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3.
Maturitas ; 138: 58-61, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32631589

RESUMO

OBJECTIVES: To report the effects on the urinary function of ospemifene prescribed for vulvovaginal atrophy (VVA) in patients with overactive bladder (OAB) symptoms refractory to the first line of pharmacologic treatment with antimuscarinic or ß3-agonists drugs. We also try to identify any predictors of response to the ospemifene treatment. STUDY DESIGN: Twenty-five patients with OAB confirmed by detrusor overactivity at urodynamics, refractory to first-line therapy for OAB, were enrolled for the study. All of them received ospemifene 60 mg for 12 weeks because of concomitant VVA. We performed a clinical examination, a 3-day voiding diary, ultrasound examination of bladder wall thickness (BWT), and evaluation by Visual Analogic Scale (VAS) of vaginal dryness at baseline and at 12 weeks. We evaluated urinary symptoms and their impact on the quality of life with UDI-6 SF and OAB-Q (Qol, sf) questionnaires. RESULTS: After 12 weeks of treatment, we observed a significant reduction in the daily (24 h) numbers of episodes of micturition, of nocturia, of urgency and of incontinence. We also found a significant reduction in BWT and vaginal dryness, together with an improvement of OAB-Q and UDI6 SF scores. Among patients who subjectively benefited from the treatment, we found a baseline lower prevalence of constipation and a higher degree of vaginal dryness. CONCLUSIONS: Ospemifene might be a useful option for postmenopausal women with VVA and OAB symptoms, refractory to the first line of treatment with ß3-agonists or antimuscarinic drugs, before considering invasive options.


Assuntos
Tamoxifeno/análogos & derivados , Bexiga Urinária Hiperativa/tratamento farmacológico , Doenças Vaginais/tratamento farmacológico , Idoso , Atrofia/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Bexiga Urinária Hiperativa/fisiopatologia , Urodinâmica , Vagina/patologia , Doenças Vaginais/fisiopatologia
4.
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
5.
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
6.
Medicine (Baltimore) ; 99(22): e20423, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481440

RESUMO

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is the most common cause of motor neuron disease, and effective treatment for ALS is still lacking. Transactive response (TAR) -DNA-binding protein-43 (TDP-43) is aggregated in the neurons of ALS patients. Animal studies shown TDP-43 aggregation can be attenuated by enhancing autophagy by tamoxifen. However, its beneficial effects for ALS patients remain unknown. METHODS: Eighteen patients with ALS without mutations in superoxide dismutase-1 (SOD-1) or fused in sarcoma (FUS) genes were randomly assigned into the tamoxifen 40 mg/day or placebo group in a double-blinded manner and all were given riluzole twice daily. Participants were followed up at 1, 3, 6, and 12 months. The primary end point was time to death or dependence on mechanical ventilation. Secondary end points were decline of the revised ALS Functional Rating Scale (ALSFRS-R) score and pulmonary function measured by forced vital capacity (FVC). RESULTS: Ten participants were randomly assigned in the treatment group with tamoxifen, 7 finished trial, 1 reach primary endpoint; while 8 participants in the placebo group, 2 finished trial and 2 reach primary end point. The proportion of participants reaching the primary end point was lower in the tamoxifen group but did not reach statistical significance. At the 1-, 3-, and 6-month follow-up, the average decline rates of the ALSFRS-R score were slower in the tamoxifen group. No significant difference was observed in FVC and ALSFRS-R score at 12 months between groups. CONCLUSION: Tamoxifen exerted only a modest effect on attenuate progression for 6 months in this small trial. Additional larger scale studies should be necessary to confirm whether enhancing autophagy can attenuate ALS progression.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Esclerose Amiotrófica Lateral/genética , Autofagia/efeitos dos fármacos , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
7.
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
8.
Artigo em Inglês | MEDLINE | ID: mdl-32570717

RESUMO

In this study, an in-depth analysis of weight management experiences of breast cancer patients treated with tamoxifen is conducted, thereby providing basic data to help develop a multidimensional strategy to reduce recurrence and increase the survival rate of breast cancer patients. Study participants included nine breast cancer patients who were treated with tamoxifen at Kosin University Hospital and Saegyero Hospital in Busan Metropolitan City, Korea. This study employed the photovoice methodology. Participants described the need for family support and cooperation with weight management, provision of personalized weight management programs by medical institutions, provision of information on weight management programs by the community, and financial support for the weight management programs for breast cancer patients at the national level. This study emphasized the importance of weight management for breast cancer patients treated with tamoxifen and collected and analyzed vivid opinions of these patients using photos taken by them.


Assuntos
Antineoplásicos Hormonais , Peso Corporal , Neoplasias da Mama , Tamoxifeno , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , República da Coreia , Tamoxifeno/uso terapêutico
9.
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
10.
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
11.
J Cancer Res Clin Oncol ; 146(6): 1395-1404, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32270286

RESUMO

PURPOSE: To review recent pharmacogenomics studies on breast cancer patients undergoing tamoxifen therapy, highlighting how our knowledge on cytochrome P450 2D6 (CYP2D6) can help to guide the development of adjuvant therapies for these patients. METHODS: A comprehensive literature search was conducted. Articles reporting findings pertaining to the effect of CYP2D6 on the therapeutic efficacy of tamoxifen, those reporting how targeting CYP2D6 could inform tamoxifen-based therapy development, and those on the tamoxifen effects on cell lines and animal models were included in the review. RESULTS: With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Our review indicates the potential effectiveness of targeting these SNPs, including those for the CYP2D6*10 allele (c. 100C > T), in modifying the level of tamoxifen metabolism. These findings suggest the importance of pharmacogenomics research in our understanding of the efficacy of adjuvant therapies. However, the involvement of multiple enzymes in tamoxifen metabolism, dietary factors, ethnic differences in gene frequencies, and patients' compliance to tamoxifen therapies in studies do present challenges in pharmacogenomics research. CONCLUSIONS: Pharmacogenomics could play important roles in mediating the advancement of tamoxifen-based adjuvant therapies. Research efforts should be directed towards the exploration of further SNPs of CYP2D6 that affect tamoxifen metabolism, as well as epigenetic changes in CYP2D6, enabling the design of precision medicine and confirming clinical validity in the use of pharmacogenomics for tamoxifen.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Citocromo P-450 CYP2D6/genética , Farmacogenética , Tamoxifeno/uso terapêutico , Animais , Neoplasias da Mama/enzimologia , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
12.
PLoS One ; 15(4): e0231786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302351

RESUMO

BACKGROUND: G protein-coupled estrogen receptor (GPER), or G protein-coupled receptor 30 (GPR30), is reported to mediate non-genomic estrogen signaling. GPR30 associates with breast cancer (BC) outcome and may contribute to tamoxifen resistance. We investigated the expression and prognostic significance of GPR30 in metachronous contralateral breast cancer (CBC) as a model of tamoxifen resistance. METHODS: Total GPR30 expression (GPR30TOT) and plasma membrane-localized GPR30 expression (GPR30PM) were analyzed by immunohistochemistry in primary (BC1; nBC1 = 559) and contralateral BC (BC2; nBC2 = 595), and in lymph node metastases (LGL; nLGL1 = 213; nLGL2 = 196). Death from BC (BCD), including BC death or death after documented distant metastasis, was used as primary end-point. RESULTS: GPR30PM in BC2 and LGL2 were associated with increased risk of BCD (HRBC2 = 1.7, p = 0.03; HRLGL2 = 2.0; p = 0.02). In BC1 and BC2, GPR30PM associated with estrogen receptor (ER)-negativity (pBC1<0.0001; pBC2<0.0001) and progesterone receptor (PR)-negativity (pBC1 = 0.0007; pBC2<0.0001). The highest GPR30TOT and GPR30PM were observed in triple-negative BC. GPR30PM associated with high Ki67 staining in BC1 (p<0.0001) and BC2 (p<0.0001). GPR30TOT in BC2 did not associate with tamoxifen treatment for BC1. However, BC2 that were diagnosed during tamoxifen treatment were more likely to express GPR30PM than BC2 diagnosed after treatment completion (p = 0.01). Furthermore, a trend was observed that patients with GPR30PM in an ER-positive BC2 had greater benefit from tamoxifen treatment. CONCLUSION: PM-localized GPR30 staining is associated with increased risk of BC death when expressed in BC2 and LGL2. Additionally, PM-localized GPR30 correlates with prognostic markers of worse outcome, such as high Ki67 and a triple-negative subtype. Therefore, PM-localized GPR30 may be an interesting new target for therapeutic exploitation. We found no clear evidence that total GPR30 expression is affected by tamoxifen exposure during development of metachronous CBC, or that GPR30 contributes to tamoxifen resistance.


Assuntos
Neoplasias da Mama/metabolismo , Membrana Celular/metabolismo , Segunda Neoplasia Primária/metabolismo , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Células HeLa , Humanos , Incidência , Células MCF-7 , Pessoa de Meia-Idade , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Prognóstico , Fatores de Risco , Tamoxifeno/uso terapêutico , Resultado do Tratamento
13.
Cochrane Database Syst Rev ; 3: CD013538, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32141074

RESUMO

BACKGROUND: Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone receptor-positive breast cancer and in premenopausal women includes oestrogen receptor blockade with tamoxifen, temporary suppression of ovarian oestrogen synthesis by luteinising hormone releasing hormone (LHRH) agonists, and permanent interruption of ovarian oestrogen synthesis with oophorectomy or radiotherapy. Recent international consensus statements recommend single-agent tamoxifen or aromatase inhibitors with ovarian function suppression (OFS) as the current standard adjuvant endocrine therapy for premenopausal women (often preceded by chemotherapy). This review examined the role of adding OFS to another treatment (i.e. chemotherapy, endocrine therapy, or both) or comparing OFS to no further adjuvant treatment. OBJECTIVES: To assess effects of OFS for treatment of premenopausal women with hormone receptor-positive early breast cancer. SEARCH METHODS: For this review update, we searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov on 26 September 2019. We screened the reference lists of related articles, contacted trial authors, and applied no language restrictions. SELECTION CRITERIA: We included all randomised trials assessing any method of OFS, that is, oophorectomy, radiation-induced ovarian ablation, or LHRH agonists, as adjuvant treatment for premenopausal women with early-stage breast cancer. We included studies that compared (1) OFS versus observation, (2) OFS + chemotherapy versus chemotherapy, (3) OFS + tamoxifen versus tamoxifen, and (4) OFS + chemotherapy + tamoxifen versus chemotherapy + tamoxifen. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and meta-analysis was performed using a fixed-effect model. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). Toxicity, contralateral breast cancer, and second malignancy were represented as risk ratios (RRs), and quality of life data were extracted when provided. MAIN RESULTS: This review update included 15 studies involving 11,538 premenopausal women with hormone receptor-positive early breast cancer; these studies were conducted from 1978 to 2014. Some of these treatments are not current standard of care, and early studies did not assess HER2 receptor status. Studies tested OFS versus observation (one study), OFS plus chemotherapy versus chemotherapy (six studies), OFS plus tamoxifen versus tamoxifen (six studies), and OFS plus chemotherapy and tamoxifen versus chemotherapy and tamoxifen (two studies). Of those studies that reported the chemotherapy regimen, an estimated 72% of women received an anthracycline. The results described below relate to the overall comparison of OFS versus no OFS. High-certainty evidence shows that adding OFS to treatment resulted in a reduction in mortality (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.78 to 0.94; 11 studies; 10,374 women; 1933 reported events). This treatment effect was seen when OFS was added to observation, to tamoxifen, or to chemotherapy and tamoxifen. The effect on mortality was not observed when OFS was added to chemotherapy without tamoxifen therapy (HR 0.95, 95% CI 0.82 to 1.09; 5 studies; 3087 women; median follow-up: range 7.7 to 12.1 years). The addition of OFS resulted in improved DFS (HR 0.83, 95% CI 0.77 to 0.90; 10 studies; 8899 women; 2757 reported events; high-certainty evidence). The DFS treatment effect persisted when OFS was added to observation, to tamoxifen, and to chemotherapy and tamoxifen. The effect on DFS was reduced when OFS was added to chemotherapy without tamoxifen therapy (HR 0.90, 95% CI 0.79 to 1.01; 5 studies; 2450 women). Heterogeneity was low to moderate across studies for DFS and OS (respectively). Evidence suggests that adding OFS slightly increases the incidence of hot flushes (grade 3/4 or any grade; risk ratio (RR) 1.60, 95% CI 1.41 to 1.82; 6 studies; 5581 women; low-certainty evidence, as this may have been under-reported in these studies). Two other studies that could not be included in the meta-analysis reported a higher number of hot flushes in the OFS group than in the no-OFS group. Seven studies involving 5354 women collected information related to mood; however this information was reported as grade 3 or 4 depression, anxiety, or neuropsychiatric symptoms, or symptoms were reported without the grade. Two studies reported an increase in depression, anxiety, and neuropsychiatric symptoms in the OFS group compared to the no-OFS group, and five studies indicated an increase in anxiety in both treatment groups (but no difference between groups) or no difference overall in symptoms over time or between treatment groups. A single study reported bone health as osteoporosis (defined as T score < -2.5); this limited evidence suggests that OFS increases the risk of osteoporosis compared to no-OFS at median follow-up of 5.6 years (RR 1.16, 95% CI 1.10 to 28.82; 2011 women; low-certainty evidence). Adding OFS to treatment likely reduces the risk of contralateral breast cancer (HR 0.75, 95% CI 0.57 to 0.97; 9 studies; 9138 women; moderate-certainty evidence). Quality of life was assessed in five studies; four studies used validated tools, and the fifth study provided no information on how data were collected. Two studies reported worse quality of life indicators (i.e. vaginal dryness, day and night sweats) for women receiving OFS compared to those in the no-OFS group. The other two studies indicated worsening of symptoms (e.g. vasomotor, gynaecological, vaginal dryness, decline in sexual interest, bone and joint pain, weight gain); however these side effects were reported in both OFS and no-OFS groups. The study that did not use a validated quality of life tool described no considerable differences between groups. AUTHORS' CONCLUSIONS: This review found evidence that supports adding OFS for premenopausal women with early, hormone receptor-positive breast cancers. The benefit of OFS persisted when compared to observation, and when added to endocrine therapy (tamoxifen) or chemotherapy and endocrine therapy (tamoxifen). The decision to use OFS may depend on the overall risk assessment based on tumour and patient characteristics, and may follow consideration of all side effects that occur with the addition of OFS.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Hormônio Liberador de Gonadotropina/agonistas , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Feminino , Humanos , Pré-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Resultado do Tratamento
14.
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
15.
Rev. osteoporos. metab. miner. (Internet) ; 12(1): 7-13, ene.-mar. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-192304

RESUMO

OBJETIVO: Los inhibidores de la aromatasa (IA) se han asociado con una pérdida de masa ósea acelerada y un mayor riesgo de fracturas osteoporóticas. Con este trabajo se pretendió evaluar los factores de riesgo de fractura incidente en pacientes con cáncer de mama que reciben IA. MATERIAL Y MÉTODOS: Estudio prospectivo-observacional de cohorte de mujeres con cáncer de mama que inician tratamiento con IA (cohorte B-ABLE). Las pacientes realizaron tratamiento durante 5 años o bien 2 ó 3 años si habían recibido previamente tamoxifeno. Se les evaluó la salud ósea desde el inicio del tratamiento hasta un año después de finalizar dicho tratamiento mediante densitometría ósea, marcadores de remodelado óseo, niveles de vitamina D y una radiografía antero-posterior y otra lateral de columna. Se realizó el cálculo de riesgo de fractura mediante la herramienta FRAX® antes de iniciar IA. Se utilizaron modelos de Cox para calcular los ratios de riesgo (HR [IC 95%]) de fractura. RESULTADOS: Un total de 943 pacientes fueron incluidas en el estudio. El 5,4% sufrieron una fractura incidente, la mayoría durante el tratamiento con IA, aunque un 21,5% ocurrieron durante el primer año después de finalizar la terapia. La mayoría de las fracturas incidentes fueron vertebrales clínicas (29,4%) y de Colles (31,4%). El 86,3% de las pacientes tenían un diagnóstico de osteopenia u osteoporosis en el momento de la fractura y el 33% tenían los niveles de β-CTX (isómero β del telopéptido carboxiterminal del colágeno tipo I) por encima de la normalidad. Las pacientes diagnosticadas de osteoporosis o con riesgo de fractura al inicio del estudio fueron tratadas con antirresortivos óseos. No se encontraron diferencias significativas en el riesgo de fractura entre pacientes con y sin tratamiento antirresortivo: HR=1,75 [IC 95%: 0,88 a 3,46]. Tampoco se encontraron diferencias entre las pacientes que habían hecho tratamiento previo con tamoxifeno respecto a las que no (HR=1,00 [IC 95%: 0,39 a 2,56]). La herramienta FRAX® dio valores de media dentro del rango de riesgo intermedio, con 13 pacientes con valores de alto riesgo de fractura principal. CONCLUSIONES: El principal factor de riesgo detectado para fractura incidente en pacientes tratadas con IA es el diagnóstico de osteopenia u osteoporosis. El cálculo de la herramienta FRAX® y la determinación de los niveles de β-CTX son herramientas útiles para identificar a pacientes de alto riesgo


OBJETIVO:Aromatase inhibitors (AI) have been associated with an accelerated loss of bone mass and an increased risk ofosteoporosis fractures. This study assesses the risk factors for incident fracture in breast cancer patients receiving AI. MATERIAL AND METHODS:Prospective‐observational cohort study of women with breast cancer who begin treatment withAI (B‐ABLE cohort). Patients were treated for 5 years or 2 or 3 years if they had previously received tamoxifen. Bone healthwas assessed from the beginning of the treatment until one year post treatment by bone densitometry, bone remodelingmarkers, vitamin D levels and an anteroposterior and lateral spine radiography. The fracture risk calculation was performedusing the FRAX® tool before starting AI. Cox models were used to calculate the risk ratios (HR [95% CI]) of fracture. RESULTS: A total of 943 patients were included in the study.5.4% suffered an incident fracture, most during AI treatment,although 21.5% occurred during the first year after the end of therapy. Most of the incident fractures were clinical vertebral (29.4%) and Colles (31.4%).86.3% of the patients had a diagnosis of osteopenia or osteoporosis at the time of the fractureand 33% had the levels of β‐CTX (β isomer of the carboxyterminal telopeptide of type I collagen) above normal. Patients diagnosed with osteoporosis or at risk of fracture at the start of the study were treated with bone antiresorptives. No significant differences in fracture risk were found between patients with and without antiresorptive therapy: HR=1.75[95% CI: 0.88 to 3.46]. Nor were differences found among patients who had previously treated with tamoxifen comparedto those who did not (HR=1.00 [95% CI 0.39 to 2.56]). The FRAX®tool gave average values within the intermediate riskrange, with 13 patients with high risk of major fracture values. CONCLUSIONS:The main risk factor detected for incident fracture in patients treated with AI is the diagnosis of osteopeniaor osteoporosis. The calculation of the FRAX® tool and the determination of β‐CTX levels are useful tools to identifyhigh‐risk patients


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/tratamento farmacológico , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Índice de Massa Corporal , Fraturas por Osteoporose/induzido quimicamente , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Fatores de Risco , Estudos Prospectivos , Estudos de Coortes , Incidência
16.
Cancer Sci ; 111(5): 1840-1850, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32086991

RESUMO

Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.


Assuntos
Anticorpos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Claudina-4/imunologia , Animais , Anticorpos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Claudina-1 , Claudina-4/química , Claudina-4/genética , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Medicine (Baltimore) ; 99(8): e19083, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080081

RESUMO

BACKGROUND: Breast cancer is the most prevalent cancer in females and disease recurrence remains a significant problem. To prevent recurrence, tamoxifen is prescribed for at least 5 years. However, among patients who receive tamoxifen, individual responses are highly variable. These responses are affected by the type, frequency, and severity of endocrine symptoms, as well as adherence rates. Polymorphisms in genes involved in the metabolism of tamoxifen (ie, CYP3A4, CYP2D6) may influence responses to tamoxifen. In this study, the inter-relationships among endocrine symptoms, drug adherence, and genetic polymorphisms in Chinese breast cancer patients receiving tamoxifen therapy will be examined. We hypothesize that patients with more severe endocrine symptoms will be less likely to adhere to tamoxifen treatment. In addition, we hypothesize that a relationship will exist between the severity of tamoxifen-induced symptoms and allelic variations in tamoxifen metabolism-related genes. Although many association studies have determined that select genotypes influence the efficacy of tamoxifen, very few studies have investigated for associations between tamoxifen-induced endocrine symptoms and these polymorphisms. OBJECTIVES: The aim of this study was to characterize genetic polymorphisms in tamoxifen metabolism-associated genes in Chinese women with breast cancer and to explore the inter-relationships between genetic polymorphisms, endocrine symptoms, and adherence to tamoxifen. METHOD: We will conduct a prospective cohort study that follows 200 Chinese women over 18 months and assess treatment-related symptoms and genetic variations. Endocrine symptoms and drug adherence will be determined through interview-administered standardized questionnaires. Polymorphisms in drug metabolism genes will be determined using real-time polymerase chain reaction based genotyping method. Data will be analyzed to determine associations between allelic variations, endocrine symptoms, and adherence. DISCUSSION: The proposed study will evaluate for polymorphisms in gene(s) that are associated with tamoxifen-related endocrine symptoms and adherence with tamoxifen. We will explore the relationships between genotypes, endocrine symptoms, and drug adherence in Chinese breast cancer patients. Findings from this study may assist clinicians to identify patients at higher risk for a worse symptom experience and lower adherence rates and enable them to initiate appropriate interventions. In the long term, the findings from this study may be used to develop and test tailored symptom management interventions for these patients.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Doenças do Sistema Endócrino/induzido quimicamente , Tamoxifeno/efeitos adversos , Alelos , Antineoplásicos Hormonais/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/epidemiologia , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Cooperação do Paciente , Polimorfismo de Nucleotídeo Único , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença , Tamoxifeno/metabolismo , Tamoxifeno/uso terapêutico
18.
Medicine (Baltimore) ; 99(2): e18550, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914031

RESUMO

BACKGROUND: Adjuvant endocrine therapy is a vital portion of postoperative comprehensive treatment for breast cancer patients. In recent years, studies have shown that endocrine therapy has a certain impact on the serum lipids of breast cancer patients, and the changes of lipid profiles may bring a series of problems. However, very few studies focus on this issue to date. The results of these studies are inconsistent, and the influence of different adjuvant endocrine modalities on lipid profiles still remains controversial. In order to better explore this issue, we conduct this network meta-analysis. METHOD: The protocol followed preferred reporting items for systematic reviews and meta-analyses protocols. Three main databases (PubMed, Embase, and the Cochrane Library) will be searched systematically for eligible randomized controlled trials without language restriction. In addition, a manual search of the references of relevant published studies will also be considered. Two reviewers will conduct studies selection, data extraction, and risk of bias assessment independently. The primary outcome is the variation of biochemical parameters - the serum lipid profiles (cholesterol, triglyceride, high-density lipoprotein, low low-density lipoprotein). RESULTS: The results will provide useful information about the side effects of different adjuvant endocrine drugs on lipid profiles in postoperative breast cancer patients (estrogen receptor-positive and/or progesterone receptor-positive). CONCLUSION: The findings of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019129850.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Lipídeos/sangue , Anastrozol/farmacologia , Anastrozol/uso terapêutico , Androstadienos/farmacologia , Androstadienos/uso terapêutico , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , Quimioterapia Adjuvante , Humanos , Letrozol/farmacologia , Letrozol/uso terapêutico , Metanálise em Rede , Projetos de Pesquisa , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Toremifeno/farmacologia , Toremifeno/uso terapêutico
19.
Biochim Biophys Acta Rev Cancer ; 1873(1): 188339, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917206

RESUMO

Increasing emphasis has been given to prevention as a feasible approach to reduce the cancer burden. However, for its clinical success, further advances are required to identify effective chemopreventive agents. This review affords a critical and up-to-date discussion of issues related to cancer prevention, including an in-depth knowledge on BRCA1 and p53 tumor suppressor proteins as key molecular players. Indeed, it compiles the most recent advances on the topic, highlighting the unique potential of BRCA1 and p53 germline mutations as molecular biomarkers for risk assessment and targets for chemoprevention. Relevant evidences are herein provided supporting the effectiveness of distinct pharmacological agents in cancer prevention, by targeting BRCA1 and p53. Moreover, the rationale for using germline mutant BRCA1- or p53-related cancer syndromes as model systems to investigate effective chemopreventive agents is also addressed. Altogether, this work provides an innovative conception about the dependence on p53 and BRCA1 co-inactivation in tumor formation and development, emphasizing the relationship between these two proteins as an encouraging direction for future personalized pharmacological interventions in cancer prevention.


Assuntos
Proteína BRCA1/genética , Quimioprevenção/métodos , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/prevenção & controle , Tamoxifeno/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína BRCA1/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Proteína Supressora de Tumor p53/metabolismo
20.
Arch Gynecol Obstet ; 301(2): 565-571, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31900584

RESUMO

PURPOSE: Endocrine therapies using tamoxifen and/or aromatase inhibitors are important therapeutic options for the targeted treatment of hormone-responsive breast cancer. In addition to nuclear estrogen receptors ERα and ß, G-protein-coupled estrogen receptor GPER-1 is a third receptor-mediating estrogen effects in breast cancer cells. The aim of this study was to examine to what extent GPER-1 expression might affect the efficacy of primary endocrine treatment of breast cancer. METHODS: GPER-1 expression was determined in tissue samples from patients with early breast cancer by means of immunohistochemistry and a GPER-1 score of ≥ 3 was considered to be positive. In a total of 165 patients, the response to a primary therapy with tamoxifen (TAM) or aromatase inhibitors (AI) was assessed by ultrasound imaging for up to 6 months. The primary endpoint of this study was the response to treatment evaluated by RECIST 1.1 criteria. RESULTS: GPER-1 expression was observed in 127 (77.0%) out of 165 cases. Based on GPER-1 expression and the type of endocrine treatment, the patients were divided into 4 groups: GPER-1 negative/TAM (12.1%), GPER-1 negative/AI (10.9%), GPER-1 positive/TAM (44.8%), and GPER-1 positive/AI (32.1%). The groups were well balanced regarding different clinical and pathological factors. After 4 and 6 months of treatment, a high level of stable disease or progressive disease was observed in the GPER-1 positive/TAM group only (p < 0.0001), whereas in the other three groups of patients, the most common objective response was classified as partial response. We observed a continuous reduction of mean tumor size in patients treated with aromatase inhibitors irrespective of the GPER-1 status and in GPER-1 negative patients treated with TAM. In contrast, in GPER-1 positive patients treated with TAM, a reduction of mean tumor size was observed only in the first 2 months after beginning of treatment. Four and six months after start of treatment, no reduction, but even a slight increase of tumor size was observed in this patients group. CONCLUSIONS: GPER-1 expression is significantly associated with a reduced effect of primary treatment with tamoxifen in breast cancer patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Tamoxifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade
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