Surfaced-Enhanced Laser Desorption/Ionization Time-of-Flight (SELDI-TOF) Differentiation of Serum Protein Profiles of BRCA-1 and Sporadic Breast Cancer

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Abstract
Background: BRCA-1 mutations predispose women to early onset breast cancer, but ∼20% never develop cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) profiling can differentiate protein signatures of cancer and normal subjects. Our objective was to distinguish women with BRCA-1 mutations who developed breast cancer (BRCA-1 Ca) from those who did not (Carrier), normal volunteers (NL), and women with sporadic breast cancer (SBC), using SELDI-TOF. Methods: Baseline serum specimens were obtained from women with BRCA-1 mutations without cancer, SBC, and NL. BRCA-1 women were later divided into two cohorts, pending cancer development. The sera were spotted onto protein chips for SELDI-TOF analysis and analyzed with classification algorithm software. Results: BRCA-1 Ca patients (n = 15) developed cancer within 3 years of baseline, while BRCA-1 carriers (n = 15) were cancer-free in 7 years of follow-up. SELDI-TOF analysis revealed differentially expressed proteins (P < .05) between BRCA-1 Ca, Carrier, and SBC patients (n = 16), such that 13/15 BRCA-1 Ca vs. Carrier women were correctly identified (sensitivity/specificity of 87%/87%) and 14/15 BRCA-1 Ca vs. SBC patients were correctly identified (sensitivity/specificity 94%/100%). Profiles of Carriers resembled NL profiles (n = 16). Conclusions: SELDI-TOF protein profiles from this small pilot study distinguished between women with BRCA-1 Ca, Carriers, and women with SBC. Whether BRCA-1 Ca represents earlier detection of occult cancer or other risk factors is unknown. Follow-up studies with larger numbers and longer follow-up are required to validate these findings but may allow more timely prophylactic or therapeutic strategies.