Search

To date, lateral differences of invasive breast cancer (IBrC) with respect to the angiogenic and hemostatic profiles were never studied. Here, we aimed to determine the relationship of tumor laterality with various clinical and pathological parameters including angiogenic and hemostatic profiles. A total of 92 women that were initially non-metastatic and treated by surgery were included in this single-center prospective study. Patients were grouped according to tumor localization. A four-year follow-up was accomplished in all patients with a 15.22% recurrence rate. An immunoassay of selected angiogenic and hemostatic parameters, as well as immunohistochemistry of estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki67, was comparatively performed in groups with right- and left-sided IBrC. The same analysis was carried out in a subgroup of patients with luminal A molecular subtype of cancer. Patients with right-sided tumors free of nodal involvement had a significantly longer overall survival compared to their left-sided counterparts ( p = 0.0491). Additionally, right-sided tumors had a higher predisposition to be a luminal-A subtype of IBrC ( p = 0.0016). Furthermore, 10% of left-sided tumors exhibited an overexpression of HER2, while only 2% patients suffering right-sided tumors displayed a positive score ( p = 0.0357). Our findings revealed a significantly higher concentration of vascular endothelial growth factor (VEGF)-A ( p = 0.0136), lower anti-angiogenic ratios (sVEGFR1/VEGF-A ( p = 0.0208) and sVEGFR2/VEGF-A ( p = 0.0068)), and elevated plasminogen activator inhibitor type 1 (PAI-1) ( p = 0.0229) in patients with breast cancer localized in the left breast, regardless of the molecular subtype of IBrC. Our study showed that left-sided breast tumors without lymph node metastases demonstrate worse overall survival. Laterality of IBrC is associated with pro-angiogenic and pro-thrombotic conditions. We propose to consider laterality as a prognostic factor of IBrC.

The metabolism of alkylating agents is accompanied by the generation of reactive oxygen species. The aim of this study was to treat estrogen receptor-positive and estrogen receptor-negative human breast cancer cells, MCF-7 and MDA-MB-231, respectively, with cisplatin and five different berenil-platinum (II) complexes, and then to investigate the oxidative modifications of DNA, lipid and protein, and to compare them with the profile of various pro- and antiapoptotic proteins. Changes in the levels of 8-hydroxy-2'-deoxyguanosine, 4-hydroxynonenal, carbonyl groups, dityrosine, active caspases 3, 8 and 9, as well as the expression of Bcl-2, Bax, cytochrome c, and p53 were subsequently examined. Activities of superoxide dismutase, catalase and glutathione, vitamin C levels were also investigated. Cellular reactions to cisplatin and the berenil-platinum (II) derivatives were more pronounced in MCF-7 cells as compared with the MDA-MB231 cells. Furthermore, the berenil-platinum (II) derivatives were found to be more effective than cisplatin. All of the complexes reduced the activity of superoxide dismutase and catalase, and also lowered the levels of non-enzymatic antioxidants. Increased level of lipid, protein as well as DNA damage markers was also observed after berenil-platinum (II) derivatives treatment. Similarly, the increase in the levels of the proapoptotic factors, were detected in MCF-7 and MDA-MB231 cells. Incubation of examined cells with the berenil-platinum (II) complexes also led to the increase in the levels of active caspases 3, 8 and 9. In conclusion, the results of the present study demonstrated that berenil-platinum (II) complexes more efficiently mediate cellular oxidative modifications and proapoptotic metabolism, particularly in MCF-7 cells, compared to cisplatin. Pt2(isopropylamine)4berenil2 and Pt2(piperidine)4(berenil)2 notably affected the cellular metabolism of estrogen-positive breast cancer cells. Thus, these complexes may be valuable for the design of additional anticancer drugs.