Circulating tumor cells (CTCs) and cytokeratin 19 (CK19) mRNA as prognostic factors in heavily pretreated patients with metastatic breast cancer.

INTRODUCTION: Circulating tumor cell (CTC) count and cytokeratin 19 (CK19) mRNA expression have a prognostic value for patients with metastatic breast cancer (MBC), but their clinical utility remains controversial. We studied CTC count and CK19 mRNA expression in the peripheral blood samples from heavily pretreated patients with MBC and their correlations with prognosis and response to the subsequent line of therapy. METHODS: This prospective observational study included 67 consecutive patients with MBC who were on progression to systemic therapy, and criteria for a new line of systemic treatment were proposed outside a clinical trial. CTC counts and CK19 mRNA expression were measured by the CellSearch® and RT-PCR methods, respectively, before and after the first cycle of treatment. Progression-free survival (PFS) was defined as the time elapsed between the initiation of the treatment and either the date of clinical or radiological tumor progression or death from any cause or the last follow-up. Cox proportional hazards regression model was used to assess the univariate prognostic value of CTC and CK19 mRNA expression on PFS and Kaplan-Meier estimates. A multivariate Cox model was also used to additionally account for phenotype and visceral disease. RESULTS: The mean age was 60 (range 35-86) years, and the average number of previous treatments was 3 (range 1-10); 42 patients (62.6%) were ER+ and 38 patients (56.7%) had visceral disease. The median PFS rate was 8 months (95% CI: 3.7-8.2). Univariate analyses showed a significant effect of the initial value of CK19 mRNA expression (HR = 2.00; 95% CI: 1.05-3.8; p = 0.03) and for the second value of CTC (HR = 2.18; 95% CI: 1.22-3.9; p = 0.009) but did not reach statistical significance for the initial value of CTC and the second value of CK19 mRNA expression. The estimated PFS rates at 6 and 12 months were 75% and 31% for patients with a low initial value of CK19 mRNA expression and 36% and 10% for those with a high initial value of CK19 mRNA expression, respectively (p: 0.022). Further, the estimated PFS rates at 6 and 12 months were 86% and 65% for patients with a low second value of CTC and 76% and 47% for those with a high second value of CTC, respectively (p: 0.004). In the multivariate analysis adjusted for phenotype, visceral disease, and the last treatment performed, only the effect of the second value of CTC remained significant (HR = 2.7, p = 0.004). CONCLUSIONS: CK19 mRNA expression and CTC count appeared clinically meaningful in pretreated patients with MBC, even when adjusted for phenotype and visceral disease involvement. These results support the use of CK19 and CTC as relevant biomarkers for predicting clinical response in MBC.

Influencia de la elevación del índice tobillo/brazo en el riesgo cardiovascular y supervivencia en varones adultos sin enfermedad arterial periférica / Influence of an increased ankle/brachial index on cardiovascular risk and survival in adult men with no peripheral arterial disease

Objetivo: La significación clínica del índice tobillo/brazo (IT/B) elevado y su asociación a enfermedad cardiovascular es controvertida. Nuestro objetivo fue evaluar la asociación entre la elevación basal del IT/B con el riesgo de mortalidad cardiovascular (MCV), mortalidad total (MT) y aumento de evento coronario mayor (ECM) tras 5 años de seguimiento en una población mediterránea. Sujetos y métodos: Estudio poblacional prospectivo de 614 varones entre 55 y 74 años sin enfermedad arterial periférica. Medición basal de factores de riesgo cardiovascular (FRCV) e IT/B categorizados. Las categorías de IT/B fueron: 0,9-1,24(A), 1,25-1,34(B), ≥1,35(C). Los ECM, la MCV y MT fueron evaluadas durante el seguimiento. Resultados: La distribución de los sujetos según su mayor IT/B fue: A=441(71,8%), B=113 (18,4%) y C=60 (9,7%). En referencia al grupo A (IT/B normal), los sujetos del grupo B y C presentaban mayor prevalencia de hipertensión (p<0,01), tabaquismo (p<0,01) y colesterol elevado (p=0,04), siendo similares otros FRCV evaluados. Tras 5 años de seguimiento, y ajustando por posibles factores confusores, el riesgo de MCV y MT para los sujetos del grupo B en relación al grupo A fue de 1,33 (0,48-3,6, p=0,57) y 1,07 (0,55-2,08, p=0,83), respectivamente, y para los del grupo C fue de 0,53 (0,07-4,02, p=0,54) y 0,79 (0,28-2,22, p=0,66). Las diferencias de riesgo de ECM entre los grupos tampoco fue significativa (p=0,07 grupo B y p=0,97 grupo C, respecto A). Conclusiones: En nuestro estudio, la elevación del IT/B se asocia con una mayor prevalencia de algunos FRCV, sin embargo, este hallazgo hemodinámico no parece asociarse con un riesgo independiente adicional de ECM o mortalidad en nuestro medio(AU)

Objective: The clinical significance of an increased ankle/brachial index (ABI) and its association with risk factors and cardiovascular disease has been subject of controversy. Our objective was to evaluate the association between an increased baseline ABI with the risk of cardiovascular mortality (CVM), total mortality (TM) and increased major coronary events (MCE) at 5 years of follow-up in a Mediterranean population. Subjects and methods: A prospective survey was conducted on 614 men between 55 and 74 years-old with no peripheral arterial disease and representative of an urban district near Barcelona (Spain). Baseline cardiovascular risk factors and categorised ABI were recorded. ABI categories were: 0.9-1.24 (A), 1.25-1.34 (B), ≥1.35 (C). MCE, mortality and their cause were evaluated during 5-years of follow-up. Results: The distribution of subjects according to their ABI was: A=441 (71.8%), B=113 (18.4%) and C=60 (9.7%). The B and C group subjects had a higher prevalence of hypertension (P<.01), higher cholesterol plasma levels (P=.04) and smokers (P<0.01) compared to the normal ABI group (A), with the other risk factors assessed being similar. At 5-year follow-up (mean 65 months), and after adjustment for confounding factors, CVM and TM risk for B subjects were 1.33 (0.48-3.6, P=.57) and 1.07 (0.55-2.08, P=.83) respectively, compared to the normal ABI group (A). For C subjects they were 0.53 (0.07-4.02, P=.54) and 0.79 (0.28-2.22, P=.66). There were no significant differences in MCE risk between ABI groups (P=.07 for B and P=0.97 for C, related to A). Conclusions: In our study, an increased ABI is associated with a higher prevalence of some risk factors; however this haemodynamic finding does not seem to be associated with an additional independent risk of MCE or mortality in our setting(AU)

The association of peripheral arterial occlusive disease with major coronary events in a mediterranean population with low coronary heart disease incidence.

OBJECTIVES: The association of peripheral arterial occlusive disease (PAD) association with major coronary events (MCE) has been well documented, nevertheless data are lacking for populations with a low incidence of coronary heart disease (CHD). We aimed to assess the association of PAD with MCE in a Mediterranean population. DESIGN: Prospective survey of 699 55-74 year-old men representative of an urban district near Barcelona (Spain). METHODS: Baseline cardiovascular risk factors, CHD and PAD (ankle/brachial index<0.9) were recorded. MCE were evaluated during the 5-year follow-up. RESULTS: At recruitment 94 subjects (13.4%) had PAD. During follow-up (mean 69.3 months), 35 (5%) subjects suffered a MCE, of whom 12 had PAD, 9 previous symptomatic CHD and 1 subject both conditions. Higher CHD related mortality (8.6% vs 1.4%; p<0.001) and lower MCE-free survival (78.67% vs 93.26%; p<0.001) was observed for PAD subjects. On Cox regression analysis PAD (RR=3; p=0.003) and previous symptomatic CHD (RR=4.1; p<0.001) were associated independently with MCE during follow-up. CONCLUSIONS: Even in a population with a low incidence of CHD there is a strong relationship between PAD and future MCE. Screening for PAD may improve the selection of patients targeted for cardiovascular risk prevention.

Relationship of obesity distribution and peripheral arterial occlusive disease in elderly men.

OBJECTIVE: To examine the relationships between total body fatness and abdominal fat distribution with peripheral arterial disease. DESIGN: Cross-sectional. SUBJECTS: Population-based sample of 708 men aged 55-74. MEASUREMENTS: Body mass index (BMI) to estimate total body fatness and waist-to-hip ratio for abdominal fat distribution; peripheral arterial disease defined by ankle/brachial index <0.9; cardiovascular risk factors. RESULTS: Peripheral arterial disease was observed in 13.4% of subjects. BMI did not correlate with peripheral arterial disease, whereas an increased waist-to-hip ratio over 0.966 (median value) doubled the prevalence of arterial disease. After controlling for smoking, diabetes, hypertension, high-density lipoprotein cholesterol and triglycerides, increased waist-to-hip ratio was independently associated with peripheral arterial disease (odds ratio 1.68; 95% confidence interval 1.05-2.70). CONCLUSION: Abdominal fat distribution, but not total body fatness, is associated with peripheral arterial occlusive disease, independently of concurrent cardiovascular risk factors.