A multiparametric serum marker panel as a complementary test to mammography for the diagnosis of node-negative early-stage breast cancer and DCIS in young women.

Abstract

BACKGROUND:

The sensitivity of mammography for the detection of small lesions, including node-negative early-stage (T1N0) primary breast cancer (PBC) and ductal carcinoma in situ (DCIS), is significantly decreased in young patients. From a clinical standpoint, an inconclusive mammogram reflects the inability of clinicians to confidently decide whether patients should be referred for biopsy or for follow-up with repeat imaging.

METHODS:

Specific ELISAs were developed for a panel of 13 well-recognized breast autoantigens (HSP60, FKBP52, PRDX2, PPIA, MUC1, GAL3, PAK2, P53, CCNB1, PHB2, RACK1, RUVBL1, and HER2). Circulating autoantibody levels were measured in a cohort of 396 serum samples from histologically confirmed DCIS (n = 87) or T1N0 PBC (n = 153) and healthy controls (n = 156).

RESULTS:

Individually, antibodies against CCNB1, FKBP52, GAL3, PAK2, PRDX2, PPIA, P53, and MUC1 demonstrated discriminatory power between breast cancer and healthy control groups. At 90% sensitivity, the overall combined specificity of the autoantibody serum screening test was 42%. Adjustment for higher sensitivities of 95% and 99% resulted in 30% and 21% specificities, respectively (33% and 18% in T1N0 PBC and 28% and 21% in DCIS). Finally, in patients with node-negative early-stage breast cancer younger than 50 years, the autoantibody assay exhibited 59% specificity with a fixed sensitivity at 90%.

CONCLUSIONS:

Our autoantibody panel allows accurate detection of early breast cancer and DCIS, notably in younger patients.

IMPACT:

Clinical assessment of this autoantibody panel displays a potential to facilitate clinical management of early-stage breast cancer detection in cases of inconclusive mammogram.

• Authors: Jérôme Lacombe, Alain Mangé, Anne-Claire Bougnoux, Ioannis Prassas, Jérôme Solassol
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 23 Issue 9 Pg. 1834-42 (Sep 2014) ISSN: 1538-7755 [Electronic] United States
• PMID: 24957886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Autoantibodies
• Biomarkers, Tumor
• PHB2 protein, human
• Prohibitins

Topics

• Adult
• Aged
• Autoantibodies (blood)
• Biomarkers, Tumor (blood)
• Breast Neoplasms (blood, diagnosis, diagnostic imaging, pathology)
• Carcinoma, Intraductal, Noninfiltrating (blood, diagnosis, diagnostic imaging, pathology)
• Early Detection of Cancer
• Female
• Humans
• Lymphatic Metastasis
• Mammography
• Middle Aged
• Prohibitins