3380 / 8 - Seven autoantibody panel, validated in two independent patient serum collections, can detect women with DCIS and invasive breast cancer

Document Type

Abstract

Publication Date

4-12-2022

Publication Title

AACR American Association for Cancer Research: Annual Meeting 2022

Keywords

oregon; portland; chiles

Abstract

Mammography is essential to identify early breast cancer but the sensitivity is dependent on breast characteristics. A serum-based biomarker used along with mammography to identify lesions that need to be biopsied may improve the sensitivity of mammography and reduce the number of biopsies needed. We have identified a panel of autoantibodies found in early breast cancer. An autoantibody biomarker is ideal because antibody immunity can be detected with very low levels of antigen with direct antigen recognition by B cells resulting in clonal amplification of antigen specific plasma cells. Work in our laboratory has identified tumor-associated proteins present in pre-malignant tumors that are necessary for survival of human breast cancer cells across breast cancer subtypes. Increased autoantibodies to seven of these early tumor-associated proteins (PDIA6, KRT8, SERBP1, ARPC2, RRM2, AURKA, and NDC80) were present in the sera of women with DCIS and invasive breast cancer in two independent serum collections but not in control women with no known breast lesions.
The presence of autoantibodies in the discovery set was evaluated in 185 individuals: 42 control women, 12 women with hyperplasia, 36 patients with fibroadenoma, 59 patients with ductal carcinoma in situ (DCIS), and 36 patients with invasive breast cancer (IBC). The validation set was evaluated in 228 individuals: 50 control patients, 50 patients with fibroadenoma, 18 patients with hyperplasia, 50 patients with DCIS, and 60 patients with IBC, 20 with hormone receptor positive (HR+) HER2 negative, 20 with HER2+, and 20 triple negative (TN). We defined a positive autoantibody response as over 2 standard deviations above the mean found in control women. All seven autoantibodies could predict patients with hyperplasia, fibroadenoma, DCIS, and IBC in both the discovery and validation sets. For example, the seven-antibody panel could identify DCIS from control women with AUC of 0.95 (95% CI 0.912 to 0.995, p<0.0001) and validation set AUC 0.63 (95% CI 0.52 to 0.74, p=0.026). The seven-antibody panel could identify IBC from control women with AUC of 0.85 (95% CI 0.73 to 0.97, p<0.0001) and validation 0.70 (95% CI 0.60 to 0.79, p<0.0001). Furthermore, the seven-antibody panel could identify women with each of the breast cancer subtypes as compared to control women. Women with HR+HER2- breast cancer could be detected with AUC 0.69 (95% CI 0.55 to 0.83 p=0.014), women with HER2+ breast cancer could be detected with AUC 0.69 (95% CI 0.52 to 0.90, p=0.02), and women with triple negative breast cancer could be detected with AUC 0.69 (95% CI 0.55 to 0.83, p=0.002) in the validation set. Future studies will evaluate this panel in a prospective study at the time of mammography to identify a serum biomarker that will improve sensitivity of mammography.

Clinical Institute

Cancer

Department

Earle A. Chiles Research Institute

Department

Oncology

Comments

Sasha Elizabeth Stanton, Jason Schlumbohm, Erik Ramos, Charles Drescher, Jeffrey Marks, Mary L. Disis. Earle A. Chiles Research Insitute, Portland, OR, University of Washington, Seattle, WA, Fred Hutchinson Cancer Research Center, Seattle, WA, Duke University, Durham, NC

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