Abstract P2-14-08: Plasma pro-enkephalin and pro-neurotensin for the risk prediction of incident breast cancer in healthy women

Abstract

Abstract Experimental settings have indicated that Neurotensin regulates both satiety and breast cancer growth. Proneurotensin 1-117 (pro-NT), which stems from the same precursor as Neurotensin, has been developed as a reliable plasma surrogate biomarker for the unstable Neurotensin and has been shown to be associated with the development of incident breast cancer. Enkephalins and related opioid peptides may negatively regulate carcinogenesis and the growth of breast tumors through stimulation of the immune tumor defense system as well as direct inhibitory effects on breast cancer cells. However, little is known about their role in the development of breast cancer in humans. Enkephalin can be assessed in plasma by measuring a stable surrogate marker, Pro-Enkephalin A 119-159 (pro-ENK). OBJECTIVE: To test if plasma pro-ENK in healthy women is associated with the development of incident breast cancer and if it adds information to pro-NT for the risk prediction. DESIGN, SETTING, AND PARTICIPANTS: We measured pro-ENK and pro-NT in fasting plasma from 1929 women (mean age 58 +/- 5.9 years) of the population based Malmo Diet and Cancer Study (MDCS), who were free from breast cancer prior to the baseline exam. We used Cox proportional hazards models to relate pro-ENK and pro-NT to first breast cancer events (n = 123) within 15 years of follow-up. RESULTS: Decreasing concentrations of pro-ENK were significantly associated with the risk of women to develop breast cancer: Women belonging to quartiles 3, 2 and 1 of pro-ENK compared to those of quartile 4 had Hazard ratios (HR) for breast cancer of 1.41 (0.74-2.69), 2.3 (1.27-4.14) and 3.19 (1.82-5.62). Pro-NT: As compared to women belonging to the 1st quartile of pro-NT, women belonging to quartiles 2, 3 and 4 of pro-NT had HRs for the devlopment of breast cancer of 1.24 (0.69-2.24), 1.61 (0.92-2.82) and 2.37 (1.4-4.01). Pro-ENK significantly added prognostic value to pro-NT (p = 0.00006) and vice versa (p = 0.00002). The HR for women with pro-ENK in the 1st quartile and pro-NT in the 4th quartile (high risk group) was 4.17 (2.48-7.03) as compared to women with pro-ENK in quartiles 2-4 and pro-NT in quartiles 1-3 (low risk group). Women with one of the biomarkers in high risk still had a slightly increased risk (HR 1.71 (1.16-2.52)) as compared to the low risk group. CONCLUSION: Biomarker based risk prediction for the development of breast cancer is significantly improved, when plasma pro-ENK is added to pro-NT. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-14-08.