RESUMO
PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model. RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality. CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
Assuntos
Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Idoso , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: Worldwide changes in the incidence, histological type, and prognosis of thyroid cancer (TC) have been observed. Regional differences in the spectrum of TC may be related to genetic factors, ionizing radiation, lifestyle, and nutritional iodine, as well as to the availability of medical services. METHODS: Analysis of records of 5864 TC patients (diagnosed between 1982 and 2001), retrieved from the Israel National Cancer Registry. RESULTS: The age-standardized incidence rate (ASR per 100,000 persons) of TC among Jewish women in 2001 was 12.45 (higher than generally reported in the world) and 3.68 among Jewish men. There was a significant increase in the ASR for TC between 1982 and 2001 in the Jewish population (by 101% among women and by 25% among men, p < 0.01 for both), mainly due to papillary carcinoma. TC incidence increased in the non-Jewish population from 2.33 to 6.02 in women (p < 0.05) and from 1.13 to 2.49 in men (p > 0.05). TC incidence was similar among immigrants from Europe and America arriving in Israel before 1990 or after 1990 for both genders. An improved 5-year survival was noted in patients diagnosed between 1992 and 1996 in comparison to patients diagnosed earlier: 1982-1986 (86% versus 78%, p < 0.01). CONCLUSIONS: A marked increase in TC incidence over the last two decades (mainly due to papillary carcinoma) has been noted in different Israeli subpopulations, being the highest in Jewish women. The increase trends were similar regardless of gender or ethnicity. The reasons for this rise in TC incidence and improvement in the survival are probably multifactorial and may relate partly to increased diagnostic vigilance and changes in clinical practice.