Survival of patients with metastatic breast carcinoma

Abstract

BACKGROUNDWomen with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. Therefore, the authors tested the hypothesis that the characteristics of primary breast tumors are important determinants of prognosis and survival in patients with metastatic breast carcinoma.METHODSThe prognostic significance of the biology of the primary tumor for outcome in patients with metastatic breast disease was assessed in 346 patients with lymph node positive breast carcinoma who developed distant, recurrent disease. Traditional prognostic indicators (age, tumor size, number of involved lymph nodes, sites of recurrence, disease free interval [DFI], adjuvant treatments, estrogen receptor [ER] expression, progesterone receptor [PgR] expression, S‐phase fraction [SPF], and DNA ploidy), together with three newer biologic markers (c‐erbB‐2, p53, and bcl‐2) were assessed. Sites of recurrence were defined as nonvisceral (bone and locoregional lymph nodes) or visceral (lung, liver, brain, and other organs).RESULTSThe median duration of survival was 17.8 months (95% confidence interval, 15.2–21.5 months). Univariate analysis showed that age > 50 years, visceral disease, and shorter DFI were associated significantly with poor outcome (P < 0.05). In addition, the molecular phenotype of the primary breast tumor was significant, with primary tumors that showed ER negativity and PgR negativity, high SPF, aneuploidy, accumulation of p53 protein, and lower bcl‐2 expression, together with c‐erbB‐2 overexpression, all associated with a poorer clinical outcome (P < 0.05). In a multivariate analysis, older age, visceral disease, shorter DFI, PgR negativity, high SPF, and lower bcl‐2 expression were significant predictors of worse survival (P < 0.05).CONCLUSIONSIn addition to traditional risk factors, bcl‐2 negativity was associated significantly with a worse clinical outcome. Biologic features of primary tumors were correlated independently with outcome after first recurrence in patients with metastatic breast carcinoma and may be used as indicators of prognosis in the metastatic setting. Cancer 2003;97:545–53. © 2003 American Cancer Society.DOI 10.1002/cncr.11083

Metastatic breast cancer: clinicopathological features and survival according to the site of metastasis

“…O acometimento hepático ocorre em um terço a metade das pacientes com câncer de mama metastático, agressividade e velocidade de crescimento tumoral. 17,18 A relação entre o tempo livre de doença e o sítio metastático ainda é contraditória, observando-se em algumas populações maior tempo de sobrevida livre de metástase nas pacientes com metástase óssea isolada 12 e, em outras, tempos de sobrevida equivalentes nos dois sítios. 20 Em nosso estudo, não se observou diferença estatisticamente significativa em relação ao tempo livre de doença metastática segundo o sítio da metástase, observando-se 29,1 meses na metástase óssea isolada e 24,3 meses na extraóssea (semelhante aos valores descritos na literatura, os quais variam entre 25 e 40 meses).…”

“…Já o tempo de sobrevida após o acometimento extraósseo (12,1 meses) também foi semelhante aos valores observados em estudos internacionais com grandes populações, os quais variam entre 11 e 16 meses. 11,12,17,20 Em linhas gerais, apesar de diferenças metodológicas, pode-se considerar que o tempo de sobrevida por câncer de mama metastático em nosso meio foi semelhante à literatura internacional. 20,45 Embora as pacientes diagnosticadas em estágio IV do câncer de mama apresentem, de forma geral, pior prognóstico, a sobrevida global em cinco anos das pacientes que apresentaram metástase extraóssea no curso da doença foi equivalente à sobrevida global em cinco das pacientes com metástase óssea no momento do diagnóstico (24,8; IC95%: 15,2-35,7 e 26,7%; IC95%: 4,1-57,9, respectivamente).…”

“…19 O sítio de metástase é um fator prognóstico independente para a sobrevida das mulheres com neoplasia maligna da mama. [16][17][18][19][20][21][22] No Brasil, embora alguns autores tenham avaliado a sobrevida do cân-cer de mama segundo a presença de metástase à distância, 23,24 ainda pouco se abordou essa questão no que se refere aos sítios metastáticos acometidos. Vale lembrar que, além de investigarem o impacto de características inerentes ao tumor, os dados de sobrevida são o parâmetro mais utilizado para avaliar resultados na área oncológica, permitindo identificar avanços diagnósticos e terapêuti-cos, bem como analisar a eficiência global do controle do câncer pelo sistema de saúde.…”

Cox Proportional Hazard Survival Analysis to Inpatient Breast Cancer Cases

“…The major prognostic factors of breast cancer are associated with several possible approaches to diagnosis, including clinic stages [8], and histopathological grade [9] [10]. Survival rate depends also on the type of diagnosis based on the existence of metastasis [11][12][13]; radiologic figure of mammography [14]; and genetic expression [15]. In addition to the clinical stage stage of breast cancer or the type of diagnosis, there are several other prognostic factors associated with survival rate, namely: age [16], race [15] , occupation [17], comorbidity: diabetes [18]; anemia [7] [19], family history [7], tumor size [20] [21], location of lymph node metastasis [11] [21].…”

Identification of an ataxia telangiectasia-mutated protein mediated surveillance system to regulate Bcl-2 overexpression

“…Additionally, the observations that reduced Bcl-2 expression correlates with an unfavorable prognosis for breast cancer patients (Chang et al, 2003) are also not well understood. To investigate Bcl-2-associated tumor suppression, we ectopically expressed Bcl-2 in MCF7 breast cancer cells.…”