RESUMO
PURPOSE: Improved therapies and imaging modalities are needed for the treatment of breast cancer brain metastases (BCBM). ANG1005 is a drug conjugate consisting of paclitaxel covalently linked to Angiopep-2, designed to cross the blood-brain barrier. We conducted a biomarker substudy to evaluate 18F-FLT-PET for response assessment. METHODS: Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m2 IV every 21 days. Before and after cycle 1, patients underwent PET imaging with 18F-FLT, a thymidine analog, retention of which reflects cellular proliferation, for comparison with gadolinium-contrast magnetic resonance imaging (Gd-MRI) in brain metastases detection and response assessment. A 20 % change in uptake after one cycle of ANG1005 was deemed significant. RESULTS: Thirty-two target and twenty non-target metastatic brain lesions were analyzed. The median tumor reduction by MRI after cycle 1 was -17.5 % (n = 10 patients, lower, upper quartiles: -25.5, -4.8 %) in target lesion size compared with baseline. Fifteen of twenty-nine target lesions (52 %) and 12/20 nontarget lesions (60 %) showed a ≥20 % decrease post-therapy in FLT-PET SUV change (odds ratio 0.71, 95 % CI: 0.19, 2.61). The median percentage change in SUVmax was -20.9 % (n = 29 lesions; lower, upper quartiles: -42.4, 2.0 %), and the median percentage change in SUV80 was also -20.9 % (n = 29; lower, upper quartiles: -49.0, 0.0 %). Two patients had confirmed partial responses by PET and MRI lasting 6 and 18 cycles, respectively. Seven patients had stable disease, receiving a median of six cycles. CONCLUSIONS: ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and 18F-FLT-PET imaging.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Paclitaxel/análogos & derivados , Peptídeos/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores , Biomarcadores Tumorais , Neoplasias Encefálicas/diagnóstico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Terapia Combinada , Feminino , Fluordesoxiglucose F18 , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Tomografia por Emissão de Pósitrons , Resultado do TratamentoRESUMO
PURPOSE/OBJECTIVES: To review literature that explores the relationship between stress and the development of breast cancer and investigates the immune system as a possible mediator. Personality traits, response to stress, and stressful life events are considered. DATA SOURCES: Published articles, book chapters, books, and workbooks from nursing and medical literature. DATA SYNTHESIS: Studies show that a relationship exists between stress and the development of breast cancer. Most of the literature describes this relationship according to the patient's personality traits, her response to stress, or the occurrence of stressful life events. The immune system may mediate the physiologic influence of stress on breast cancer. CONCLUSIONS: Although the difficulty of measuring stress makes it difficult to demonstrate a tangible relationship between stress and breast cancer, studies reveal that stress is related to breast cancer in various ways. Dealing positively with stress may improve the quality of life of patients with breast cancer. IMPLICATIONS FOR NURSING PRACTICE: Nurses must understand the ubiquitous nature of stress and its relationship to breast cancer. Although they may not be able to prevent stress, patients can learn techniques (e.g., stress management, social support, communication, laughing and crying) to deal with it positively.