| objectives:μ. To explore the predictive value serum cancer antigen153(CA153)、 carcino-embryonic antigen (CEA) and cancer antigen125(CA125) for breast cancer patients with bone metastases2. To discuss the relationship between baseline characteristics (TNM stage,number of bone metastatic region,number of ectosteal metastatic region,expression of HER-2(Human Epidermal Growth Factor Receptor2), estrogen receptor(ER) and progesterone receptor(PR), menopausal status) and serum levels of CA153and CEA in patients with breast cancer.3. To investigate the relationship between the serum CA153,CEAand CA125. and onset time of bone metastasis in breast carcinoma.4.To analyze the association between baseline characteristics (TNM stage,number of bone metastatic region, number of ectosteal metastatic region,expression of HER-2.ER and PR, enopausal status) and onset time of bone metastasis. Methods:1. The samples were obtained from nanfang hospital and guangzhou panyu central hospital between June2001and June2010.140patients (139female,1male) with breast cancer confirming by pathology were included。 We studyed and analyzed the serum level of CA153,CEA and CA125detecting by ELISA(enzyme linked immunosorbent assay). The ages of patients ranges from26to89with the median age of50.70patients developed bone metastases after operation,64cases occurred within1to5years and6cases formore than5years after operation.Among them,39patients were examined for serum level of CEA^CA153before and after diagnosis of bone metastases. The control group consisted of70patients with no bone metastases for at less5years after the operation. In the140available patients,128was diagnosed of infitrating ductal carcinoma(IDC) and12was diagnosed ofbreast cancer of other types.2. Evaluation criterion for bone metastases in breast cancer:Breast cancer was diagnosed with pathological sections of surgical specimen;ECT was performed and reviewed by at least2nuclear medicine physicians, patients with multiple,sporadic,randomized distributing radioactive concentrating lesions and relevant history, symptoms or phisical signs were diagnosed as bone metastasis in breast cancer..Patients with few abnormal radioactive concentrating lesions should be confirmed by either X-ray,CT scan or biopsy.3.70patients with bone metastasis had blood draw in the next day after the diagnosis for the test of serum CA153、CEA、CA125withEIISA.Among them,39cases were examined serum CA153and CEA both before and after the diagnosis.The control group had blood draw before operation for the detection of CA153,CEA and CA125with ELISA.4. Serum CA153,CEA and CA125were examined in140cases. ROC curve was used to analyze specificity and sensibility of each tumor markers for bone metastases in breast cancer.5. Statistical analysis:SPSS13.0software was used. Changes in serum levels of CA153and CEA before and after metastasis(n=39) of breast cancer patients were analyzed with paired non-parametric test and Spearman’s rank correlation, while the correlation between baseline characteristics and CA153,CEA was analyzed with Paired t test.Serum CA153,CEA and CA124in patients with or without bone metastasis were analyzed with independent non-parametric test and Spearman’s rank correlation. Predictive specificities of serum CA153,CEA and CA125were analyzed with ROC curve. Discriminatory analysis was applied to evaluate the specifity of combined detection. All data were measured by mean+standard deviation. P<0.05was considered statistically significant.Results:1. Area under ROC curves of CA153, CEA and CA125were0.800,0.849,0.803, respectively and statistical significant.(p=0.000,p=0.000, p=0.000,respectively). Youden index of three markers were1.454,1.454and1.404,respectively.2. Area under ROC curves of conbined detection was0.853, which exceeded those of individual detection of either marker and displayed the highest sensitivity.Hence,combine detection would improve the sensitivity of diagnosis for bone metastasis in breast cancer.3. Significant differences were showed in serum levels of CA153(Z=-6.181, P=0.000),CEA (Z=-6.126,P=0.000) and CA125(Z=-7.129,P=0.000) before and after bone metastasis.None of three markers was significantly correlated with bone metastasis(r=0.037, p=0.759for CA153; r=0.167,p=0.168for CEA; r=-0.081, p=0.507for CA125.)4. In breast cancer patients with bone metastasis(n=39),serum levels of CA153before and after metastasis showed significant differences(Z=-3.821, p=0.000),which also indicated correlation with bone metastasis(r=0.429, P=0.006). Serum levels of CA153in patients with either HER(-),menses, stage III-IV or>5bone metastatic region showed significant difference before and after metastasis(t=3.41, p=0.003; t=2.55, p=0.021; t=2.71, p=0.012; t=2.39,p=0.034).Patients with HER(-),stage III-IV disease,>5bone metastatic region,<l ectosteal bone metastatic region or PR(-) showed correlation between elevated serum CA153and bone metastasis(r=0.610, p=0.002; r=0.435, p=0.033; r=0.697, p=0.008; r=0.702,p=0.004; r=0.530, p=0.020)).Serum levels of CEA were significantly different before and after metastasis(Z=-3.198, p=0.001),with also significant correlation with bone metastasis(r=0.525, p=0.001).Among them, patients with either HER-2(-), menopause,stage II disease,<5bone metastatic region,>5bone metastatic region, ER(-), ER(+), PR(-) or PR(+) displayed elevated serum CEA after metastasis, suggesting correlations with bone metastasis(r=0.749, P=0.000; r=0.999, P=0.000; r=1.000, P=0.000; r=0.752, P=0.000; r=1.000, P=0.000; r=0.998,P=0.000; r=0.660, P=0.000; r=0.998, P=0.000; r=0.440, i^0.040)5.In patients with bone metastasis, ECOG score was significantly correlated with onset time of bone metastasis(P=0.000). ER status was remarkably correlated with occurrent time of bone metastasis(P=0.015).Conclusion:1. Areas under ROC curve of either serum CA153,CEA or CA125was greater than0.5,suggesting predictive value of three biomarkers for bone metastasis in breast cancer. 2. Serum CA153,CEA and CA125were significantly increasing in patients with or without bone metastasis,indicating no association were existing between three biomarkers and bone metastasis in breast cancer.3. Serum CA153and CEA were remarkably raised after bone metastasis and correlated with the metastatic status.4. Stratified analysis according to baseline characteristics (n=39)showed that serum levels of CA153in patients with either Her-2(-),menses, stage III-IV or>5bone metastatic region is significant elevated after metastasis. Patients with Her-2(-),stage III-IV disease,>5bone metastatic region,<1ectosteal bone metastatic region or PR(-) showed correlation between elevated serum CA153and bone metastasis.5. Stratified analysis according to baseline characteristics (n=39)showed that patients with either Her-2(-), menopause,stage II disease,<5bone metastatic region,>5bone metastatic region, ER(-), ER(+), PR(-) or PR(+) displayed elevated serum CEA after metastasis, suggesting correlations with bone metastasis.6. In breast cancer patients, ECOG score and ER status were significantly correlated with onset time of bone metastasis.Patients with<2ECOG score or ER(+) were inclined to develop bone metastasis for a longer time thant control group.Certain trends were seen between bone metastasis and ages, PR status, Her-2status, number of bone metastatic regions, number of ectosteal regions, clinical stages, serum CA153, serum CEA and CA125,though no significant correlation were displayed. |
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