Prognostic significance of plasma osteopontin level in breast cancer patients

Abstract

Abstract Many studies have demonstrated that osteopontin (OPN) contributes functionally to aggressive behaviour in many tumours including breast cancer. This study aims to investigate its role as a simple biochemical marker easily measured in plasma of breast cancer patients to give an early signal for metastases and to detect its relationship to clinicopathological findings and survival. We measured plasma OPN, CA15.3 and serum alkaline phosphatase (ALP) activity in 55 patients, 28 with early stage breast cancer and 27 with bone metastasis out of whom 20 had metastasis in other sites. The median age at diagnosis for non-metastatic cases was 60 years (range 35-85) and for metastatic cases was 45.5 years (range 32-59). In the non-metastatic group, 78.57% of the patients were histologically graded as grades I and II and 21.43% as grade III tumours. In the metastatic group, 81.48% of the patients had grades I and II and 18.52% had grade III tumours; 54% of patients in the non-metastatic group were at stage II and 46% were at stage III at presentation. All patients of group II had bone metastasis, 33% had liver metastases, 25.9% had lung metastasis and 14.8% had lymph node metastasis. Patients with non-metastatic disease had a median OPN level of 55 ng/ml (range 54-150 ng/l), while those in the metastatic group had a median of 148.0 ng/l (range 56.0-156.0 ng/l), a difference which was statistically significant (P = 0.001). There was no statistically significant difference in the median levels of CA15.3 and ALP between both groups. The median OPN level was significantly higher with serum ALP level above 90, progesterone receptor (PR) status, bone and visceral metastasis. Median OPN was not affected significantly by menopausal status (P-value 0.3), tumour grade (P-value 0.3), estrogen receptor (ER) status (P-value 0.7), pathological type (P-value 0.42) or serum CA15.3 level (P-value 0.6). At the end of 12-year follow-up, 83% of the patients survived (92.3% in the non-metastatic versus 74.1% in the metastatic group). The estimated median survival for the whole study population at 12 years was 13 years (95% CI 8.144-17.856). The estimated median survival was 13 years (95% CI 0) and 12 years (95% CI 4.893-19.11) in patients with median OPN levels of <142 and ≥142, respectively, a difference which was not statistically significant (P = 0.343). No statistically significant difference in overall survival OS was noticed in relation to menopausal status (P = 0.7), pathological type (P = 0.4) and hormone receptor status (P = 0.3). At 6-year follow-up, it was found that OS was affected by the presence of visceral metastasis, tumour grade, serum plasma level of ALP and the serum level of CA15.3 (P = 0.0006, 0.007, 0.001 and 0.03, respectively). However, the presence of bone metastasis did not affect OS (P = 0.6). Osteopontin level can be a simple biochemical marker easily measured in plasma of breast cancer patients to give early signals for metastases, but not a prognostic factor for survival.