Abstract
This study investigates whether a set of ten potential breast cancer serum biomarkers and cancer antigens (osteopontin (OPN), haptoglobin, cancer antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), prolactin, cancer antigen 19-9 (CA19-9), α-fetoprotein (AFP), leptin and migration inhibitory factor (MIF)) can predict early stage breast cancer in samples collected before clinical diagnosis (phase III samples). We performed a nested case-control study within the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. We examined to what extent the biomarker panel could discriminate between 68 women diagnosed with breast cancer up to three years after enrollment and 68 matched healthy controls (all 56–64 years at baseline). Using a quantitative bead-based multiplexed assay, we determined protein concentrations in serum samples collected at enrollment. Principal Component Analysis (PCA) and Random Forest (RF) analysis revealed that on the basis of all ten proteins, early cases could not be separated from controls. When we combined serum protein concentrations and subject characteristics related to breast cancer risk in the RF analysis, this did not result in classification accuracy scores that could correctly classify the samples (sensitivity: 50%, specificity: 50%). Our findings indicate that this panel of selected tumor markers cannot be used for diagnosis of early breast cancer.
Highlights
The identification of blood biomarkers for early detection of breast cancer is an important target of research
We investigated the discriminative value of this serum tumor marker panel in a nested case-control study within the Prospect-EPIC
Using a serum panel of potential breast cancer markers consisting of OPN, haptoglobin, cancer antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), prolactin, cancer antigen 19-9 (CA19-9), AFP, leptin and migration inhibitory factor (MIF), we were unable to predict the presence of early stage breast cancer
Summary
The identification of blood biomarkers for early detection of breast cancer is an important target of research. A blood test would be easy to perform and would omit the imaging-related problem of high breast density [1] As such, it would offer potential for younger women, who are excluded from most breast cancer screening programs, mainly because the prevalence of dense breast tissue is very high in this group. Researchers have identified many substances that seem to be differentially expressed in blood when certain types of cancer are present [2] These substances, or cancer biomarkers, are mainly tested for use in monitoring, i.e., following whether the cancer is in regression due to the anti-cancer treatment, or monitoring whether the cancer is re-occurring, rather than for early cancer detection. The utility of available biomarkers for cancer screening is unknown
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