Abstract 3730: Timing of prolactin measurement in relation to breast cancer risk
Authors: Tworoger Shelley S. , Eliassen A. Heather , Rosner Bernard A. , Hankinson Susan E. 
Published: June 2012

Abstract
Prolactin is a growth hormone that is associated with breast cancer risk. Since prolactin increases proliferation and cell motility, processes important in later stage tumor development, levels relatively close to diagnosis may be more important for predicting risk. To examine this, we evaluated prolactin levels on samples collected 10 years apart in the Nurses’ Health Study (NHS) with risk of breast cancer to determine if recent versus past levels were more strongly associated with risk. In 1990, 32,826 women gave a blood sample (age 43-70); 18,743 women (ages 53-80 years) gave a second sample in 2000. We measured prolactin on the 1990 blood sample for incident cases diagnosed from 1990-2000 and matched controls and on the 1990 and 2000 (when available) sample for cases diagnosed from 2000-2008 and matched controls. For women without a 2000 sample, we used multiple imputation to estimate their prolactin levels at that time accounting for case status, 1990 prolactin level, and other predictors of prolactin levels (e.g., parity, and menopausal status)(R2=0.17). We calculated relative risks (RR) and 95% confidence intervals (CI) for prolactin levels measured 0-10 years before diagnosis (proximate) and 10-18 years before diagnosis (distant). We compared results from three models using: (1) cases diagnosed from 2000-2008 and their matched controls with prolactin measured in 1990 and 2000 samples, (2) cases diagnosed from 2000-2008 and all controls identified from 1990-2008, included those with imputed data, and (3) all women split into two follow-up periods, 1990-2000 and 2000-2008. In the third model, the proximate prolactin level for the first period was the 1990 value and the distant value was set to the median with a missing indicator, while the proximate level for the second period was the 2000 value and the distant level was the 1990 value. 2,013 cases and 3,031 controls were available; 733 cases were diagnosed after 2000 and 451 had measured prolactin for both bloods. The correlation between the 1990 and 2000 prolactin values was 0.35 (ICC=0.38). In the first model, there was a suggestion of an increased risk for proximate prolactin levels (RR, top vs. bottom quartile=1.44, 95%CI=0.93-2.23, p-trend=0.03), but not for the distant value (RR=0.75, 95%CI=0.50-1.14, p-trend=0.45). Similar results were observed in the second model (proximate RR=1.22, 95%CI=0.87-1.72, p-trend=0.12; distant RR=0.87, 95%CI=0.68-1.11, p-trend=0.93). The third model showed an increase risk for proximate levels (RR=1.53, 95%CI=1.28-1.83, p-trend&lt;0.001) and a suggestive positive association for the distant value (RR=1.27, 95%CI=0.95-1.69, p-trend=0.19). Further analyses will evaluate ER+ disease and interactions over time in prolactin levels. Our data suggest that proximate prolactin levels are more strongly associated with risk, and if prolactin were to be included in risk prediction models it may need to be measured at least every 10 years.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3730. doi:10.1158/1538-7445.AM2011-3730