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1.
Breast Cancer Res Treat ; 159(3): 481-8, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27568021

RESUMEN

Breast cancer in African-American females (AAF) has a less favorable outcome than that in Caucasians. More information is needed regarding its biology. We evaluated gene expression in tumors from AAF presenting with early stage or locally advanced breast cancer using MammaPrint(®), BluePrint (®) (molecular subtype) and TargetPrint (®) [estrogen receptor (ER), progesterone receptor, and Human Epidermal Growth Factor Receptor 2 (HER2) mRNA levels]. Genomic information was correlated with clinical and pathologic characteristics and Oncotype DX(®) Recurrence Score(®) (RS). One hundred Patients were enrolled, 1 not evaluable by BluePrint. The median age was 60 years (range 22-98), and eighty-four (84 %) patients had stage I or II disease. High Risk MammaPrint was present in 66 % of patients and in 52 % of patients with stage I disease. High Risk MammaPrint was associated with young age (p = 0.02), high grade (p < 0.0001), HER2 expression (p = 0.016), and triple-negative phenotype (p < 0.001). Sixty-four tumors (65 %) were Luminal type (47 % of these were classified as High Risk), 26 (26 %) were Basal type, and 9 (9 %) HER2 type. Twenty-two cancers were triple negative (TN) by IHC and 19 (90 %) Basal type. Among the 15 tumors HER2 positive by IHC/FISH, 8 (53 %) were HER2 type by BluePrint. Eleven tumors with ER expression of 1-9 % were ER negative by TargetPrint and none of these was Luminal type. None of the seven tumors HER2 positive by IHC/FISH but negative by TargetPrint was HER type. RS results were available in 29 patients: two had High Risk both by RS and MammaPrint; eight had intermediate RS, with four High Risk by MammaPrint; 19 had a low RS, with eight High Risk by MammaPrint. AAF with stage I to III breast cancer often present with High Risk disease. Molecular heterogeneity is present within TN, HER2-positive, and ER-positive breast cancer. RS and MammaPrint offer different prognostic information.


Asunto(s)
Negro o Afroamericano/genética , Neoplasias de la Mama/genética , Perfilación de la Expresión Génica/instrumentación , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Heterogeneidad Genética , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estados Unidos/etnología , Adulto Joven
2.
Breast Cancer Res Treat ; 155(2): 285-93, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26749359

RESUMEN

Animal data suggest that defects in BRCA1/2 genes significantly increase the risk of heart failure and mortality in mice exposed to doxorubicine. Women with BRCA1/2 mutations who develop breast cancer (BC) may receive anthracyclines but their risk of cardiac dysfunction has not been investigated. Our study tested the hypothesis that women with history of BRCA1/2 mutation-associated BC treated with anthracyclines have impaired parameters of cardiac function compared to similarly treated women with history of sporadic BC. Women with history of BC and anthracycline treatment underwent an echocardiographic exam for assessment of primary outcomes, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). The sample size of 81 provided 79 % power with two-sided two-sample t test and alpha of 0.05 to detect a clinically meaningful difference in cardiac function of absolute 5 % points difference for LVEF and 2 % points difference for GLS. Of 81 normotensive participants, 39 were BRCA1/2 mutation carriers and 42 in the sporadic group. Mean age was 50 ± 9 years in both groups (P = 0.99) but BRCA1/2 mutation carriers had longer anthracycline treatment-to-enrollment time (7.5 ± 5.3 vs. 4.2 ± 3.3 years, P = 0.001). There were no significant differences in LVEF (P = 0.227) or GLS (P = 0.53) between the groups. LVEF was normal in 91 % of women and subclinical cardiac dysfunction defined as absolute GLS value <18.9 % was seen in 4 (10 %) BRCA1/2 mutation carriers and 7 (17 %) sporadic participants. In this first prospective examination of cardiac function in BRCA1/2 mutation carriers, we found no significant differences in sensitive echocardiographic parameters of cardiac function between BRCA1/2 mutation carriers and women with history of sporadic BC who received anthracycline treatment. In contrast to laboratory animal data, our findings indicate lack of elevated cardiac risk with the use of standard-doses of adjuvant anthracyclines in treatment of BRCA1/2 mutation carriers with early stage BC.


Asunto(s)
Antraciclinas/efectos adversos , Antraciclinas/uso terapéutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Función Ventricular Izquierda/efectos de los fármacos , Adulto , Neoplasias de la Mama/genética , Doxorrubicina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Mutación/genética , Estudios Prospectivos , Volumen Sistólico/efectos de los fármacos
3.
Eur J Endocrinol ; 174(3): 373-80, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26671977

RESUMEN

OBJECTIVE: Our objective was to evaluate the efficacy and safety of sunitinib following at least one course of radioactive iodine treatment in patients with advanced differentiated thyroid cancer (DTC). The study endpoints included best response rate (including best objective response rate) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, measurement of serum thyroglobulin (Tg), and toxicity evaluation. DESIGN AND METHODS: This was a single center, nonrandomized, open-label, phase 2 clinical trial. In total, 23 patients were enrolled and were treated with a starting daily, oral dose of 37.5  mg sunitinib. Patients were evaluated with imaging, laboratory tests, and physical examination periodically per protocol. RESULTS: The mean best response was a decrease of 17.2% (S.D. 22.8) in tumor sum from baseline. Six (26%) patients achieved a partial response (PR), and 13 (57%) had stable disease (SD) for a clinical benefit rate (PR+SD) of 83%. The overall median PFS was 241 days (interquartile limits, 114-518). No statistically significant difference was observed between the medians of the baseline and post-treatment Tg values (P=0.24). The most common adverse events included grades 1 and 2 decreases in blood cell counts (especially leukocytes), diarrhea, fatigue, hand-foot skin reaction, nausea, musculoskeletal pain, and hypertension. CONCLUSIONS: These data demonstrate that sunitinib exhibits significant anti-tumor activity in patients with advanced DTC. Since sunitinib was relatively well-tolerated, there is the potential for clinical benefit in these patients, and further investigation of this agent is warranted.


Asunto(s)
Adenocarcinoma Folicular/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Indoles/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Pirroles/uso terapéutico , Radioterapia , Neoplasias de la Tiroides/tratamiento farmacológico , Adenocarcinoma Folicular/patología , Adenoma Oxifílico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Carcinoma/patología , Carcinoma Papilar , Quimioterapia Adyuvante , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Fatiga/inducido químicamente , Femenino , Síndrome Mano-Pie/etiología , Humanos , Leucopenia/inducido químicamente , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Sunitinib , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología
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