Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES Is Consistently Increased

Abstract

Background Current biomarkers for breast cancer have little potential for detection. We determined if breast cancer subtypes influence circulating protein biomarkers. Methods A sandwich-ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated based on breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses. Results Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P<0.01 for each analysis) in all four subtypes, with areas under receiver operating characteristic curves (AUC) that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets. Conclusions Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true and false positive screens for breast cancer. Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods.

Circulating levels of angiogenesis-related growth factors in breast cancer: A study to profile proteins responsible for tubule formation

“…Many studies have measured the production of angiogenesis-related factors in serum from women with breast cancer via ELISA analysis; however, the majority of these have only examined one or two angiogenesisrelated factors, including VEGF (6,8,19,20), basic FGF (6), IL-6 (21), leptin and prolactin (8) and thrombospondin-1 (19). To date, there have only been three studies which have looked at the expression of multiple angiogenic factors in serum from women with breast cancer (10,12,22).…”

“…The process of angiogenesis is not the result of one single growth factor but rather is dependent on the interaction of multiple proteins with pro-or antiangiogenic properties. In breast cancer, like almost all other solid tumours, growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), hepatocyte growth factor (HGF), platelet derived growth factor (PDGF), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1β, interleukin (IL)-8 and the regulated on activation, normal T cell expressed and secreted (RANTES), are expressed and, depending on Circulating levels of angiogenesis-related growth factors in breast cancer: A study to profile proteins responsible for tubule formation the subtype of breast cancer, have been identified as negative prognostic factors for patient survival (6)(7)(8)(9)(10). These growth factors may be responsible for inducing angiogenesis as they are pro-angiogenic, however, breast cancer cells and tissues can also produce inhibitors of angiogenesis, including thrombospondin, angiostatin and endostatin (11).…”

“…This evidence directs further investigation into the importance of assessing the roles and levels of angiogenic factors in plasma from women with and without breast cancer. However, despite numerous studies into the detection of circulating biomarkers in breast cancer patients (9,10,12,13), the molecular mechanism(s) by which these circulating factors present in breast cancer may contribute to, and influence angiogenesis, are still poorly understood, suggesting a complex mechanism of interactions. Therefore, the aim of the present study was to assess the ability of circulating factors, present in the plasma from women with breast cancer, to influence tubule formation in an in vitro system (14) and to identify key factors responsible for increased angiogenesis.…”

Chemokines and Bone

“…CCL5 can be expressed and secreted either by cancer cells or by non-malignant stromal cells in the microenvironment. Investigations have indicated that CCL5 expression correlates with advanced BC, with greater plasma levels being found in patients with progressive and more advanced disease than those in remission [138]. Correspondingly, CCR5 expression is prerequisite for the induction of metalloproteinases by CCL5 in BC cells, thereby contributing to their invasive nature [139].…”

Photonic crystal enhanced fluorescence for early breast cancer biomarker detection

“…Our data suggest that the use of biomarker assays as an early-stage diagnostic test have been problematic due to the phenotypic diversity of breast cancer [12]. That is, five major subtypes of breast cancer have been identified based on both gene expression and protein profiles in tumor tissue [13–17], and these profiles are closely associated with traditional histological classifiers related to the overexpression of estrogen receptor (ER+) and/or the HER2 receptor (HER2+) [15, 18].…”