Androgens are involved in the development of breast cancer, although the mechanisms remain unclear. To further investigate androgens in breast cancer, we examined the relations between serum ...testosterone and age, body mass index (BMI), tumor size, histologic type, grade, axillary node involvement, estrogen receptor status, progesterone receptor status, and HER2 overexpression in a cross-sectional study of 592 postmenopausal breast cancer patients. Mean testosterone differences according to categories of patient and tumor characteristics were assayed by Fisher's or Kruskall-Wallis test as appropriate; adjusted odds ratios (OR) of having a tumor characteristic by testosterone tertiles were estimated by logistic regression. Testosterone concentrations were significantly higher in women with BMI >or=30 versus BMI <25. ORs of having a tumor >or=2 cm increased significantly with increasing testosterone tertiles, and the association was stronger in women >/=65 years. The OR of having infiltrating ductal carcinoma was significantly higher in the highest compared with the lowest testosterone tertile. ORs of having estrogen receptor- and progesterone receptor-negative versus estrogen receptor- and progesterone receptor-positive tumors decreased significantly with increasing testosterone tertiles. In women >or=70 years, those with high testosterone had a significantly greater OR of HER2-negative cancer than those with low testosterone. These results support previous findings that high-circulating testosterone is a marker of hormone-dependent breast cancer. The age-related differences in the association of testosterone with other disease and patient characteristics suggest that breast cancers in older postmenopausal women differ markedly from those in younger postmenopausal women. The relationship between testosterone and HER2 status in the oldest patients merits further investigation.
The aim of the present study was to investigate serum HER2 extracellular domain (ECD) as a putative surrogate marker of the shedding phenomenon of HER2 receptor from the tumor tissue of primary ...breast cancer (BC) patients. A pilot retrospective study was conducted on 100 matched serum and tissue samples from patients with node-positive primary BC, stage II/III. Analysis of association and concordance between serum HER2 ECD levels (measured by chemiluminescence immunoassay) and the expression in matched tumor tissue of HER2 ECD and intracellular receptor domain (ICD) (determined by immunohistochemistry) were performed. The median serum HER2 ECD level was 9.4 ng/ml and cutoff values were set at 15.2 ng/ml or 13.0 ng/ml. HER2 ICD and ECD were overexpressed in tumor tissue of 19.8% and 6.9% of patients, respectively. Statistically significant associations were found between serum HER2 ECD levels and tissue expression of both HER2 ICD and ECD (p < .001; Fisher analysis). Moreover, strong concordances were found between serum HER2 ECD levels and tissue expression of HER2 ICD or ECD (cutoff 15.2 ng/ml: 80 and 92.5%, respectively). Our findings support a role for serum HER2 ECD as a surrogate marker of tissue HER2 status in primary BC, both for HER2 ICD or ECD expression.
A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2.
Among 124 ...patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m2) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD).
Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035).
Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.
Background
Prostate-specific antigen (PSA) lacks specificity and sensitivity in
discriminating prostate cancer (PCa) from benign prostatic hyperplasia (BPH)
when the total PSA (tPSA) level is between ...4 and 10 ng/mL. It remains to be
investigated if additional tumor-associated molecules may improve the PCa
diagnostic accuracy. The aim of the present study was to investigate whether
serum levels of insulin-like growth factor 1 (IGF1), insulin-like growth
factor binding protein 3 (IGFBP3) and their combinations with PSA may
enhance the diagnosis of PCa.
Methods
Serum tPSA and free PSA (fPSA) levels were measured using an automated
chemiluminescence-based method. IGF1 and IGFBP3 levels were evaluated by
radioimmunoassays in a prospectively and consecutively enrolled subset of
149 patients with tPSA ≤10 ng/mL made up of patients with benign prostatic
hyperplasia (BPH; n = 113) and PCa (n = 36).
Results
IGF1 and IGFBP3 serum levels did not significantly differ between the PCa and
BPH groups. No important correlation was found between the IGF molecules and
PSA isoforms in both groups. Statistical analysis of the combination of
markers indicated that only the free/total PSA ratio (f/tPSA%) was
informative and independent in predicting the presence of PCa, considering
that for high values of this percentage (17%) the probability of finding PCa
decreased. Receiver operating characteristics areas under the curve (AUC)
for IGF1 and IGFBP3 were not informative (AUC ~0.5 in both cases) contrary
to the AUC for f/tPSA% (AUC = 0.689, p = 0.0002).
Conclusions
The present study showed that neither IGF1 and IGFBP3 alone nor in
combination with PSA enhance the diagnostic performance of PSA in PCa.
Background Prostate-specific antigen (PSA) lacks specificity and sensitivity indiscriminating prostate cancer (PCa) from benign prostatic hyperplasia (BPH)when the total PSA (tPSA) level is between 4 ...and 10 ng/mL. It remains to beinvestigated if additional tumor-associated molecules may improve the PCadiagnostic accuracy. The aim of the present study was to investigate whetherserum levels of insulin-like growth factor 1 (IGF1), insulin-like growthfactor binding protein 3 (IGFBP3) and their combinations with PSA mayenhance the diagnosis of PCa. Methods Serum tPSA and free PSA (fPSA) levels were measured using an automatedchemiluminescence-based method. IGF1 and IGFBP3 levels were evaluated byradioimmunoassays in a prospectively and consecutively enrolled subset of149 patients with tPSA ≤10 ng/mL made up of patients with benign prostatichyperplasia (BPH; n = 113) and PCa (n = 36). Results IGF1 and IGFBP3 serum levels did not significantly differ between the PCa andBPH groups. No important correlation was found between the IGF molecules andPSA isoforms in both groups. Statistical analysis of the combination ofmarkers indicated that only the free/total PSA ratio (f/tPSA%) wasinformative and independent in predicting the presence of PCa, consideringthat for high values of this percentage (17%) the probability of finding PCadecreased. Receiver operating characteristics areas under the curve (AUC)for IGF1 and IGFBP3 were not informative (AUC ~0.5 in both cases) contraryto the AUC for f/tPSA% (AUC = 0.689, p = 0.0002). Conclusions The present study showed that neither IGF1 and IGFBP3 alone nor incombination with PSA enhance the diagnostic performance of PSA in PCa.
Background: Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. Methods: The analytical and clinical performance of the Access OV Monitor Immunoassay System ...(Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD+8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycerides 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R=0.982, slope=0.921, intercept=+1.951). OV Monitor serum levels were low in healthy individuals (n=267, median=9.7 kU/L, 95th percentile=30.8 kU/L), higher in individuals with various benign diseases (n=549, medians=10.9–16.4 kU/L, 95th percentiles=44.2–355 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=12.4–445 kU/L; 95th percentiles=53.4–4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer area under the curve (AUC) 0.898. Results for the reference CA125 assay were comparable (AUC 0.899). Conclusions: The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers. Clin Chem Lab Med 2008;46:588–99.
Background: Cancer antigen CA15-3 antigen is known as a valuable marker for the management of breast cancer. Methods: The analytical and clinical performance of the Access® BR Monitor Immunoassay ...System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA15-3 on the Elecsys® System (Roche Diagnostics). Results: Total imprecision (%CV) of the BR Monitor ranged between 5.5% and 11.7%, and inter-laboratory reproducibility between 3.4% and 5.1%. Linearity upon dilution showed a mean recovery of 98.5% (SD±9.1%). Endogenous interferents had no influence on BR Monitor levels (mean recoveries: hemoglobin 112%, bilirubin 111%, triglycerides 108%). There was no high-dose hook effect up to 13,540 kU/L. Clinical performance investigated in sera from 1811 individuals showed a general correlation between the Access BR Monitor and Elecsys CA15-3 (R=0.797), with a slope of 1.383. CA15-3 serum levels, as measured by the BR Monitor, were low in healthy individuals (n=267, median=11.9 kU/L, 95th percentile=23.5 kU/L), higher in individuals with various benign diseases (n=549, medians=11.3–15.6 kU/L, 95th percentiles=21.6–54.6 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=11.2–22.8 kU/L, 95th percentiles=30.0–429.7 kU/L). Best diagnostic accuracy for cancer detection against the relevant benign control group by the BR Monitor was found for locoregional and metastatic breast cancer, as well as for ovarian cancer area under the curve (AUC) 0.619, 0.897 and 0.774. Results for the reference CA15-3 assay were comparable (AUC 0.611, 0.887 and 0.818). Conclusions: The Access BR Monitor provides accurate methodological characteristics and demonstrates an analytical and clinical correlation with Elecsys CA15-3. Best diagnostic accuracy for the BR Monitor was found in breast and ovarian cancer. Our results also suggest a clinical value of the BR Monitor in other cancers. Clin Chem Lab Med 2008;46:612–22.
To further investigate the role of sex hormones in breast cancer, we assessed the relations of circulating estradiol and testosterone to tumor size and estrogen receptor (ER) status.
This was a ...cross-sectional study including 492 postmenopausal breast cancer patients. The relation of circulating hormones to patient and tumor characteristics was assessed using the Fisher or Cuzick tests. Multivariable logistic regression was used to estimate the odds ratios (ORs) of having tumors =2 cm (vs and <2 cm) and having ER-positive tumors (vs ER-negative) with increasing quartiles of estradiol and testosterone.
Mean estradiol and testosterone levels increased significantly with increasing tumor size. The ORs of tumors =2 cm increased significantly with increasing quartiles of estradiol (Ptrend and <0.001) and testosterone (Ptrend=0.005). When adjusted for estradiol, the association between testosterone and tumor size was no longer significant. Mean testosterone levels were higher in ER-positive than ER-negative patients (p and <0.001), while mean estradiol levels did not differ significantly between the two ER categories (p=0.192). The ORs of having an ER-positive tumor increased significantly with increasing quartiles of testosterone (Ptrend=0.002), whereas the increase with increasing estradiol quartiles was not significant (Ptrend=0.07).
The association of both hormones with tumor size implies that both are involved in tumor growth, testosterone mainly by conversion to estradiol. The strong association of testosterone with ER contrasts with the weak association of estradiol with ER and confirms testosterone as a marker of hormone-dependent tumors. These findings suggest that testosterone evaluation might be useful to better identify patients with hormone-dependent disease.
Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access® ...GI Monitor assay (Beckman Coulter) was evaluated on the UniCel® DxI 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access® GI Monitor and Elecsys CA19-9 (R=0.959, slope=1.004, intercept=+0.17). GI Monitor serum levels were low in healthy individuals (n=267, median=6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n=550, medians=5.8–13.4 kU/L, 95th percentiles=30.1–195.5kU/L) and even higher in individuals suffering from various cancers (n=995, medians=8.4–233.8 kU/L, 95th percentiles=53.7–13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer area under the curve (AUC) 0.83. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access® GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers. Clin Chem Lab Med 2008;46:600–11.
Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer.
The analytical and clinical performance of the Access GI Monitor assay ...(Beckman Coulter) was evaluated on the UniCel Dxl 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics).
Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD + 7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access GI Monitor and Elecsys CA19-9 (R = 0.959, slope = 1.004, intercept = +0.17). GI Monitor serum levels were low in healthy individuals (n = 267, median = 6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n = 550, medians = 5.8-13.4 kU/L, 95th percentiles = 30.1-195.5 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 8.4-233.8 kU/L, 95th percentiles = 53.7-13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer area under the curve (AUC) 0.83. Results for the reference CA19-9 assay were comparable (AUC 0.85).
The Access GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers.
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