RESUMO
PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83). CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.
Assuntos
Carcinoma Intraductal não Infiltrante/radioterapia , Doenças Cardiovasculares/mortalidade , Sobreviventes , Neoplasias Unilaterais da Mama/radioterapia , Fatores Etários , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Intraductal não Infiltrante/etiologia , Carcinoma Intraductal não Infiltrante/cirurgia , Doenças Cardiovasculares/etiologia , Causas de Morte , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Estudos de Coortes , Terapia Combinada/métodos , Intervalos de Confiança , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Coração/efeitos da radiação , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/mortalidade , Humanos , Irradiação Linfática , Mastectomia , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/mortalidade , Países Baixos , Radioterapia/efeitos adversos , Radioterapia/métodos , Sistema de Registros , Medição de Risco , Fatores de Tempo , Neoplasias Unilaterais da Mama/patologia , Neoplasias Unilaterais da Mama/cirurgiaRESUMO
Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases serum levels of total IGF-I in premenopausal women with 1) a history of breast cancer (n=24) or 2) a high familial breast cancer risk (n=36). Also, IGF binding protein (IGFBP) increasing effects were evaluated. Lycopene supplementation did not significantly alter serum total IGF-I and other IGF system components in the 2 study populations combined. However, statistically significant discordant results were observed between the 2 study populations (i.e., P<0.05 for total IGF-I, free IGF-I, and IGFBP-3). Total IGF-I and IGFBP-3 were increased in the breast cancer survivor population [total IGF-I=7.0%, 95% confidence interval (CI)= -0.2 to 14.3%; IGFBP-3=3.3%, 95% CI=0.7-6.0%), and free IGF-I was decreased in the family history population (-7.6%, 95% CI= -14.6 to -0.6%). This randomized controlled trial shows that 2 mo of lycopene supplementation has no effect on serum total IGF-I in the overall study population. However, lycopene effects were discordant between the 2 study populations showing beneficial effects in high-risk healthy women but not in breast cancer survivors.