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Mediation analysis allows the examination of effects of a third variable in the pathway between an exposure and an outcome. The general multiple mediation analysis method, proposed by Yu et al, improves traditional methods (eg, estimation of natural and controlled direct effects) to enable consideration of multiple mediators/confounders simultaneously and the use of linear and nonlinear predictive models for estimating mediation/confounding effects. In this paper, we extend the method for time-to-event outcomes and apply the method to explore the racial disparity in breast cancer survivals. Breast cancer is the most common cancer and the second leading cause of cancer death among women of all races. Despite improvement of survival rates of breast cancer in the US, a significant difference between white and black women remains. Previous studies have found that more advanced and aggressive tumors and less than optimal treatment may explain the lower survival rates for black women as compared to white women. Due to limitations of current analytic methods and the lack of comprehensive data sets, researchers have not been able to differentiate the relative effect each factor contributes to the overall racial disparity. We use the CDC-funded Patterns of Care study to examine the determinants of racial disparities in breast cancer survival using a novel multiple mediation analysis. Using the proposed method, we applied the Cox hazard model and multiple additive regression trees as predictive models and found that all racial disparity in survival among Louisiana breast cancer patients were explained by factors included in the study. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most frequent localization of malignant process in American women and women of European countries. To date it is not possible to control the morbidity growth due to lack of effective ways of primary prevention. Comparing the incidence of breast cancer in developed countries with the countries of Asia and Africa, there is the fact of population predominance lesion in more urbanized countries. This suggests that the environment along with other factors, occupies a significant place in the initiation and progression of breast neoplasia. The impressive rates of industrial development led to the pollution of soil, surface water and, as a consequence, food by heavy metal salts. The purposes of this paper are as follows: the chemical composition determination of neoplastic breast tissue, evaluation of the DNA methylation level, study of prognostic-important receptors expression in the breast cancer cells, establishing linkages between all the derived indicators. Methods: In our study we used the following methods: studying of the chemical composition of breast cancer tissue by atomic absorption spectrophotometry and energy-dispersion spectrometer; immunohistochemical study of ER, PR, HER2/neu, p53, Ki-67, E-cadherin and MGMT receptors; DNA extraction and investigation by oscillating infrared spectroscopy method. Results: The total amount of heavy metals in breast cancer tissue ranged from 51.21 x 10-3 to 84.86 x 10-3 µg/kg. We have got the following results: the growth of heavy metals in neoplastic tissue is accompanied with the increase of HER2/neu, p53, Ki-67, MGMT expression and decrease of ER and PR expression. The increment of pathological DNA methylation is accompanied with the increasing amount of heavy metals in tumor tissue. Conclusions: Heavy metals through different pathogenetic links stimulate the progression of breast cancer and reduce its sensitivity to treatment. DNA of tumor tissue has a different level of methylation which changes with the amount of heavy metals in cancer cells. This is displayed on the synthesis of prognostically important receptors in neoplastic tissue. [ABSTRACT FROM AUTHOR]