Osteopontin level and promoter polymorphism in patients with metastatic breast cancer

Cancer initiation typically occurs when a proto-oncogene's coding region undergoes mutation, resulting in uncontrollable cell growth and division, or when a tumour suppressor gene's coding region is affected by a mutation that inhibits activity of the resulting gene product. The pathophysiologic result is, respectively, exaggerated cell-cycle growth or deficient programmed cell death. Osteopontin (opn) is an integrin-binding phosphoprotein that is expressed on the surface of normal cells. Osteopontin has a major role in diverse tumour components, especially those implicated in invasion and metastasis. In the present study, we aimed to illustrate the value of opn as a possible contributor in breast cancer (bca). This prospective study included 115 patients newly diagnosed with bca and distant metastasis who were recruited from the Oncology Center, Mansoura University, and the Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Egypt. The patients recruited had been diagnosed with disseminated visceral metastasis (visceral crisis), with or without bone metastasis; patients with cranial metastasis were excluded from the study. All patients received first-line chemotherapy with docetaxel 75 mg/m plus cisplatin 75 mg/m or carboplatin 6 auc (area under the curve) on day 1 every 21 days for a maximum of 6 cycles or till development of toxicity. Trastuzumab (in cases of her2-positive disease) was given whenever possible (if government assistance or personal finances permitted). Serum levels of opn were assessed by enzyme-linked immunosorbent assay (elisa) before treatment was started. A group of 30 matched healthy women whose median serum opn level was 15 ng/dL were included, and that level was therefore defined as the cut-off value. In addition, opn gene mutation was determined by polymerase chain reaction (pcr). Correlations of pretreatment serum opn and opn gene mutation with various patient clinicopathologic variables, response to the treatment, progression-free survival (pfs), and overall survival (os) were assessed. Mean serum opn was highest in her2-amplified bca (64.4 ± 42.3 ng/dL), and then in triple-negative bca (55.9 ± 34.7 ng/dL), followed by the luminal B and A subtypes (38.4 ± 33.1 ng/dL and 36.3 ± 32.2 ng/dL respectively, = 0.017). Testing by pcr revealed that opn gene mutation was highest in triple-negative bca (85% opn mutant vs. 15% non-mutant), and then in her2-overexpressed bca (80% opn mutant vs. 20% non-mutant)