Validation of plasma proneurotensin as a novel biomarker for the prediction of incident breast cancer.

Abstract

High fasting plasma proneurotensin concentration was associated with the development of breast cancer in the Malmö Diet and Cancer Study (MDCS). Here, we aimed at replicating the initial finding in an independent second cohort. The Malmö Preventive Project (MPP) is a population study and comprised 18,240 subjects when examined in 2002-2006. Of women without history of breast cancer at examination, we included all who developed breast cancer during follow-up (n = 130) until December 31, 2010, and a random sample of women without breast cancer until the end of follow-up (n = 1,439) for baseline plasma proneurotensin assessment (mean age, 70.0 ± 4.4 years). Proneurotensin was measured in fasting plasma samples and was related to the risk of later breast cancer development using multivariate logistic regression. Proneurotensin [odds ratio (OR) per standard deviation (SD) increment of LN-transformed proneurotensin] was significantly related to incident breast cancer [OR, 2.09; 95% confidence interval (CI), 1.79-2.44; P < 0.001; adjusted for age, body mass index (BMI), smoking, and hormone replacement therapy]. The effect estimate in the MPP was larger than in the discovery cohort (MDCS), with the main difference between the two cohorts being that women of the MPP study were on the average about 10 years older and follow-up time was shorter than that of the MDCS. As initially found in the MDCS, fasting plasma proneurotensin was significantly associated with the development of breast cancer in the MPP study as well. Measurement of plasma proneurotensin warrants further investigation as a blood-based marker for early breast cancer detection.