Correlation of breast cancer risk factors with HER-2/neu protein overexpression according to menopausal and estrogen receptor status

BACKGROUND: Several researchers have claimed that classification of tumours on the basis of HER-2/neu overexpression or amplification may define a subset of breast cancer in which the net effect of a risk factor could be rather more obvious and its impact on breast cancer development more clear. We decided to investigate, in a group of patients from a geographical area with a low incidence of breast cancer, whether HER-2/neu positive tumours are correlated with established or suspected risk factors for breast cancer and thus to identify distinct subgroups of high risk women. METHODS: This study analysed data from patients who attended the Breast Unit at the University Hospital of Heraklion, Crete, Greece between 1996 and 2002. 384 women with primary invasive breast cancer were compared with 566 screened women who were referred to the Unit and had not developed breast neoplasm by the time the data were analysed. Risk factor data were obtained from each subject by personal interviews using a structured questionnaire. The detection and scoring of the HER-2/neu protein, estrogen and progesterone receptor expression were performed using immunochemistry. Odds ratios and 95% confidence intervals were determined by chi-square test and logistic regression analysis. Case-case odds ratios were calculated in order to measure the risk heterogeneity between HER-2/neu+ and HER-2/neu-tumours. Separate analyses were performed for premenopausal and postmenopausal women and according to estrogen receptor status. RESULTS: In multivariate analysis without HER-2/neu stratification, an increased breast cancer risk was associated with only four of the factors examined: use of oral contraceptives (OR = 4.40, 95%C.I: 1.46–13.28), use of HRT (OR = 7.34, 95%C.I: 2.03–26.53), an age at first full pregnancy more than 23 years (OR = 1.91, 95%C.I: 1.29–2.83) and body mass index more than 29 kg/m(2 )(OR = 3.13, 95%C.I: 2.02–4.84). Additionally, a history of abortion or miscarriage (OR = 0.56, 95%C.I: 0.38–0.82) was correlated with a decreased risk of breast cancer. In the case to case comparison only BMI >29 kg/m(2 )revealed a relative connection that was stronger with positive than with negative HER-2/neu tumours (ratio of OR's = 2.23, 95%C.I: 1.20–4.15, p = 0.011). This may indicate evidence of heterogeneity of a rather significant degree for this factor. In the ER negative group an age at first full pregnancy >23 years and a BMI >29 kg/m(2 )were associated with an increased risk in both HER-2/neu groups, but the association was significantly stronger for the latter factor in the positive HER-2/neu tumours (ratio of OR's = 2.46, 95%CI: 0.97–6.21). CONCLUSIONS: Our study did not confirm that the established or putative hormonal breast cancer risk factors differ regarding their relations with HER-2/neu+ versus HER-2/neu-breast tumours, with the exception of increased BMI. Further innovative studies with larger sample sizes are needed to examine how the status of these potentially modifiable breast cancer risk factors interacts with biological markers such as HER-2/neu oncoprotein

On the distribution of quadratic forms and applications in the analysis of repeated measurements

In this paper a unified approach is given to the distribution of scalar quadratic forms for dependent variables. Necessary and sufficient conditions are found for the sums of squares of the various hierarchical layers in ANOVA to be distributed as multiples of chi-square variables. Results concerning the usual univariate F-tests in ANOVA of repeated measurements are derived as a special case.27112625264

Significance of alpha-2-macroglobulin, alpha-1-acid glycoprotein, and C-reactive protein in pleural effusion differentiation

Background: The differentiation between exudates and transudates is fundamental when investigating the cause of pleural effusions. Acute-phase proteins could be potentially useful markers in this discrimination. Objective: The present study was designed to evaluate whether the acute-phase proteins: alpha(2)-macroglobulin (AMG), alpha(1)-acid glycoprotein (AAG) and C-reactive protein (CRP) are useful in investigating the pleural effusions. Methods:We prospectively measured the concentrations of the above proteins in the serum and pleural fluid of 84 consecutive patients with various diseases using a nephelometric assay. Results: Pleural effusion AMG, AAG and CRP were all significantly elevated in the group of patients with exudates compared to patients with transudates (p < 0.001, p < 0.001 and p < 0.01, respectively). An AAG value >63 mg/dl in a pleural effusion is predictive of an exudate with a sensitivity of 90% and a specificity 85%. Similarly, an AMG value >44 mg/dl in a pleural effusion is predictive of an exudate with a sensitivity and a specificity of 90% and 60%, respectively. Moreover, pleural AAG was significantly higher in cancerous exudates than in exudates and transudates of all other cause taken together (p < 0.001). Finally, to differentiate the same pleural effusion, the cut-off value of 1.0 mg/dl of pleural CRP has a sensitivity and a specificity of 74% and 74%, respectively. Conclusions: We conclude that both AAG and AMG concentrations in pleural effusions have a high sensitivity and are therefore useful parameters in distinguishing exudates from transudates, but the latter is inferior due to its unacceptably low specificity. Copyright (C) 2000 S. Karger AG, Basel