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1.
Zhonghua Yan Ke Za Zhi ; 57(3): 232-236, 2021 Mar 11.
Artigo em Chinês | MEDLINE | ID: mdl-33721964

RESUMO

By reviewing the recent articles regarding the ocular side effect of tamoxifen when treating breast cancer and glioma, this article summarized the incidence and the potential mechanism of the side effects of tamoxifen, and the specific ocular toxicity including keratopathy, cataract, retinopathy, optic neuropathy. This review would provide guidance for clinical ophthalmologists to early identify and appropriately manage tamoxifen induced ocular diseases. (Chin J Ophthalmol, 2021, 57: 232-236).


Assuntos
Neoplasias da Mama , Doenças Retinianas , Neoplasias da Mama/tratamento farmacológico , Olho , Humanos , Tamoxifeno/efeitos adversos , Neuropatia Óptica Tóxica
2.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542023

RESUMO

We report a case of ischaemic stroke in a 34-year-old male recreational bodybuilder following a 3-month period of anabolic androgenic steroid (AAS) use and 1-month period of 'post-cycle therapy' (tamoxifen and clomiphene citrate), the latter treatments aimed at restoring normal endogenous testosterone production after initial AAS use. We hypothesise a transient drug-related prothrombotic state with paradoxical embolisation via an atrial septal defect which was later found on bubble echocardiogram. We highlight a rare but important cause of stroke in younger patients which is relevant given the increasing use of AAS misuse among casual fitness enthusiasts. We explore the various possible mechanisms by which AAS use can increase ischaemic stroke risk in such patients.


Assuntos
Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/diagnóstico por imagem , Doping nos Esportes , Exercício Físico/fisiologia , /diagnóstico por imagem , Congêneres da Testosterona/efeitos adversos , Administração Intravenosa , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Clomifeno/administração & dosagem , Clomifeno/efeitos adversos , Ecocardiografia , Antagonistas de Estrogênios/administração & dosagem , Antagonistas de Estrogênios/efeitos adversos , Comunicação Interatrial/cirurgia , Humanos , Masculino , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos
3.
Cochrane Database Syst Rev ; 12: CD007245, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33348436

RESUMO

BACKGROUND: Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. OBJECTIVES: To determine the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. SEARCH METHODS: We searched the following databases on 29 June 2020; The Cochrane Gynaecology and Fertility Group specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature. We searched the Cochrane Breast Cancer Group specialised register on 4 March 2020. We also searched two trials registers, checked references for relevant trials and contacted study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with breast cancer on adjuvant tamoxifen that compared the effectiveness of the LNG-IUS with endometrial surveillance versus endometrial surveillance alone on the incidence of endometrial pathology. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer), diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. We rated the overall certainty of evidence using GRADE methods. MAIN RESULTS: We included four RCTs (543 women analysed) in this review. We judged the certainty of the evidence to be moderate for all of the outcomes, due to imprecision (i.e. limited sample sizes and low event rates). In the included studies, the active treatment arm was the 20 µg/day LNG-IUS plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS probably reduces the incidence of endometrial polyps compared to the control group over both a 12-month period (Peto odds ratio (OR) 0.22, 95% confidence interval (CI) 0.08 to 0.64, I² = 0%; 2 RCTs, n = 212; moderate-certainty evidence) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). For long-term follow-up, this suggests that if the incidence of endometrial polyps following endometrial surveillance alone is assumed to be 23.5%, the incidence following LNG-IUS with endometrial surveillance would be between 3.8% and 10.7%.  The LNG-IUS probably slightly reduces the incidence of endometrial hyperplasia compared with controls over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). This suggests that if the chance of endometrial hyperplasia following endometrial surveillance alone is assumed to be 2.8%, the chance following LNG-IUS with endometrial surveillance would be between 0.1% and 1.9%. However, it should be noted that there were only six cases of endometrial hyperplasia. There was insufficient evidence to reach a conclusion regarding the incidence of endometrial cancer in tamoxifen users, as no studies reported cases of endometrial cancer. At 12 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting compared to the control group (Peto OR 7.26, 95% CI 3.37 to 15.66; I² = 0%; 3 RCTs, n = 376; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 1.7%, the chance following LNG-IUS with endometrial surveillance would be between 5.6% and 21.5%. By 24 months of follow-up, abnormal vaginal bleeding or spotting occurs less frequently than at 12 months of follow-up, but is still more common in the LNG-IUS group than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10; I² = 0%; 2 RCTs, n = 233; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 4.2%, the chance following LNG-IUS with endometrial surveillance would be between 4.4% and 23.9%. By 60 months of follow-up, there were no cases of abnormal vaginal bleeding or spotting in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). As a result, there is probably little or no difference in these outcomes between the LNG-IUS treatment group and the control group.  AUTHORS' CONCLUSIONS: The LNG-IUS probably slightly reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. Data were lacking on whether the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available RCTs that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.


Assuntos
Neoplasias da Mama/prevenção & controle , Hiperplasia Endometrial/prevenção & controle , Neoplasias do Endométrio/prevenção & controle , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Recidiva Local de Neoplasia/prevenção & controle , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/prevenção & controle , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Intervalos de Confiança , Anticoncepcionais Femininos/administração & dosagem , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/epidemiologia , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Levanogestrel/efeitos adversos , Recidiva Local de Neoplasia/mortalidade , Pólipos/induzido quimicamente , Pólipos/epidemiologia , Pólipos/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamoxifeno/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Hemorragia Uterina/epidemiologia , Útero/efeitos dos fármacos
4.
Maturitas ; 141: 71-81, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33036706

RESUMO

BACKGROUND: Side-effects of hormone therapy can impair the physical health of breast cancer survivors. Exercise has been clearly shown to improve the quality of life of breast cancer survivors. Less is known about the effects of exercise on physical outcomes for breast cancer survivors receiving hormone therapy. OBJECTIVE: To investigate the effects of exercise on physical outcomes of breast cancer survivors receiving hormone therapy. METHODS: Five electronic databases were searched by two authors using the terms "Breast Neoplasms" [MeSH] and "Tamoxifen" [MeSH] and "Aromatase Inhibitors" [MeSH] and "Exercise" [MeSH]. Randomized and non-randomized clinical trials were included. Risk of bias was assessed by the Cochrane Collaboration tool and ROBINS-I, and the quality of evidence was evaluated using GRADE. Pooled effects were reported as standardized mean differences (SMDs) and 95 % confidence intervals (CIs) using a random effects model. RESULTS: Eleven studies were included in the meta-analysis. Two hundred and fourteen breast cancer survivors receiving hormone therapy, tamoxifen, or aromatase inhibitors participated in interventions based on aerobic plus resistance exercise or walking activity. The physical outcomes reported in the articles were: cardiorespiratory fitness, pain, bone mineral density, grip strength, and body fat percentage. Exercise effects were found only for cardiorespiratory fitness (SMD = 0.37; 95 % CI: 0.11; 0.63; I2 = 93 %) and pain (SMD = -0.55; IC95 % -1.11; -0.00; I2 = 80 %), with low quality of evidence. No effects were observed for the other variables. CONCLUSIONS: Aerobic plus resistance exercise had positive effects on cardiorespiratory fitness and pain in breast cancer survivors receiving hormone therapy. However, high-quality randomized clinical trials are required to confirm this finding.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/reabilitação , Sobreviventes de Câncer , Exercício Físico , Tamoxifeno/efeitos adversos , Densidade Óssea , Neoplasias da Mama/tratamento farmacológico , Terapia por Exercício , Feminino , Humanos , Qualidade de Vida , Sobreviventes , Caminhada
5.
Adv Exp Med Biol ; 1252: 175-179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32816279

RESUMO

Malignancy may unfortunately present quite early in a woman's life. In the case of breast cancer, rescue of the breast cancer patient's life is the top priority, but after completion of the effective treatment , the question about the ability to accomplish a pregnancy arises. The treatment strategies in breast cancer patients include surgical interventions, chemotherapy , radiotherapy, hormonal therapy and other special types of mainly targeted biologic therapies. Under normal circumstances, surgery for breast cancer does not involve any intervention in the ovaries or the uterus. Thus, even after an extended operation, the anatomic integrity of the gynecological system is guaranteed, and fertility is unaffected.The chemotherapeutic factors that influence fertility are the drug category used, the total dose given, the patient's age at treatment , the drug combination and finally whether targeted therapy is used or not. Alkylating agents are considered to be the most toxic ones. In young breast cancer patients there is a trend to modify regimens to achieve less gonadotoxicity.Evidence regarding tamoxifen, the main used endocrine drug, is scarce and controversial on its direct effect on ovarian reserve. There are not enough studies on the impact of aromatase inhibitors on fertility. Also, HER2-directed agents have not yet demonstrated significant ovarian toxicity and there are scarce data on their effect on fertility.


Assuntos
Neoplasias da Mama/terapia , Preservação da Fertilidade , Fertilidade/fisiologia , Inibidores da Aromatase/efeitos adversos , Feminino , Humanos , Infertilidade Feminina/etiologia , Reserva Ovariana/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/fisiologia , Gravidez , Tamoxifeno/efeitos adversos
6.
J Fr Ophtalmol ; 43(8): 727-730, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32620415

RESUMO

We report a case of a patient treated with tamoxifen 20mg daily as hormone therapy for breast cancer. On regular ophthalmological follow-up, tamoxifen maculopathy was detected on SD-OCT (Spectral Domain Optic Coherence Tomography, Carl Zeiss Meditec®), so the medication was discontinued. Despite discontinuation of the medication, the maculopathy progressed over time. We have been following our patient for seven years. Tamoxifen may produce a toxic maculopathy which may progress despite discontinuation of the medication. We consider our case interesting, given the lengthy follow-up of the patient with sequential SD-OCT images. To the best of our knowledge, our case represents the longest follow-up period for a patient with tamoxifen maculopathy. Moreover, we would like to stress the importance of screening in asymptomatic patients on this medication, in order to detect early pathological signs.


Assuntos
Monitorização Fisiológica , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/diagnóstico , Tamoxifeno/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Macula Lutea/efeitos dos fármacos , Macula Lutea/patologia , Degeneração Macular/induzido quimicamente , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Monitorização Fisiológica/métodos , Doenças Retinianas/patologia , Tamoxifeno/administração & dosagem , Tomografia de Coerência Óptica
7.
Proc Natl Acad Sci U S A ; 117(32): 19578-19589, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32727894

RESUMO

The CreER/LoxP system is widely accepted to track neural lineages and study gene functions upon tamoxifen (TAM) administration. We have observed that prenatal TAM treatment caused high rates of delayed delivery and fetal mortality. This substance could produce undesired results, leading to data misinterpretation. Here, we report that administration of TAM during early stages of cortical neurogenesis promoted precocious neural differentiation, while it inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, synaptic formation, and cortical patterning in neonatal and postnatal offspring. Mechanistically, by employing single-cell RNA-sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays, we show TAM could exert these drastic effects mainly through dysregulating the Wnt-Dmrta2 signaling pathway. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of TAM on corticogenesis, suggesting that care must be taken when using the TAM-induced CreER/LoxP system for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains.


Assuntos
Encéfalo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/patologia , Tamoxifeno/efeitos adversos , Animais , Encéfalo/embriologia , Encéfalo/patologia , Diferenciação Celular , Proliferação de Células , Giro Denteado/efeitos dos fármacos , Giro Denteado/patologia , Feminino , Ventrículos Laterais/efeitos dos fármacos , Ventrículos Laterais/patologia , Camundongos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , RNA-Seq , Análise de Célula Única , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
8.
PLoS One ; 15(7): e0236506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730287

RESUMO

BACKGROUND: Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer. METHODS: This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group. RESULTS: Median treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients. CONCLUSIONS: Tamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fígado Gorduroso/diagnóstico , Tamoxifeno/efeitos adversos , Adulto , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Duração da Terapia , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Tamoxifeno/uso terapêutico
9.
Folia Med Cracov ; 60(1): 45-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658211

RESUMO

Takotsubo cardiomyopathy (TCM) represents an acute systolic left ventricular dysfunction typically triggered by severe psychological or physical stress. Oncological patients due to emotional distress of the diagnosis, proinflammatory and prothrombotic nature of cancer and also physical stress often following complex anticancer therapies are at high-risk of TCM. Moreover, there are also few reports of TCM associated with oncological treatment, mostly chemotherapy. Recent data from large registries indicate a surprisingly high incidence of malignancy in TCM, significant differences in clinical characteristics and unfavorable short- and long-term clinical outcomes in this specific group of patients. Therefore, we present two case reports of TCM that occurred during active anticancer therapy. Both women were admitted with suspicion of acute coronary syndrome. The first patient underwent mastectomy two years before due to hormone receptor-positive breast cancer and on admission she was during adjuvant hormonotherapy with tamoxifen. The admission of the second patient was preceded by fifteen fractions of adjuvant external beam radiotherapy due to intermediate-risk endometrial cancer after radical hysterectomy. Based on coronary angiography type I of acute coronary syndrome was excluded. Both patients negated stressful situations in the period immediately before the symptoms onset. Within hospital course baseline apical ballooning observed in both cases fully recovered and enabled subsequent completion of oncological treatment in accordance with adopted treatment protocols without recurrence of TCM. To our knowledge, presented cases are the first reports showing direct relationship between TCM and adjuvant hormonotherapy with tamoxifen or pelvic radiotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia/efeitos adversos , Radioterapia/efeitos adversos , Cardiomiopatia de Takotsubo/etiologia , Tamoxifeno/efeitos adversos , Idoso , Feminino , Humanos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/fisiopatologia
10.
Nature ; 583(7817): 620-624, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669709

RESUMO

Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.


Assuntos
Neoplasias da Mama/dietoterapia , Neoplasias da Mama/tratamento farmacológico , Dietoterapia/métodos , Jejum/fisiologia , Fulvestranto/uso terapêutico , Animais , Fatores Biológicos/sangue , Neoplasias da Mama/patologia , Dieta Saudável/métodos , Modelos Animais de Doenças , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Feminino , Fulvestranto/administração & dosagem , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Células MCF-7 , Camundongos Endogâmicos NOD , Camundongos SCID , PTEN Fosfo-Hidrolase/metabolismo , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Receptores Estrogênicos , Receptores de Progesterona , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Comput Assist Tomogr ; 44(4): 485-489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32558766

RESUMO

PURPOSE: To evaluate tamoxifen-related endometrial changes in premenopausal female patients with diffusion-weighted magnetic resonance imaging (DWI). METHODS: This prospective study was performed on 71 premenopausal female patients (mean age, 41 years) who were receiving tamoxifen therapy. All patients underwent magnetic resonance imaging with DWI of the pelvis and hysteroscopic-guided endometrial biopsy. The apparent diffusion coefficient (ADC) values of the endometrial plate were calculated and correlated with pathological results. RESULTS: The mean ADCs of tamoxifen-related benign endometrial lesions (1.35 ± 0.19 and 1.32 ± 0.13 × 10 mm/s) were significantly higher (P = 0.001) than those of normal endometrial plate (0.95 ± 0.11 and 0.93 ± 0.11 × 10 mm/s) by both reviewers, respectively. The cutoff ADC values used to differentiate tamoxifen-related benign endometrial lesions from normal endometrium were 1.07 and 1.02 × 10 mm/s with areas under the curve of 0.94 and 0.93 and accuracy of 94.4 and 95.8 by both reviewers, respectively. The mean ADC values of endometrial polyp (EP) (1.44 ± 0.19 and 1.42 ± 0.22 × 10 mm/s) were significantly higher (P = 0.001) than those of endometrial hyperplasia (EH) (1.25 ± 0.19 and 1.23 ± 0.19 × 10 mm/s) by both reviewers, respectively. The cutoff ADC values used to differentiate EP from EH were 1.38 × 10 and 1.36 × 10 mm/s with areas under the curve of 0.81 and 0.77 and accuracy of 80% and 70% by both reviewers, respectively. There was an insignificant difference in ADC value between typical and atypical EH. The ADC values of endometrial cancer (0.80 and 0.78 × 10 mm/s) were lower than those of tamoxifen-related benign endometrial lesions. The final diagnosis was normal endometrium (n = 36), benign endometrial lesions either EH (n = 17), or EP (n = 16), and endometrial cancer in only 2 patients. CONCLUSIONS: We concluded that DWI helps in detection and characterization of different tamoxifen-related endometrial changes in the premenopausal female patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Hiperplasia Endometrial/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico por imagem , Endométrio/efeitos dos fármacos , Tamoxifeno/efeitos adversos , Adulto , Imagem de Difusão por Ressonância Magnética , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Pessoa de Meia-Idade , Variações Dependentes do Observador , Pré-Menopausa , Estudos Prospectivos , Tamoxifeno/uso terapêutico
13.
Expert Opin Pharmacother ; 21(12): 1493-1504, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32496137

RESUMO

INTRODUCTION: Despite its rarity, male breast cancer shows a steadily rising incidence. Given the absence of ad hoc prospective randomized clinical trials, treatment strategies are based on extrapolation from female breast cancer recommendations or solely on population-based data. AREAS COVERED: This review discusses the current treatment landscape for male breast cancer in the adjuvant and in the metastatic setting. The authors also discuss the biology and genomic landscape of male breast cancer. Original research and review articles, relative to the period 2010-2019, were included in the review of the literature. EXPERT OPINION: There is a major medical need to include male patients with breast cancer in prospective clinical trials. The call to equality in breast cancer care can be pursued via two divergent paths: (i) a gender-neutral delivery of breast cancer information and (ii) the creation of separate sections, for the more common female breast cancer and for the rare male ones. We propose to differentiate male breast cancer care, acknowledging unique onco-sexual and social needs that can be only partially shared.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama Masculina/tratamento farmacológico , Tamoxifeno/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama Masculina/patologia , Ensaios Clínicos como Assunto , Dano ao DNA , Reparo do DNA , Humanos , Masculino , Receptor ErbB-2/antagonistas & inibidores , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Resultado do Tratamento
15.
Breast Cancer Res Treat ; 181(2): 347-359, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32274665

RESUMO

PURPOSE: Sexual dysfunction is an important concern of premenopausal women with early breast cancer. We investigated predictors of sexual problems in two randomized controlled trials. METHODS: A subset of patients enrolled in TEXT and SOFT completed global and symptom-specific quality-of-life indicators, CES-Depression and MOS-Sexual Problems measures at baseline, six, 12 and 24 months. Mixed models tested the association of changes in treatment-induced symptoms (baseline to 6 months), depression at 6 months, and age at randomization with changes in sexual problems over 2 years. RESULTS: Sexual problems increased by 6 months and persisted at this level. Overall, patients with more severe worsening of vaginal dryness, sleep disturbances and bone or joint pain at 6 months reported a greater increase in sexual problems at all time-points. Depression scores were significantly associated with sexual problems in the short-term. All other symptoms had a smaller impact on sexual problems. Age was not associated with sexual problems at any time-point. CONCLUSION: Among several key symptoms, vaginal dryness, sleep disturbance, and bone and joint pain significantly predicted sexual problems during the first 2 years. Early identification of these symptoms may contribute to timely and tailored interventions.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Transtorno Depressivo/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Transtornos do Sono-Vigília/epidemiologia , Tamoxifeno/efeitos adversos , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Transtorno Depressivo/induzido quimicamente , Transtorno Depressivo/patologia , Feminino , Seguimentos , Saúde Global , Humanos , Incidência , Agências Internacionais , Pessoa de Meia-Idade , Pré-Menopausa , Prognóstico , Qualidade de Vida , Disfunções Sexuais Fisiológicas/patologia , Transtornos do Sono-Vigília/induzido quimicamente , Transtornos do Sono-Vigília/patologia
16.
Drugs Aging ; 37(5): 349-358, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32227289

RESUMO

Breast cancer is a disease of aging, and the incidence of breast cancer is projected to increase dramatically as the global population ages. The majority of breast cancers that occur in older adults are hormone-receptor positive, human epidermal growth factor receptor-2 (HER2)-negative phenotypes, with favorable tumor biology; yet, because of underrepresentation in clinical trials, less evidence is available to guide the complex care for this population. Providing care for older patients with metastatic breast cancer, with coexisting medical conditions, increased risk of treatment toxicity, and frailty, remains a clinical challenge in oncology. In this review, we provide an overview of the current evidence from clinical trials and subanalyses of older adults with hormone receptor-positive, HER2-negative metastatic breast cancer, highlighting data on the safety and efficacy of oral therapies, including endocrine therapy alone or in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and mammalian target of rapamycin (mTOR) inhibitors. In addition, we note the significant underrepresentation of older and frail adults in these studies. Current and future directions in research for this special population, in order to address significant knowledge gaps, include the need to improve long-term adherence to hormonal and targeted therapy, prospective clinical trials that capture clinical and biological aging endpoints, and the need for a multidisciplinary approach with integration of geriatric and oncology principles.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Superfície Celular/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Avaliação Geriátrica , Humanos , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico
17.
Yonsei Med J ; 61(4): 317-322, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233174

RESUMO

PURPOSE: To evaluate factors associated with endometrial pathology during tamoxifen use in premenopausal breast cancer (BC) patients. MATERIALS AND METHODS: We reviewed the medical records of premenopausal BC patients treated with tamoxifen who underwent endometrial biopsy with or without hysteroscopy. Clinical characteristics were compared between women with endometrial pathology (endometrial hyperplasia or cancer) and those with normal histology or endometrial polyps. RESULTS: Among 284 endometrial biopsies, endometrial hyperplasia was diagnosed in 7 patients (2.5%), endometrial cancer was diagnosed in 5 patients (1.8%), normal histology was noted in 146 patients (51.4%), and endometrial polyp was present in 114 patients (40.1%). When comparing women with endometrial cancer (n=5) to women with normal histology, abnormal uterine bleeding was more common (p=0.007), and endometrial thickness was greater (p=0.007) in women with endometrial cancer. Chemotherapy for BC was also more common in patients with endometrial cancer (p=0.037). When comparing women with endometrial polyps and those with endometrial hyperplasia or cancer, the presence of abnormal uterine bleeding was more common in patients with endometrial hyperplasia or cancer (p<0.001); however, tamoxifen duration and endometrial thickness did not differ significantly between the two groups. CONCLUSION: In premenopausal BC patients treated with tamoxifen, abnormal uterine bleeding, increased endometrial thickness, and chemotherapy for BC were associated with the occurrence of endometrial cancer. These findings may provide useful information for gynecologic surveillance and counseling during tamoxifen treatment in premenopausal BC patients.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Pólipos/induzido quimicamente , Pré-Menopausa , Tamoxifeno/efeitos adversos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Biópsia , Hiperplasia Endometrial/diagnóstico por imagem , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Endométrio/diagnóstico por imagem , Endométrio/patologia , Feminino , Humanos , Histeroscopia , Pessoa de Meia-Idade , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores de Risco , Tamoxifeno/uso terapêutico , Fatores de Tempo , Doenças Uterinas , Neoplasias Uterinas/induzido quimicamente , Neoplasias Uterinas/patologia
18.
Ann Rheum Dis ; 79(5): 581-586, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32161056

RESUMO

OBJECTIVES: To examine the risk of incident breast cancer in women with rheumatoid arthritis (RA), and the risk of RA in women with a history of breast cancer, taking antihormonal treatment for breast cancer into account. METHODS: Using nationwide Swedish registers, women with new-onset RA diagnosed in 2006-2016 were identified and analysed using a cohort and a case-control design. Each patient with RA was matched on age, sex and place of residence to five randomly selected subjects from the general population. Through register linkages, we collected information on breast cancer, breast cancer risk factors (reproductive history and hormone replacement therapy) and socio-economy. The relative risk of breast cancer after RA was assessed using Cox regression, and the relative risk of RA in women with a history of breast cancer was assessed using conditional logistic regression. RESULTS: The risk of incident breast cancer in women with RA was reduced and the association was not attenuated by adjustment for breast cancer risk factors (HR=0.80, 95% CI 0.68 to 0.93). The risk of RA in women with a history of breast cancer was similarly reduced (OR=0.87, 95% CI 0.79 to 0.95). Women with breast cancer treated with tamoxifen (OR=0.86, 95% CI 0.62 to 1.20) or aromatase inhibitors (OR=0.97, 95% CI 0.69 to 1.37) did not have an increased risk of RA compared with women with breast cancer treated differently. CONCLUSIONS: The decreased occurrence of breast cancer in patients with RA is present already before RA diagnosis; these reduced risks are not readily explained by hormonal risk factors. Adjuvant antihormonal therapy for breast cancer does not seem to increase RA risk.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Artrite Reumatoide/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Sistema de Registros , Tamoxifeno/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Antineoplásicos Hormonais/administração & dosagem , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Suécia , Tamoxifeno/administração & dosagem
20.
JAMA Netw Open ; 3(3): e201541, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32207833

RESUMO

Importance: The association between exposure to hormone-modulating therapy (HMT) as breast cancer treatment and neurodegenerative disease (NDD) is unclear. Objective: To determine whether HMT exposure is associated with the risk of NDD in women with breast cancer. Design, Setting, and Participants: This retrospective cohort study used the Humana claims data set from January 1, 2007, to March 31, 2017. The Humana data set contains claims from private-payer and Medicare insurance data sets from across the United States with a population primarily residing in the Southeast. Patient claims records were surveyed for a diagnosis of NDD starting 1 year after breast cancer diagnosis for the duration of enrollment in the claims database. Participants were 57 843 women aged 45 years or older with a diagnosis of breast cancer. Patients were required to be actively enrolled in Humana claims records for 6 months prior to and at least 3 years after the diagnosis of breast cancer. The analyses were conducted between January 1 and 15, 2020. Exposure: Hormone-modulating therapy (selective estrogen receptor modulators, estrogen receptor antagonists, and aromatase inhibitors). Main Outcomes and Measures: Patients receiving HMT for breast cancer treatment were identified. Survival analysis was used to determine the association between HMT exposure and diagnosis of NDD. A propensity score approach was used to minimize measured and unmeasured selection bias. Results: Of the 326 485 women with breast cancer in the Humana data set between 2007 and 2017, 57 843 met the study criteria. Of these, 18 126 (31.3%; mean [SD] age, 76.2 [7.0] years) received HMT, whereas 39 717 (68.7%; mean [SD] age, 76.8 [7.0] years) did not receive HMT. Mean (SD) follow-up was 5.5 (1.8) years. In the propensity score-matched population, exposure to HMT was associated with a decrease in the number of women who received a diagnosis of NDD (2229 of 17 878 [12.5%] vs 2559 of 17 878 [14.3%]; relative risk, 0.89; 95% CI, 0.84-0.93; P < .001), Alzheimer disease (877 of 17 878 [4.9%] vs 1068 of 17 878 [6.0%]; relative risk, 0.82; 95% CI, 0.75-0.90; P < .001), and dementia (1862 of 17 878 [10.4%] vs 2116 of 17 878 [11.8%]; relative risk, 0.88; 95% CI, 0.83-0.93; P < .001). The number needed to treat was 62.51 for all NDDs, 93.61 for Alzheimer disease, and 69.56 for dementia. Conclusions and Relevance: Among patients with breast cancer, tamoxifen and steroidal aromatase inhibitors were associated with a decrease in the number who received a diagnosis of NDD, specifically Alzheimer disease and dementia.


Assuntos
Antineoplásicos Hormonais , Inibidores da Aromatase , Neoplasias da Mama , Moduladores de Receptor Estrogênico , Doenças Neurodegenerativas , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Comorbidade , Moduladores de Receptor Estrogênico/administração & dosagem , Moduladores de Receptor Estrogênico/efeitos adversos , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/mortalidade , Estudos Retrospectivos , Fatores de Risco , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico
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