Serial Plasma Osteopontin Levels Have Prognostic Value in Metastatic Breast Cancer

Abstract

Purpose: Osteopontin is a malignancy-associated protein measurable in blood and tumor tissue.To evaluate its prognostic value in advanced disease, we conducted a prospective clinical study measuring serial osteopontin plasma levels in women with metastatic breast cancer throughout the course of their disease. Experimental Design: One hundred fifty-eight women with newly diagnosed metastatic breast cancer were enrolled in the study. Plasma osteopontin was measured using our validated ELISA, at baseline and every 3 to 12 weeks during and after therapy until death. Multivariate timedependent survival analyses were conducted using models that right censored patient outcomes 3, 6, and 12 months after the last known osteopontin measurement. Results: Osteopontin was measured in 1,378 samples (median, 9 per patient). Ninety-nine patients had elevated baseline osteopontin (median, 177 ng/mL; range, 1-2,648 ng/mL). In univariate analysis, elevated baseline osteopontin was associated with short survival (P = 0.02). In a multivariate model incorporating standard prognostic factors, baseline osteopontin was significantly associated with survival duration (relative risk, 1.001; P = 0.038). Metastasis-free interval, visceral metastases, and Eastern Cooperative Oncology Group status 2 to 4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential osteopontin levels, an osteopontin increase of >250 ng/mL at any time was the variable with the most prognostic value for poor survival (relative risk, 3.26; P = 0.0003), and poor Eastern Cooperative Oncology Group status also retained significance. Conclusions: This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.Remarkable progress has been made in elucidating the genetics and molecular biology of breast cancer. Since the early 1990s, there are clear indications of a trend toward decreased breast cancer mortality, mainly attributable to mammography screening and better treatments for early breast cancer (1, 2).Unfortunately, many women still go on to develop distant metastases, which are the leading cause of death.Multiple systemic therapies are now available for women with metastatic breast cancer. These do not cure the disease but are often used in sequence to improve symptoms and prolong survival while maintaining maximal quality of life. Clinical features of the disease (short disease-free interval, visceral disease, large tumor burden, lack of response to prior therapy) are most often used to forecast aggressive tumor behavior (3,4). In this setting, early, intensive chemotherapy, and/or novel treatments, possibly accompanied by greater toxicities, may be indicated. Markers assayed in the primary tumor, such as estrogen and progesterone receptors and HER-2/neu, have prognostic and predictive value (3, 4)...

Osteopontin but not osteonectin favors the metastatic growth of pancreatic cancer cell lines

“…[43][44][45][46][47][48][49] Parallel to upregulated expression in tumor tissues, elevated OPN plasma levels seem to be a marker for metastatic progression and poor survival in patients with cervix, breast, prostate and pancreatic cancers. 47,[50][51][52][53][54] We found a 2.2-fold and 1.6-fold increase in OPN mRNA in pancreatic cancer and chronic pancreatitis samples, respectively, compared to normal pancreatic tissues. 9 The observed upregulation of both, ON and OPN in PDAC hints to a causal involvement of the two proteins.…”

Prognostic Value of Osteopontin in Patients Treated with Primary Radiotherapy for Head and Neck Cancer

“…Increased OPN expression is responsible for shorter survival in breast, prostate and gastric cancers (Bramwell et al, 2006;Wu et al, 2007;Vergis et al, 2008). However, the number of clinical studies investigating the efficacy of OPN in SCHNC cases is limited (Lu et al, 2011).…”

Microdialysis Combined with Proteomics for Protein Identification in Breast Tumor Microenvironment In Vivo

“…Accordingly, OPN was found to be significantly higher in the sera of PyVmT mice when compared to controls. For women with metastatic breast cancer, higher expression of plasma OPN (>123 ng/mL) was also found to be significantly associated with poor prognosis [75]. Furthermore, other proteins identified in the tumor microdialysis perfusates, such as cathepsin B and cystatin C, have been suggested as prognostic biomarkers in the sera of patients with early-stage and inflammatory breast cancer [76].…”