Analysis of AKR1B10 levels among various groups of breast cancer patients.

Abstract

e14548 Background: Aldo-keto reductase 1B10 (AKR1B10) is a protein that is primarily expressed in human colon and small intestine, but induced in hepatocellular carcinoma and non-small cell lung cancer. Our recent studies have revealed that AKR1B10 is overexpressed in primary, metastatic, and recurrent cancers of the breast. Methods: We recruited four cohorts of patients: Patients with breast cancer undergoing primary surgery from whom we procured breast cancer and matched normal adjacent tissue to evaluate AKR1B10 expression in primary tumors. The matched serum samples were collected before surgery and at various time points after the surgery (approximately 3 days, 7 days, and 1 month Patients with recurrent or advanced (metastatic) breast cancer. Serum samples were collected and serially monitored for up to 2years before and during metastatic therapy and correlated with RECIST measurements. Patients with locally advanced disease undergoing neoadjuvant chemotherapy. AKR1B10 serum levels were monitored during therapy and correlated with RECIST measurements. Healthy individuals with normal mammograms were recruited and submitted serum samples for AKR1B10 serum measurements. Results: AKR1B10 rapidly cleared the serum of early stage breast cancer patients with an estimated half-life of 24-30 hours. Serum AKR1B10 levels correlated strongly with tissue IHC staining and PR positivity but not with RECIST levels or Oncotype Dx scores. Neoadjuvant chemotherapy did not affect serum AKR1B10 levels. Individuals with normal mammograms displayed substantially lower levels of AKR1B10 than breast cancer patients. Patients with DCIS also displayed elevated serum AKR1B10 levels. Conclusions: AKR10 may serve as tumor marker to independently identify high risk patients whose tumors have intermediated risk Oncotype Dx scores and may also identify early breast cancers in patients with equivocal breast biopsies.