Purpose: Higher circulating prolactin levels have been associated with higher mammographic density among postmenopausal women in some, but not all studies. However, few studies have examined the association between circulating levels of prolactin with dense area and non-dense area of the breast. Further, no study to date has examined the association between prolactin Nb2 lymphoma cell bioassay levels and mammographic density. The Nb2 lymphoma cell bioassay is a sensitive measure of somatolactogenic activity of prolactin in plasma and may be a more biologically relevant measure of prolactin compared to the immunoassay.

Methods: We conducted a cross-sectional study among postmenopausal women who were controls in the breast cancer case-control study nested in the Nurses' Health Study (NHS). Participants provided blood samples in 1989-1990 and mammograms were obtained from around the time of blood draw. Prolactin immunoassay levels were available for 835 postmenopausal women. Plasma samples from 220 of these women were also assayed for prolactin levels using the Nb2 lymphoma cell bioassay. Generalized linear models were used to assess the associations between plasma prolactin levels, as measured by an immunoassay or the bioassay, with percent mammographic density, total dense area, and total non-dense area. Models were adjusted for potential confounders including age, body mass index, parity, and breastfeeding, among others.

Results: Among the 835 postmenopausal women, those with prolactin immunoassay levels in the highest versus lowest quartile had significantly higher percent mammographic density (difference in percent density between quartile 4 and 1 = 3.5, p for trend=0.04) as well as lower non-dense area on mammogram (p-trend=0.01). Among the 220 postmenopausal women with both immunoassay and bioassay levels, there was no association between prolactin immunoassay levels and percent density (comparable difference=2.1, p-trend=0.78). However, among these same 220 women, higher prolactin levels as measured by the Nb2 lymphoma cell bioassay were strongly associated with higher percent density as well as with lower non-dense area (p for trend=<0.0001 and <0.0001 respectively).

Conclusion: Prolactin bioassay levels were positively associated with percent mammographic density and inversely associated with non-dense area among a sample of postmenopausal women. In these same women, we did not observe a statistically significant association with prolactin immunoassay levels, supporting the hypothesis that the Nb2 lymphoma cell bioassay may better reflect the biologically relevant portion of circulating prolactin. Future work should examine the relationship between Nb2 lymphoma cell bioassay prolactin levels and breast cancer risk.

Citation Format: Megan Rice, Shelley Tworoger, Susan Hankinson, Bernard Rosner, Charles Clevenger, Rulla Tamimi. Circulating prolactin levels and mammographic density in the Nurses' Health Studies. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 75.