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1.
Medicine (Baltimore) ; 100(33): e26949, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414958

RESUMO

BACKGROUND: Ovarian function suppressor (OFS) plus either tamoxifen (TAM) or aromatase inhibitor (AI) could improve the survival outcome for premenopausal hormone receptor-positive (HR+) breast cancer. However, the optimal OFS-based regimen and medication duration remain uncertain. This article aims to systematically evaluate the OFS-based adjuvant endocrine therapy for premenopausal breast cancer. METHODS: We searched several public databases from January 1980 to November 2020. A random model was adopted in this meta-analysis. We used the hazard ratio (HR) with a 95% confidence interval (CI) for the statistical analysis of efficacy. The primary outcome measures included overall survival and disease-free survival. RESULTS: A total of 32 articles with 37,224 cases were included in this network meta-analysis. OFS+TAM improved 5-year disease-free survival (HR -0.09, 95% CI -0.16 to -0.01) and 5-year overall survival (HR -0.18, 95% CI -0.33 to -0.03) compared with TAM monotherapy. For OFS+AI, although the 5-year disease-free survival was improved (HR -0.18, 95% CI -0.29 to -0.08), the 5-year overall survival was not improved (HR -0.13, 95% CI -0.43 to 0.18). In subgroup analysis, both OFS+AI and OFS+TAM showed a protective effect in stage I-III patients compared with stage I-II patients. For the course of therapy, OFS+TAM for 2-years could achieve clinical benefit and the best course of therapy of OFS+AI still waits for further study. CONCLUSIONS: OFS+TAM might be a better option than OFS+AI for premenopausal intensive adjuvant endocrine therapy. Stage III patients are more suitable for the OFS-based therapy. For the medication duration, the 2-years course of OFS+TAM could be effective. This analysis provides helpful information for selecting therapeutic regimen in intensive adjuvant endocrine therapy and identifying the target population.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Metanálise em Rede , Análise de Sobrevida
2.
Medicine (Baltimore) ; 100(32): e26797, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397882

RESUMO

RATIONALE: Polycystic liver disease is a rare disease characterized by the growth of numerous cysts in the liver. The liver function remains well preserved, but liver volumes can grow very large, and some patients ultimately need a liver transplantation. Other treatment options are limited and there is an unmet need for new therapeutic options. PATIENT CONCERNS: We describe a 59-year-old patient with pain in the abdomen, especially when bending forward. Five years ago, she was diagnosed with breast cancer and as an incidental finding a couple of large liver cysts were diagnosed, explaining her abdominal pain. DIAGNOSIS: Polycystic liver disease with several large liver cysts. INTERVENTIONS: The patient was treated with tamoxifen, an estrogen receptor modulator, as treatment for her hormone receptor positive breast cancer. One of the liver cysts was aspirated. OUTCOMES: In the 4.6 years after the start of tamoxifen treatment, 20 mg once daily, the volume of her liver cysts decreased remarkably. There was a reduction of combined cyst volume from 311 mL to 22 mL without percutaneous drainage. LESSONS: Epidemiological as well as experimental evidence supports a pivotal role for estrogens as a driver for growth of polycystic livers. Estrogen antagonism has often been proposed as a therapeutic target, but supporting evidence is lacking in the literature. We hypothesize that the decrease in cyst size in this patient was caused by tamoxifen therapy, suggesting an in vivo antagonistic effect on cystic cholangiocytes. This is an important finding because tamoxifen could be a promising new treatment option for polycystic liver disease.


Assuntos
Cistos/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Tamoxifeno/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Cistos/diagnóstico , Feminino , Seguimentos , Humanos , Hepatopatias/diagnóstico , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
3.
Health Psychol ; 40(6): 398-407, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34323542

RESUMO

OBJECTIVES: Oral endocrine therapy improves survival among hormone responsive breast cancer (HRBC) survivors; however, 30-70% of patients are nonadherent. One patient-centered factor that may impact adherence is delay discounting (DD), or the degree to which patients value future outcomes. In prior research, DD is robustly associated with maladaptive health behavior; but no work to our knowledge has examined delay discounting and medication nonadherence in breast cancer patients. Study 1 examined cross-sectional associations between DD and endocrine therapy nonadherence. Study 2 examined whether DD in the HRBC population is amenable to a brief intervention-episodic future thinking (EFT), in which participants preexperience future events. METHOD: In Study 1, HRBC survivors completed assessments of DD and endocrine therapy adherence (pill count and self-report). In Study 2, participants were randomized to engage in a brief behavioral intervention (EFT) or a control condition, and again completed assessments of DD. RESULTS: Eighty nine female HRBC survivors completed Studies 1 and 2. Controlling for other known risk factors, greater DD was significantly associated with poorer pill-count but not self-report adherence. In Study 2, the EFT intervention significantly reduced DD when compared to control episodic thinking. CONCLUSIONS: DD is associated with direct-observation (pill count) measures of endocrine therapy adherence in HRBC survivors, suggesting it is a potential therapeutic target for improving adherence. This target is also amenable to intervention with EFT. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Desvalorização pelo Atraso , Adesão à Medicação , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Estudos Transversais , Feminino , Humanos , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos
4.
N Engl J Med ; 385(5): 395-405, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34320285

RESUMO

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


Assuntos
Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Administração Oral , Idoso , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio , Receptores de Progesterona , Tamoxifeno/uso terapêutico
7.
Gan To Kagaku Ryoho ; 48(7): 911-919, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34267028

RESUMO

OBJECTIVE: To investigate the real-world use of primary androgen-deprivation therapy(PADT; gonadotropin-releasing hormone agonists[leuprorelin/goserelin]and antagonists[degarelix]/surgical castration), its clinical effectiveness, and the characteristics of Japanese patients with hormone-sensitive prostate cancer treated with PADT. METHODS: In this retrospective, observational study, patients using PADT(≥1 record)in the 2016-2018 Japan Study Group of Prostate Cancer registry were followed up from their initial date of PADT until October 2018. The primary endpoints included prostate-specific antigen( PSA)response rate(PSA<4 ng/mL)and duration of initial treatment. RESULTS: Of 1,895 patients, 47.7%, 24.4%, and 22.0% received leuprorelin, goserelin, and degarelix, respectively; 5.9% underwent surgical castration. The degarelix group had the highest median PSA at diagnosis(116.7 ng/mL)and proportion of patients with clinical Stage Ⅳ prostate cancer (72.9%)and Gleason score 9-10(59.7%). A concomitant antiandrogen was used in >80% and 70% of patients in the leuprorelin/goserelin and degarelix groups, respectively; bicalutamide was used most commonly(99.0%). Median duration of initial treatment was 20.8 months in the degarelix group and not yet reached in the leuprorelin/goserelin groups; continuation rates at 24 months were 44.6% and 81.6%/87.3%, respectively. The PSA response rate was the highest in the leuprorelin group(93.7%); median percentage change in PSA was comparable across all treatment groups(-99.1% to -99.8%). CONCLUSIONS: Real-world use of PADT in patients with hormone-sensitive prostate cancer is likely based on its specific therapeutic attributes and patient characteristics.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Hormônio Liberador de Gonadotropina , Humanos , Japão , Masculino , Oligopeptídeos , Antígeno Prostático Específico , Neoplasias da Próstata/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
8.
Breast Cancer Res Treat ; 189(2): 317-331, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34282517

RESUMO

PURPOSE: Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The amino acid transporter SLC1A5 has emerging importance as a prognostic marker and potential therapeutic target in various types of cancer. This study aims to investigate its role in luminal breast cancer as a potential predictive marker for endocrine treatment. METHODS: SLC1A5 expression was assessed at the transcriptomic and proteomic levels in large, well-characterized cohorts of luminal breast cancer. The sensitivity to endocrine therapy after SLC1A5 knockdown was investigated in vitro, using MCF7 and MDA-MB-175 cell lines. Bioinformatic analyses were performed to study the interacting networks of SLC1A5 and to identify a key co-expressed gene with SLC1A5. RESULTS: Here, we showed that patients with tumors that highly expressed SLC1A5 associated with a high risk of relapse after endocrine treatment. In vitro, depletion of SLC1A5 increases the sensitivity of luminal breast cancer cells to tamoxifen. TALDO1 was identified as key co-expressed gene with SLC1A5, and in vitro knockdown of SLC1A5 showed reduction in TALDO1 expression. Indeed, TALDO1 was associated with poor clinical outcomes in patients who were subject to endocrine therapy. CONCLUSION: These findings suggest that metabolic alterations, particularly the interaction between the key amino acid transporter SLC1A5 and metabolic enzyme TALDO1, could affect the sensitivity of endocrine therapy. This study demonstrated the prognostic value of both SLC1A5 and TALDO1 as biomarkers in luminal breast cancer.


Assuntos
Sistema ASC de Transporte de Aminoácidos/genética , Neoplasias da Mama , Antígenos de Histocompatibilidade Menor/genética , Receptores de Estrogênio , Transaldolase/genética , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Recidiva Local de Neoplasia , Proteômica , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Tamoxifeno/uso terapêutico
9.
J Cancer Res Clin Oncol ; 147(8): 2337-2347, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34156518

RESUMO

OBJECTIVE: We aimed to review of literature on the clinical presentation, management and outcomes of pituitary apoplexy following gonadotrophic release hormone (GnRH) agonist administration for the treatment of prostate cancer. METHODS: We used PRISMA guidelines for our systematic review and included all English language original articles on pituitary apoplexy following GnRH agonist administration among prostate cancer patients from Jan 1, 1995 to Dec 31, 2020. Data on patient demographics, prostate cancer type, Gleason score at diagnosis, history of pituitary adenoma, clinical presentation, GnRH agonist, interval to pituitary apoplexy, laboratory evaluation at admission, radiologic findings, treatment of pituitary apoplexy, time to surgery if performed, pathology findings, and clinical/hormonal outcomes were collected and analyzed. RESULTS: Twenty-one patients with pituitary apoplexy met our inclusion criteria. The mean age of patients was 70 (60-83) years. Leuprolide was the most common used GnRH agonist, used in 61.9% of patients. Median duration to symptom onset was 5 h (few minutes to 6 months). Headache was reported by all patients followed by ophthalmoplegia (85.7%) and nausea/vomiting (71.4%). Three patients had blindness at presentation. Only 8 cases reported complete anterior pituitary hormone evaluation on presentation and the most common endocrine abnormality was FSH elevation. Tumor size was described only in 15 cases and the mean tumor size was 26.26 mm (18-48 mm). Suprasellar extension was the most common imaging finding seen in 7 patients. 71.4% of patients underwent pituitary surgery, while 23.8% were managed conservatively. Interval between symptoms onset to pituitary surgery was 7 days (1-90 days). Gonadotroph adenoma was most common histopathologic finding. Clinical resolution was comparable, while endocrine outcomes were variable among patients with conservative vs surgical management. CONCLUSION: Although the use of GnRH agonists is relatively safe, it can rarely lead to pituitary apoplexy especially in patients with pre-existing pituitary adenoma. Physicians should be aware of this complication as it can be life threatening. A multidisciplinary team approach is recommended in treating individuals with pituitary apoplexy.


Assuntos
Adenoma/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Hormônio Liberador de Gonadotropina/agonistas , Apoplexia Hipofisária/induzido quimicamente , Neoplasias da Próstata/tratamento farmacológico , Adenoma/epidemiologia , Adenoma/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Apoplexia Hipofisária/diagnóstico , Apoplexia Hipofisária/epidemiologia , Apoplexia Hipofisária/terapia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia
11.
Nutrients ; 13(5)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068965

RESUMO

Fat mass (FM) gain and lean mass (LM) loss are common side effects for patients with prostate cancer receiving androgen deprivation therapy (ADT). Excess FM has been associated with an increased risk of developing obesity-related comorbidities, exacerbating prostate cancer progression, and all-cause and cancer-specific mortality. LM is the predominant contributor to resting metabolic rate, with any loss impacting long-term weight management as well as physical function. Therefore, reducing FM and preserving LM may improve patient-reported outcomes, risk of disease progression, and ameliorate comorbidity development. In ADT-treated patients, exercise and nutrition programs can lead to improvements in quality of life and physical function; however, effects on body composition have been variable. The aim of this review was to provide a descriptive overview and critical appraisal of exercise and nutrition-based interventions in prostate cancer patients on ADT and their effect on FM and LM. Our findings are that FM gain and LM loss are side effects of ADT that could be reduced, prevented, or even reversed with the implementation of a combined exercise and nutrition program. However, the most effective combination of specific exercise and nutrition prescriptions are yet to be determined, and thus should be a focus for future studies.


Assuntos
Androgênios/uso terapêutico , Terapia por Exercício , Exercício Físico , Estado Nutricional , Neoplasias da Próstata/terapia , Antineoplásicos Hormonais/uso terapêutico , Composição Corporal/efeitos dos fármacos , Ingestão de Energia , Terapia de Reposição Hormonal , Humanos , Masculino , Força Muscular/efeitos dos fármacos , Músculo Esquelético , Qualidade de Vida , Testosterona/metabolismo
13.
Breast Cancer Res Treat ; 188(3): 779-788, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33948777

RESUMO

PURPOSE: To identify a structure to explain the relationship between socio-clinico factors, necessity-concerns beliefs, and perceived barriers to adherence with adjuvant endocrine therapy (AET) amongst women with breast cancer. METHODS: Participants were 244 patients with early-stage breast cancer recruited from two tertiary hospitals from May 2015 to December 2018 who completed questionnaires on medication adherence (Simplified Medication Adherence Questionnaire), necessity-concerns beliefs (Beliefs about Medicine Questionnaire), and barriers to adherence (Adherence Starts with Knowledge Questionnaire). Socio-clinico variables were collected via interview and medical records review. Structural equation modelling was applied to examine the relationships between these variables and possible mediating effects of necessity-concerns beliefs on adherence to AET. RESULTS: The median age of the study participants was 61 (range 32-80) years and the median duration on AET was 1.6 (IQR 1.2-2.6) years. Adherence was positively associated with age (ß = 0.145, 95% CI: 0.011 to 0.279, p = 0.034) and negatively associated with barriers (ß = - 0.381, 95% CI: - 0.511 to - 0.251, p < 0.001). There was no effect of Necessity (ß = 0.006, 95% CI: - 0.145 to 0.158, p = 0.933) or Concerns (ß = 0.041, 95% CI: - 0.117 to 0.199, p = 0.614) on adherence. Necessity-concerns beliefs were also not significant mediators in the relationship between socio-clinico factors and medication adherence. CONCLUSIONS: Older age and lower barriers to adherence were associated with higher adherence scores. Necessity-concerns beliefs did not have a significant effect on adherence as majority of the patients identified forgetfulness as a reason for non-adherence.


Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Terapia Combinada , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Análise de Classes Latentes , Adesão à Medicação , Pessoa de Meia-Idade , Inquéritos e Questionários
14.
Medicine (Baltimore) ; 100(18): e25835, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950995

RESUMO

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.


Assuntos
Antineoplásicos Hormonais/farmacologia , Produtos Biológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Vesículas Extracelulares/metabolismo , Microbioma Gastrointestinal , Antineoplásicos Hormonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Humanos , Klebsiella pneumoniae/citologia , Klebsiella pneumoniae/metabolismo , Células MCF-7 , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Urina/citologia
15.
Adv Exp Med Biol ; 1187: 391-401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33983590

RESUMO

Hormone therapy is a major therapy for hormone receptor-positive breast cancer that improves survival. However, despite these hormone treatments, there are de novo or acquired resistance of breast cancer. Many studies revealed these resistance mechanisms, which are related to hormonal receptors including low expression or mutation of estrogen receptor alpha(ERα), co-factors and progesterone receptor, and with activation of growth signaling pathways such as PIK3A/Akt/mTOR pathway or cell cycle pathway. To overcome endocrine resistance based on these mechanisms, there have been many efforts in clinical studies of new agents which are representative of steroidal selective estrogen receptor down-regulator, cyclin-dependent kinase (CDK) 4/6 inhibitors, inhibitors of the PI3K/AKT/mTOR Pathway and histone deacetylase (HDAC) Inhibitors. Our studies at LBCB focused the endocrine resistance in young age and showed that age under 35 years is poor prognostic factor on not only single-center data but also Korean Breast Cancer Registry Data and that women with hormone receptor-positive breast cancer who were younger than 35 years of age had less response to anti-hormonal therapy. Also, a study for gene expression in hormone receptor-positive breast cancer at a very young age (<35) revealed that expression of cell cycle-related genes increased higher than that of premenopausal women in their forties. There have been a lot of studies and clinical trials to investigate the mechanisms of resistance to endocrine treatment and to overcome them with new drugs. However, many still do not know the precise mechanism of recurrence of breast cancer after endocrine treatment. In particular, the identification of the mechanism of endocrine resistance in young women, and the combination of drugs and clinical trials to overcome this require much effort.


Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Adulto , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Recidiva Local de Neoplasia , Fosfatidilinositol 3-Quinases , Receptores de Estrogênio/genética
16.
Curr Treat Options Oncol ; 22(6): 47, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33866442

RESUMO

OPINION STATEMENT: Prostate cancer is the second leading cause of cancer death in men, and cardiovascular disease is the number one cause of death in patients with prostate cancer. Androgen deprivation therapy, the cornerstone of prostate cancer treatment, has been associated with adverse cardiovascular events. Emerging data supports decreased cardiovascular risk of gonadotropin releasing hormone (GnRH) antagonists compared to agonists. Ongoing clinical trials are assessing the relative safety of different modalities of androgen deprivation therapy. Racial disparities in cardiovascular outcomes in prostate cancer patients are starting to be explored. An intriguing inquiry connects androgen deprivation therapy with reduced risk of COVID-19 infection susceptibility and severity. Recognition of the cardiotoxicity of androgen deprivation therapy and aggressive risk factor modification are crucial for optimal patient care.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Androstenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , COVID-19/epidemiologia , COVID-19/patologia , Cardiotoxicidade , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/etnologia , Suscetibilidade a Doenças , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Disparidades nos Níveis de Saúde , Humanos , Masculino , Neoplasias da Próstata/etnologia , SARS-CoV-2
17.
Cancer ; 127(14): 2545-2552, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33793979

RESUMO

BACKGROUND: Early discontinuation is a substantial barrier to the delivery of endocrine therapies (ETs) and may influence recurrence and survival. The authors investigated the association between early discontinuation of ET and social determinants of health, including insurance coverage and the neighborhood deprivation index (NDI), which was measured on the basis of patients' zip codes, in breast cancer. METHODS: In this retrospective analysis of a prospective randomized clinical trial (Trial Assigning Individualized Options for Treatment), women with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who started ET within a year of study entry were included. Early discontinuation was calculated as stopping ET within 4 years of its start for reasons other than distant recurrence or death via Kaplan-Meier estimates. A Cox proportional hazards joint model was used to analyze the association between early discontinuation of ET and factors such as the study-entry insurance and NDI, with adjustments made for other variables. RESULTS: Of the included 9475 women (mean age, 55.6 years; White race, 84%), 58.0% had private insurance, whereas 11.7% had Medicare, 5.8% had Medicaid, 3.8% were self-pay, and 19.1% were treated at international sites. The early discontinuation rate was 12.3%. Compared with those with private insurance, patients with Medicaid (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.23-1.92) and self-pay patients (HR, 1.65; 95% CI, 1.25-2.17) had higher early discontinuation. Participants with a first-quartile NDI (highest deprivation) had a higher probability of discontinuation than those with a fourth-quartile NDI (lowest deprivation; HR, 1.34; 95% CI, 1.11-1.62). CONCLUSIONS: Patients' insurance and zip code at study entry play roles in adherence to ET, with uninsured and underinsured patients having a high rate of treatment nonadherence. Early identification of patients at risk may improve adherence to therapy. LAY SUMMARY: In this retrospective analysis of 9475 women with breast cancer participating in a clinical trial (Trial Assigning Individualized Options for Treatment), Medicaid and self-pay patients (compared with those with private insurance) and those in the highest quartile of neighborhood deprivation scores (compared with those in the lowest quartile) had a higher probability of early discontinuation of endocrine therapy. These social determinants of health assume larger importance with the expected increase in unemployment rates and loss of insurance coverage in the aftermath of the coronavirus disease 2019 pandemic. Early identification of patients at risk and enrollment in insurance optimization programs may improve the persistence of therapy.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cobertura do Seguro/classificação , Cobertura do Seguro/estatística & dados numéricos , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Características de Residência , Estudos Retrospectivos , Estados Unidos
18.
Am J Case Rep ; 22: e930733, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33907174

RESUMO

BACKGROUND Intravenous (IV) dexamethasone is widely used in critical illness, chemotherapy, or severe COVID-19. Although glucocorticoid-induced hyperglycemia (GCIH) is well-known, there is no report describing the glycemic profile following a single dose of IV dexamethasone as captured on continuous glucose monitoring (CGM) in a patient with diabetes treated with insulin. CASE REPORT A 70-year-old woman with diabetes and pancreatic adenocarcinoma was treated with chemotherapy containing dexamethasone every other week. CGM data of 23 cycles revealed a reproducible triphasic glycemic pattern consisting of a constant hyperglycemia period, followed by a transient improvement, and ending with another hyperglycemic plateau. Given this recurrent pattern, basal insulin and correction insulin were adjusted with subsequent GCIH attenuation. CONCLUSIONS This is the first report of CGM glycemic profile following recurring doses of IV dexamethasone in a patient with diabetes treated with basal-bolus insulin. The understanding of triphasic glycemic pattern allows optimal glycemic management.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Automonitorização da Glicemia/efeitos adversos , Dexametasona/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Insulina/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Administração Intravenosa , Idoso , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Glicemia , COVID-19/tratamento farmacológico , Dexametasona/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/patologia , SARS-CoV-2
19.
Molecules ; 26(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921501

RESUMO

Prostate cancer is a very common disease, which is, unfortunately, often the cause of many male deaths. This is underlined by the fact that the early stages of prostate cancer are often asymptomatic. Therefore, the disease is usually detected and diagnosed at late advanced or even metastasized stages, which are already difficult to treat. Hence, it is important to pursue research and development not only in terms of novel diagnostic methods but also of therapeutic ones, as well as to increase the effectiveness of the treatment by combinational medicinal approach. Therefore, in this review article, we focus on recent approaches and novel potential tools for the treatment of advanced prostate cancer; these include not only androgen deprivation therapy, antiandrogen therapy, photodynamic therapy, photothermal therapy, immunotherapy, multimodal therapy, but also poly(ADP-ribose) polymerase, Akt and cyclin-dependent kinase inhibitors.


Assuntos
Neoplasias da Próstata/terapia , Animais , Antineoplásicos Hormonais/química , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunoterapia , Masculino , Fototerapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia
20.
Int J Mol Sci ; 22(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923802

RESUMO

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


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Coagulação Sanguínea , Neoplasias da Mama/tratamento farmacológico , Transição Epitelial-Mesenquimal , Inibidores da Agregação Plaquetária/efeitos adversos , Trombofilia/prevenção & controle , Adulto , Anastrozol/administração & dosagem , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Neoplasias da Mama/complicações , Células Cultivadas , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Iminas/administração & dosagem , Iminas/efeitos adversos , Iminas/uso terapêutico , Células MCF-7 , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Trombina/metabolismo , Trombofilia/tratamento farmacológico , Trombofilia/etiologia
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