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1.
J Urol ; 205(1): 60-67, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32856962

RESUMO

PURPOSE: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). RESULTS: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months). CONCLUSIONS: Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.


Assuntos
Doença de Alzheimer/epidemiologia , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Demência/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/prevenção & controle , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Cognição/efeitos dos fármacos , Demência/induzido quimicamente , Demência/prevenção & controle , Esquema de Medicação , Humanos , Masculino , Neoplasias da Próstata/patologia , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo
2.
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.
Crit Rev Oncol Hematol ; 156: 103114, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33045493

RESUMO

BACKGROUND: Extended endocrine therapy (EET) with aromatase inhibitors (AIs) therapy can further reduce the risk of recurrence in breast cancer patients. But the conclusion that whether EET with AIs increases the risk of some side effects compared with nonextended endocrine therapy (NEET) is still controversial and not exhaustive. METHODS: We searched for Randomized controlled trials (RCT) trials published in EMBASE and PubMed between March 2008 and December 2019. Studies comparing the side effects of adjuvant EET with those of NEET were included. The objective was to determine whether EET with AIs increases the risk of side effects compared with NEET. RESULTS: Overall, 11 trials comprising 24,187 participants were identified. EET with AIs increased the risk of cardiotoxicity [odds ratio (OR) 1.19, 95 % confidence interval (CI) 1.04-1.36; P < 0.05; 438 vs 423], bone pain (OR 1.18, 95 % CI 1.02-1.36; P < 0.05; 446 vs 404), osteoporosis (OR 1.53, 95 % CI 1.35-1.72; P < 0.05; 866 vs 641), fractures (OR 1.33, 95 % CI 1.18-1.50; P < 0.05; 596 vs 438), arthralgia (OR 1.27, 95 % CI 1.19-1.36; P < 0.05; 2404 vs 2060), myalgia (OR 1.29, 95 % CI 1.16-1.43; P < 0.05; 960 vs 776), and hot flashes (OR 1.40, 95 % CI 1.15-1.69; P < 0.05; 2418 vs 2174) and was associated with opposite risk of vaginal bleeding (OR 0.74, 95 % CI 0.59-0.92; P < 0.05; 148 vs 197). However, the extended therapy did not increase the risk of hypertension (OR 1.03, 95 % CI 0.80-1.33; P = 0.80; 364 vs 353), hypercholesterolemia (OR 1.03, 95 % CI 0.91-1.16; P = 0.62; 643 vs 627), vaginal dryness (OR 1.19, 95 % CI 1.00-1.42; P = 0.05; 294 vs 257), fatigue (OR 1.20, 95 % CI 0.96-1.50; P = 0.12; 1501 vs 1462), dizziness (OR 1.04, 95 % CI 0.92-1.17; P = 0.55; 614 vs 595), headaches (OR 1.06, 95 % CI 0.95-1.18; P = 0.30; 885 vs 848), constipation (OR 0.91, 95 % CI 0.79-1.04; P = 0.15; 480 vs 522), nausea (OR 1.83, 95 % CI 0.49-6.83; P =0.37; 340 vs 325), and dyspnea (OR 0.96, 95 % CI 0.82-1.13; P = 0.64; 340 vs 351). The risk of grade ≥ 3 hot flashes increased following extended endocrine therapy (OR 2.01, 95 % CI 1.23-3.29; P < 0.05; 47 vs 23). We observed no evidence for a difference in the risk of grade ≥3 fatigue, arthralgia, myalgia, bone pain, osteoporosis, fractures, hypertension, and headache between both endocrine therapies. Secondary outcomes shows that after receive EET with AIs, patients can benefit from the control of the local recurrence, distant recurrence, contralateral breast cancer, and second cancers. CONCLUSIONS: Compared with NEET, EET with AIs significantly increased the risk of cardiotoxicity, bone pain, osteoporosis, fractures, hot flashes, arthralgia, myalgia, and grade ≥3 hot flashes, and EET with AIs can reduced the risks of local recurrence, distant recurrence, contralateral breast cancer, and second cancers. These findings offer an important guide for clinicians and patients.


Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Pós-Menopausa , Tamoxifeno/uso terapêutico
6.
Zhonghua Zhong Liu Za Zhi ; 42(7): 586-589, 2020 Jul 23.
Artigo em Chinês | MEDLINE | ID: mdl-32842448

RESUMO

Objective: To explore whether the addition of ovarian function suppression in endocrine therapy of Chinese breast cancer patients under 35 years old will affect the psychological state. Methods: This cross-sectional study enrolled 91 Chinese postoperative breast cancer patients aged 35 years or younger. The depression and anxiety state of patients were assessed by Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7), and their sociodemographic characteristics were collected. Results: Among the 91 patients, 61 were receiving ovarian function suppression (OFS) treatment, 30 were not. Among the 30 patients with out OFS treatment, 2 had PHQ-9 score ≥8, 28 had PHQ-9 score < 8, 1 had GAD-7 score ≥10, and 29 had GAD-7 score < 10. Among the 61 patients with OFS, 19 had PHQ-9 score ≥8, 42 had PHQ-9 score < 8, 8 had GAD-7 score ≥10, and 53 had GAD-7 score <10. The incidence of depression was 6.7% and 31.1% in the non-OFS group and OFS group, respectively (P=0.018). The incidence of anxiety in the two groups was 3.3% and 13.1%, respectively (P=0.174). Univariate analysis showed that the incidence of depression was significantly higher in patients with OFS (P=0.018). After taking into account the sociodemographic factors, pathological stage and treatment of the patients, multivariate analysis showed that the administration of OFS was still significantly related to the incidence of depression (OR=9.14, 95% CI=1.52~55.16, P=0.016). There was no significant difference in the incidence of anxiety (P=0.174). Conclusions: For Chinese young breast cancer patients under 35 years old, the use of OFS in the adjuvant endocrine therapy may lead to a significant increase in the incidence of depression. We should pay attention to the evaluation and monitoring of the psychological state of this population.


Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Depressão , Adulto , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , China/epidemiologia , Estudos Transversais , Depressão/complicações , Feminino , Humanos , Ovário/efeitos dos fármacos , Pré-Menopausa
7.
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
8.
Eur J Cancer ; 136: 1-3, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32610172
9.
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
10.
Medicine (Baltimore) ; 99(24): e20567, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541483

RESUMO

BACKGROUND: Breast cancer is common among women throughout the world and endocrine therapy is an established part of its treatment. But, unfortunately, this has also resulted in intolerable side effects affecting the quality of life. Acupuncture has been widely used to treat endocrine-related side effects in patients with breast cancer, but how long its effect can be maintained has not been published. The systematic review is designed to evaluate the maintenance efficacy of acupuncture for related side effects after breast cancer endocrine therapy. METHODS AND ANALYSIS: We will search for the following databases: PubMed, Embase, Cochrane Library, Web of Science, including China National Knowledge Infrastructure (CNKI), WanFang Data, Technology Periodical Database (VIP), and China Biology Medicine (CBM) from inception to May 2020. Two reviewers will search these databases, collect all articles, and assess the quality of studies separately, and there will be no limitations on language. The primary outcomes will be assessed using acupuncture for endocrine-related hot flashes and joint pain duration (1 month, 3 months, 6 months). Measurement tools include the Kupperman index, Brief Pain Inventory Short Form (BPI-SF), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Brief Pain Inventory-Short (BPI-SF). We will use RevMan V.5.3 for meta-analysis and employ the Grading of Recommendations Assessment, Development and Evaluation System to assess the quality of evidence. RESULTS: This systematic review will evaluate the maintenance efficacy of acupuncture on the side effects of breast cancer endocrine therapy. CONCLUSION: This study will provide high-quality current evidence of how long its effect can be maintained after acupuncture for related side effects after breast cancer endocrine therapy. ETHICS AND DISSEMINATION: Ethical committee approval is not required for this systematic review as patient data will not be collected. This study will help to inform doctors and researchers on the duration of acupuncture treatment for endocrine-related hot flashes and joint pain. The results will be published in a peer-reviewed journal and will be disseminated in relevant conferences. INPLASY REGISTRATION NUMBER: INPLASY202040024.


Assuntos
Terapia por Acupuntura , Antineoplásicos Hormonais/efeitos adversos , Artralgia/terapia , Neoplasias da Mama/tratamento farmacológico , Fogachos/terapia , Artralgia/induzido quimicamente , Fogachos/induzido quimicamente , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
11.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188383, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32535158

RESUMO

Androgen deprivation therapy (ADT) is the primary systemic therapy for treating locally advanced or metastatic prostate cancer (PCa). Despite its positive effect on PCa patient survival, ADT causes various adverse effects, including increased cardiovascular risk factors and cardiotoxicity. Lifespans extension, early use of ADT, and second-line treatment with next-generation androgen receptor pathway inhibitors would further extend the duration of ADT and possibly increase the risk of ADT-induced cardiotoxicity. Meanwhile, information on the molecular mechanisms underlying ADT-induced cardiotoxicity and measures to prevent it is limited, mainly due to the lack of specifically designed preclinical studies and clinical trials. This review article compiles up-to-date evidence obtained from observational studies and clinical trials, in order to gain new insights for deciphering the association between ADT use and cardiotoxicity. In addition, potential cardioprotective strategies involving GnRH receptors and second messenger cGMP are discussed.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/administração & dosagem , Androgênios/metabolismo , Antineoplásicos Hormonais/administração & dosagem , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , GMP Cíclico/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Longevidade/fisiologia , Masculino , Estudos Observacionais como Assunto , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Receptores LHRH/agonistas , Receptores LHRH/antagonistas & inibidores , Receptores LHRH/metabolismo , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento
12.
N Engl J Med ; 382(23): 2187-2196, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32469183

RESUMO

BACKGROUND: Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known. METHODS: In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients. RESULTS: A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88). CONCLUSIONS: In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Leuprolida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Pirimidinonas/uso terapêutico , Testosterona/sangue , Adenocarcinoma/sangue , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Injeções Subcutâneas , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Neoplasias da Próstata/sangue , Pirimidinonas/efeitos adversos
13.
J Cancer Res Clin Oncol ; 146(7): 1791-1800, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32405744

RESUMO

AIM: To assess the impact of age, comorbidities and endocrine therapy (ET) in older breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT). METHODS: From June 2009 to December 2017, we enrolled in this study 735 ER-positive BC patients (stage pT1-T2, pNx-1, M0 and age ≥ 65 years) receiving hypo-RT and followed them until September 2019. Baseline comorbidities included in the hypertension-augmented Charlson Comorbidity Index were retrospectively retrieved. Logistic regression model estimated adjusted-odds ratios (ORs) of ET prescription in relation to baseline patient and tumor characteristics. Competing risk analysis estimated 5-year cumulative incidence function (CIF) of ET discontinuation due to side effects (with BC progression or death as competing events), and its effect on locoregional recurrence (LRR) and distant metastasis (DM) (with death as competing event). RESULTS: ET has been prescribed in 89% patients. In multivariable analysis, the odds of ET prescription was significantly reduced in older patients (≥ 80 years, OR 0.08, 95% CI 0.03-0.20) and significantly increased in patients with moderate comorbidity. Patients ≥ 80 years discontinued the prescribed therapy earlier and more frequently than younger (65-69 years) patients (p = 0.060). Five-year CIF of LLR, DM and death from causes other that BC were 1.7%, 2.2% and 7.5%, respectively. Patients who discontinued ET had higher chance of LRR (p = 0.004). ET use did not impact on OS in any of the analyzed groups. CONCLUSIONS: In older patients, ET did not show a benefit in terms of overall survival. Further studies focusing on tailored treatment approaches are warranted to offer the best care in terms of adjuvant treatment to these patients.


Assuntos
Neoplasias da Mama/epidemiologia , Avaliação Geriátrica , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Terapia Combinada , Comorbidade , Feminino , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Cooperação do Paciente , Prognóstico , Hipofracionamento da Dose de Radiação , Radioterapia Adjuvante , Recidiva , Resultado do Tratamento
14.
Health Qual Life Outcomes ; 18(1): 134, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398097

RESUMO

INTRODUCTION: Breast cancer is one of the most important health problems in the world. In recent years, this cancer has achieved a reduction in mortality, which is attributed to the introduction of mass screening and greater efficacy of post-operative treatment. Many patients with breast cancer have indications only for palliative therapy, but the impact of these methods on the quality of life of patients remains a subject of controversy. It remains unknown whether the progress in improving the quality of life in clinical trials also applies to patients treated as part of daily clinical practice. Data on the results of the impact of conducted therapies on the quality of life outside of clinical trials are scarce. METHODS: The results of palliative chemotherapy and first-line hormonotherapy in 351 patients with advanced, metastatic breast cancer treated in the period from January 2010 to December 2016 in two centres were analysed. RESULTS: The average age of patients was 62 ± 9.8 years; 139 patients received chemotherapy, 91 - therapy containing trastuzumab, and 121 - hormone therapy. A partial response was obtained in 111 patients (32%), stabilization in 150 (43%), and in 90 patients (26%) progression. Median survival time in the whole group of patients was 36 months. Chemotherapy compared to trastuzumab and hormonotherapy was associated with greater total toxicity (p = 0.03). There was a significant relationship between the type of therapy (hormonotherapy, chemotherapy, targeted therapy) and the general average quality of women's life measured with the EORC-QLQ-C30 questionnaire. In addition, a statistically significant difference was found in some somatic complaints (the scale of QLQ-BR23 symptoms) depending on the type of therapy performed. The lowest intensity of complaints was reported by patients during hormonotherapy, then during targeted therapy, and the largest during chemotherapy. CONCLUSIONS: There is no effect of chemotherapy on the overall quality of life. Hormone therapy and trastuzumab therapy improved the quality of life of the treated patients in clinical practice.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
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.
Artigo em Inglês | MEDLINE | ID: mdl-32344759

RESUMO

Breast cancer survivors need to undergo adjuvant endocrine therapy after completion of curative treatments to prevent disease recurrence. These individuals often experience symptoms which are detrimental to their quality of life (QOL). Implementation of interventions for effective symptom management among these survivors is warranted. This review provides an overview of studies on the effectiveness of the previously developed interventions for breast cancer survivors undergoing adjuvant endocrine therapy on symptom alleviation and enhancement of QOL or health-related QOL (HRQOL). Five electronic databases were employed in the literature search. Study selection, data extraction and critical appraisal of the included studies were conducted by three authors independently. Twenty-four studies were included. Both pharmacological and non-pharmacological interventions are effective in addressing the symptoms associated with adjuvant endocrine therapy among the breast cancer survivors, and in improving their QOL, although discrepancies were noted between the studies in terms of the significance of these effects. Pharmacological and non-pharmacological interventions can be effective for symptom management among breast cancer survivors. Their implementation is recommended for effective survivorship care for these individuals. Further research on intervention development for breast cancer survivors is recommended to provide further evidence for the utility of the explored interventions in survivorship care for these patients.


Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Sobreviventes de Câncer , Qualidade de Vida , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Feminino , Humanos , Recidiva Local de Neoplasia , Sobreviventes
17.
Acta Obstet Gynecol Scand ; 99(10): 1297-1302, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32282928

RESUMO

INTRODUCTION: Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. MATERIAL AND METHODS: Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. RESULTS: Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [3 H]thymidine in cultured granulosa cells. CONCLUSIONS: Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Mitotano/efeitos adversos , Cistos Ovarianos/induzido quimicamente , Adulto , Amenorreia/induzido quimicamente , Antineoplásicos Hormonais/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Mitotano/administração & dosagem , Cistos Ovarianos/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto Jovem
19.
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
20.
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
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