
10.
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
11.
J Med Case Rep ; 15(1): 207, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33910628

RESUMO

BACKGROUND: Adjuvant endocrine therapy is recommended for the treatment of hormone-receptor-positive breast cancer. Aromatase inhibitors are associated with significant musculoskeletal adverse effects, likely through growth hormone/insulin-like growth factor 1 modulation, while tamoxifen reduces insulin-like growth factor 1 production. We describe the case of a patient who was treated successfully with tamoxifen for her hormone-receptor-positive breast cancer and acromegaly. CASE PRESENTATION: A 57-year old White female with hormone-receptor-positive breast cancer was diagnosed with acromegaly. She received adjuvant endocrine therapy with anastrozole but could not tolerate this medication because of severe arthralgia, so she was switched to tamoxifen. Shortly after starting tamoxifen, the patient's musculoskeletal symptoms resolved and her insulin-like growth factor 1 levels normalized. She has remained in remission of her acromegaly and breast cancer since initiating tamoxifen. CONCLUSION: This case highlights the dual benefit of tamoxifen therapy in the treatment of hormone-receptor-positive breast cancer and acromegaly. Unlike anastrozole, tamoxifen has the benefit of lowering insulin-like growth factor 1 levels, which underscores its advantage in reducing adverse musculoskeletal symptoms during the treatment of hormone-receptor-positive breast cancer. We offer the first reported use of tamoxifen monotherapy for the successful treatment of acromegaly and hormone-receptor-positive breast cancer. While tamoxifen may offer an additional, oral option for acromegaly patients who do not respond to or tolerate conventional growth-hormone-lowering therapy, additional studies are necessary.


Assuntos
Acromegalia , Neoplasias da Mama , Acromegalia/tratamento farmacológico , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico
12.
Mayo Clin Proc ; 96(4): 1033-1040, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33814072

RESUMO

Breast cancer remains the most common cancer in women in the United States. For certain women at high risk for breast cancer, endocrine therapy (ET) can greatly decrease the risk. Tools such as the Breast Cancer Risk Assessment Tool (or Gail Model) and the International Breast Cancer Intervention Study risk calculator are available to help identify women at increased risk for breast cancer. Physician awareness of family history, reproductive and lifestyle factors, dense breast tissue, and history of benign proliferative breast disease are important when identifying high-risk women. The updated US Preventive Services Task Force and American Society of Clinical Oncology guidelines encourage primary care providers to identify at-risk women and offer risk-reducing medications. Among the various ETs, which include tamoxifen, raloxifene, anastrozole, and exemestane, tamoxifen is the only one available for premenopausal women aged 35 years and older. A shared decision-making process should be used to increase the usage of ET and must be individualized. This individualized approach must account for each woman's medical history and weigh the benefits and risks of ET in combination with the personal values of the patient.


Assuntos
Anastrozol/administração & dosagem , Neoplasias da Mama/prevenção & controle , Antagonistas de Estrogênios/administração & dosagem , Pessoal de Saúde/educação , Medicina Preventiva/educação , Cloridrato de Raloxifeno/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Tamoxifeno/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Currículo , Tomada de Decisão Compartilhada , Educação Médica Continuada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina Preventiva/métodos , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
13.
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
14.
Breast Cancer Res Treat ; 188(1): 215-223, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33656637

RESUMO

BACKGROUND: We investigated the association between body mass index (BMI) and breast cancer risk in women at increased risk of breast cancer receiving tamoxifen or anastrozole compared with placebo using data from the International Breast Cancer Intervention Studies [IBIS-I (tamoxifen) and IBIS-II (anastrozole)]. METHODS: Baseline BMI was calculated from nurse assessed height and weight measurements for premenopausal (n = 3138) and postmenopausal (n = 3731) women in IBIS-I and postmenopausal women in IBIS-II (n = 3787). The primary endpoint was any breast cancer event (invasive and ductal carcinoma in situ). We used Cox proportional hazards regression to calculate hazard ratios (HRs) for risk after adjustment for covariates. RESULTS: There were 582 (IBIS-I) and 248 (IBIS-II) breast cancer events [median follow-up = 16.2 years (IQR 14.4-17.7) and 10.9 years (IQR 8.8-13.0), respectively]. In adjusted analysis, women with a higher BMI had an increased breast cancer risk in both IBIS-I [HR = 1.06 per 5 kg/m2 (0.99-1.15), p = 0.114] and in IBIS-II [HR per 5 kg/m2 = 1.21 (1.09-1.35), p < 0.001]. In IBIS-I, the association between BMI and breast cancer risk was positive in postmenopausal women [adjusted HR per 5 kg/m2 = 1.14 (1.03-1.26), p = 0.01] but not premenopausal women [adjusted HR per 5 kg/m2 = 0.97 (0.86-1.09), p = 0.628]. There was no interaction between BMI and treatment group for breast cancer risk in either IBIS-I (p = 0.62) or IBIS-II (p = 0.55). CONCLUSIONS: Higher BMI is associated with greater breast cancer risk in postmenopausal women at increased risk of the disease, but no effect was observed in premenopausal women. The lack of interaction between BMI and treatment group on breast cancer risk suggests women are likely to experience benefit from preventive therapy regardless of their BMI. Trial registration Both trials were registered [IBIS-I: ISRCTN91879928 on 24/02/2006, retrospectively registered ( http://www.isrctn.com/ISRCTN91879928 ); IBIS-II: ISRCTN31488319 on 07/01/2005, retrospectively registered ( http://www.isrctn.com/ISRCTN31488319 )].


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Anastrozol , Índice de Massa Corporal , Feminino , Humanos , Incidência , Fatores de Risco , Tamoxifeno
15.
Br J Surg ; 108(3): 308-314, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33608712

RESUMO

BACKGROUND: The aim of this study was to investigate whether the PAM-50-based 46-gene assay carries prognostic value for risk of local recurrence of breast cancer. METHODS: The Austrian Breast and Colorectal Cancer Study Group (ABCSG) 8 RCT compared 5 years of tamoxifen with tamoxifen for 2 years followed by anastrozole for 3 years in postmenopausal women with endocrine receptor-positive breast cancer. This study included patients from the trial who had breast-conserving surgery for whom tumour blocks were available for PAM-50 analysis. RESULTS: Tumour blocks from 1204 patients who had breast-conserving surgery were available for the PAM-50 analysis, and 1034 of these received radiotherapy. After a median follow-up of 10.8 years, 23 local events had been observed, corresponding to an overall local recurrence risk of 2.2 per cent. Univariable competing-risk analysis demonstrated that patients at low risk according to PAM-50 analysis (risk-of-recurrence (ROR) score less than 57) had a significantly lower incidence of local recurrence than those in the high-risk group at 5 years (0.1 (95 per cent c.i. 0 to 0.7) versus 2.2 (0.9 to 4.6) per cent respectively; subhazard ratio (SHR) 17.18, 95 per cent c.i. 2.06 to 142.88; P = 0.009) and 10 years (0.9 (0.4 to 2.0) versus 3.8 (1.9 to 6.6) per cent; SHR 4.76, 1.72 to 13.17; P = 0.003). Multivariable analyses that included ROR score, age, tumour size, nodal status, type of surgery, tumor grade, and trial-specific endocrine therapy confirmed that ROR score was an independent prognostic factor for risk of local recurrence. Analysis of the women randomized to radiotherapy or control after breast conservation showed that PAM-50 was not predictive of radiotherapy effect. CONCLUSION: PAM-50 can be used as a prognostic tool for local recurrence risk in postmenopausal women with hormone receptor-positive breast cancer treated with endocrine therapy. The test was not predictive for the benefit of radiotherapy.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica/métodos , Recidiva Local de Neoplasia/genética , Fatores Etários , Idoso , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Linfonodos/patologia , Mastectomia Segmentar , Gradação de Tumores , Pós-Menopausa , Prognóstico , Radioterapia Adjuvante , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Tamoxifeno/uso terapêutico
16.
BMC Palliat Care ; 20(1): 28, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546678

RESUMO

BACKGROUND: Type I endometrial cancer is the most common gynaecological tumour in developed countries and its incidence is increasing also because of population aging. The aim of this work is to test the feasibility and safety of anastrozole as palliative treatment of endometrial cancer in elderly women ineligible for standard surgical treatment. METHODS: Patients with histological diagnosis of type I endometrial cancer not suitable for surgical treatment were enrolled in this pilot study. Anastrozole was administered 1 mg daily orally after performing an accurate clinical and radiological staging. Validated questionnaire and self-reported outcomes were used to evaluate quality of life and compliance during the study period. RESULTS: Eight patients with a mean age of 85 (range 80-88 years) were enrolled. All patients had endometrial cancer confined to the uterus, and none progression of disease was observed during the study period. A partial response to the therapy was reported in seven patients, while one patient had stable disease. Tumour symptoms improvement such as pain, vaginal bleeding and vaginal discomfort was reported. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average follow-up time was 18.25 months. Four women died for non oncological reasons, none death related to endometrial cancer was reported. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported. CONCLUSIONS: Our preliminary data suggested that the palliative use of anastrozole may be a suitable therapy for the proper management of early stages endometrial cancer in elderly women not suitable for surgical treatment with good compliance and tolerance. TRIAL REGISTRATION: 2013000840. Date of registration: 21/09/2013. URL: trials.sanmatteo.loc .


Assuntos
Neoplasias do Endométrio , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Anastrozol/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Nitrilas/uso terapêutico , Cuidados Paliativos , Projetos Piloto , Tamoxifeno , Triazóis/uso terapêutico
17.
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
18.
J Clin Endocrinol Metab ; 106(5): 1491-1500, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33513243

RESUMO

CONTEXT: Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration, and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens. OBJECTIVE: The objective was to study long-term treatment effects of an aromatase inhibitor. METHODS: Data from 7 boys with AEXS were retrospectively collected. Genetic analysis revealed upstream of CYP19A1 a 165 901 bp deletion in 4 German cousins, a 198 662 bp deletion in 2 Japanese brothers, and a 387 622 bp tandem duplication in a Japanese boy. RESULTS: All boys developed prepubertal gynecomastia, at median 9.0 years of age (range: 7.0-11.0). Height was +1.20 standard deviation score (SDS) (-0.24 to +1.98); predicted adult height was -1.29 SDS (-3.29 to +1.09). Four boys were treated with 1.0 mg of anastrozole daily, while 3 reached adult height untreated. Treatment with anastrozole was stopped after 5.6 years (4.0-6.8). Three treated boys exceeded their prognosis by 2.4, 6.9, and 8.1 cm, while 1 untreated boy fell below the prognosis by 8.6 cm. One treated with a low dose and 2 untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 to -0.29) and -0.15 SDS without (-2.31 to -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 to +0.52) and +0.54 SDS without (+0.23 to +1.30). CONCLUSION: Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by anastrozole promotes adult height in boys with AEXS.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/tratamento farmacológico , Inibidores da Aromatase/uso terapêutico , Aromatase/genética , Desenvolvimento Infantil/efeitos dos fármacos , Ginecomastia/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Erros Inatos do Metabolismo/tratamento farmacológico , Adolescente , Anastrozol/farmacologia , Anastrozol/uso terapêutico , Aromatase/metabolismo , Inibidores da Aromatase/farmacologia , Estatura/efeitos dos fármacos , Criança , Alemanha , Humanos , Japão , Masculino , Estudos Retrospectivos , Irmãos , Fatores de Tempo
19.
Rev Bras Ginecol Obstet ; 43(3): 185-189, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33465792

RESUMO

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.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Anastrozol/administração & dosagem , Anastrozol/efeitos adversos , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Registros Médicos , Participação do Paciente , Estudos Retrospectivos , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Adulto Jovem
20.
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
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