Identification and validation of new autoantibodies for the diagnosis of DCIS and node negative early-stage breast cancers.

Evidence of circulating autoantibodies in cancer patient sera has created opportunities for exploiting them as biomarkers. We report the identification and the clinical validation of an autoantibody panel in newly diagnosed patients with early-stage breast cancer. Proteomic approach and serological screening of a discovery set of sera (n = 80) were performed to identify tumor-associated antigens (TAAs). Autoantibody levels were then measured in an independent validation set (n = 182) against a panel of five TAAs by enzyme-linked immunosorbent assay. Sixty-seven antigens that elicited a specific humoral response in breast cancer were identified and five antigens (GAL3, PAK2, PHB2, RACK1 and RUVBL1) were selected for validation. GAL3 and RACK1 showed significantly increased reactivity in early-stage breast cancer. When combined, the five markers significantly discriminated early-stage cancer from healthy individuals (AUC = 0.81; 95% CI [0.74-0.86]). Interestingly, this value was high in both node-negative early-stage primary breast cancer (AUC = 0.81; 95% CI [0.72-0.88]) and ductal carcinoma in situ (AUC = 0.85; 95% CI [0.76-0.95]) populations. This autoantibody panel could be useful as a diagnostic tool in a screening strategy of early-stage invasive breast cancer and preinvasive breast cancer. It could be particularly appropriate in complement to mammography for women with high breast density.

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