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1.
Cancer Prev Res (Phila) ; 9(2): 142-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26667449

RESUMEN

Aromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once daily (QD, standard dose arm), 2.5 mg every Monday, Wednesday, and Friday (Q-MWF), 1.0 mg Q-MWF, or 0.25 mg Q-MWF for 24 weeks. Primary endpoint was suppression in serum estradiol levels at the end of letrozole intervention. Secondary endpoints included changes in serum estrone, testosterone, C-telopeptide (marker of bone resorption), lipid profile, and quality-of-life measures (QoL) following treatment. Significant estrogen suppression was observed in all dose arms with an average of 75% to 78% and 86% to 93% reduction in serum estradiol and estrone levels, respectively. There were no differences among dose arms with respect to changes in C-telopeptide levels, lipid profile, adverse events (AE), or QoL measures. We conclude that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile compared with standard dose. Further studies are needed to determine the feasibility of selecting an effective AI dosing schedule with better tolerability.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma in Situ/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Nitrilos/uso terapéutico , Triazoles/uso terapéutico , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Letrozol , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Posmenopausia , Pronóstico
2.
Blood Coagul Fibrinolysis ; 25(3): 248-53, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24674880

RESUMEN

Although cancer-mediated changes in hemostatic proteins unquestionably promote hypercoagulation, the effects of neoplasia on fibrinolysis in the circulation are less well defined. The goals of the present investigation were to determine if plasma obtained from patients with breast, lung, pancreas and colon cancer was less or more susceptible to lysis by tissue-type plasminogen activator (tPA) compared to plasma obtained from normal individuals. Archived plasma obtained from patients with breast (n = 18), colon/pancreas (n = 27) or lung (n = 19) was compared to normal individual plasma (n = 30) using a thrombelastographic assay that assessed fibrinolytic vulnerability to exogenously added tPA. Plasma samples were activated with tissue factor/celite, had tPA added, and had data collected until clot lysis occurred. Additional, similar samples had potato carboxypeptidase inhibitor added to assess the role played by thrombin-activatable fibrinolysis inhibitor in cancer-modulated fibrinolysis. Rather than inflicting a hypofibrinolytic state, the three groups of cancers demonstrated increased vulnerability to tPA (e.g. decreased time to lysis, increased speed of lysis, decreased clot lysis time). However, hypercoagulation manifested as increased speed of clot formation and strength compensated for enhanced fibrinolytic vulnerability, resulting in a clot residence time that was not different from normal individual thrombi. In sum, enhanced hypercoagulability associated with cancer was in part diminished by enhanced fibrinolytic vulnerability to tPA.


Asunto(s)
Fibrinólisis/efectos de los fármacos , Neoplasias/sangre , Activador de Tejido Plasminógeno/farmacología , Adulto , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Neoplasias del Colon/sangre , Neoplasias del Colon/patología , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neoplasias/patología , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/patología , Adulto Joven
3.
Blood Coagul Fibrinolysis ; 24(8): 809-13, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24145726

RESUMEN

Breast cancer is an important health threat to women worldwide, and is associated with a 9-14% incidence of thrombophilia. Of interest, patients with breast cancer have been noted to have an increase in endogenous carbon monoxide production via upregulation of heme oxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo, we sought to determine whether patients with breast cancer had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. Breast cancer patients who were not smokers scheduled to undergo partial or complete mastectomy (n = 18) had 15 ml of whole blood collected via an indwelling intravenous catheter and anticoagulated with sodium citrate. Whole blood was centrifuged and citrated plasma assessed with a thromboelastometric method to measure coagulation kinetics and the formation of carboxyhemefibrinogen. Breast cancer patients were determined to have an abnormally increased carboxyhemoglobin concentration of 2.5 ±â€Š1.3%, indicative of heme oxygenase-1 upregulation. Breast cancer patient plasma on average clotted 73% more quickly and had 32% stronger thrombus strength than normal individual (n = 30) plasma. Further, 44% of breast cancer patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal individuals, and 75% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by heme oxygenase-1-derived carbon monoxide in the pathogenesis of breast cancer-related thrombophilia is warranted.


Asunto(s)
Neoplasias de la Mama/enzimología , Carboxihemoglobina/metabolismo , Carcinoma Ductal de Mama/enzimología , Carcinoma Lobular/enzimología , Fibrinógeno/metabolismo , Hemo-Oxigenasa 1/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Pruebas de Coagulación Sanguínea , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/terapia , Monóxido de Carbono/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Carcinoma Lobular/terapia , Femenino , Hemo-Oxigenasa 1/genética , Humanos , Mastectomía Radical , Mastectomía Segmentaria , Persona de Mediana Edad , Regulación hacia Arriba
4.
J Surg Oncol ; 108(3): 163-8, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23861196

RESUMEN

BACKGROUND AND OBJECTIVES: This study was performed to investigate recent trends and factors associated with immediate breast reconstruction (IBR) using a large population-based registry. We hypothesized that rates of IBR have increased since passage of the Women's Health and Cancer Rights Act of 1998. METHODS: The SEER (surveillance, epidemiology and end results) database was used to evaluate Stage I-III breast cancer (BC) patients who underwent total mastectomy from 1998 to 2008. Univariate and multivariate analyses were performed to study predictors of IBR. RESULTS: Of 112,348 patients with BC treated by mastectomy 18,001 (16%) had IBR. Rates of IBR increased significantly from 1998 to 2008 (P < 0.0001). Use of IBR significantly decreased as patient age increased (P < 0.0001), as stage increased (P < 0.0001), and as the number of positive lymph nodes increased (P < 0.0001). Estrogen receptor+/progesterone receptor+ (ER+/PR+) patients had significantly higher IBR rates than ER-/PR-patients (P < 0.0001). IBR was used in 3,615 of 25,823 (14.0%) of patients having post-mastectomy radiation (XRT) and in 14,188 of 86,513 (16.4%) of those not having XRT (P < 0.0001). CONCLUSIONS: The utilization of IBR has increased significantly over the last decade. IBR was found to be significantly associated with age, race, geographical region, stage, ER, grade, LN status, and XRT (P < 0.0001).


Asunto(s)
Neoplasias de la Mama/cirugía , Mamoplastia/tendencias , Mastectomía , Programa de VERF , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias
5.
Cancer Prev Res (Phila) ; 6(6): 577-84, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23554130

RESUMEN

Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 µg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-ß1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.


Asunto(s)
Anticarcinógenos/farmacología , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Mama/patología , Ciclohexenos/farmacología , Terpenos/farmacología , Anticarcinógenos/farmacocinética , Mama/efectos de los fármacos , Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Caspasa 3/metabolismo , Citrus/química , Ciclina D1/metabolismo , Ciclohexenos/análisis , Ciclohexenos/farmacocinética , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Interleucina-6/metabolismo , Limoneno , Persona de Mediana Edad , Monoterpenos/análisis , Estadificación de Neoplasias , Proyectos Piloto , Pronóstico , Terpenos/farmacocinética , Distribución Tisular , Factor de Crecimiento Transformador beta1/metabolismo
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