RANKL and OPG and their influence on breast volume changes during pregnancy in healthy women

Marius Wunderle,Josef M Penninger,Michael P Lux,Matthias W Beckmann,Christian M Bayer,Ruediger Schulz-Wendtland,Michael O Schneider,Eva Schwenke,Matthias Ruebner,Martin C Koch,Carolin C Hack,Ivona Kozieradzki,Sebastian M Jud,Lothar Häberle,Peter A Fasching,Judith Schwitulla

doi:10.1038/s41598-020-62070-3

Abstract

Breast cancer risk is reduced by number of pregnancies and breastfeeding duration, however studies of breast changes during or after pregnancy are rare. Breast volume changes – although not linked to breast cancer risk – might be an interesting phenotype in this context for correlative studies, as changes of breast volume vary between pregnant women. Serum receptor activator of nuclear factor kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG) were measured prospectively before gestational week 12, and three-dimensional breast volume assessments were performed. A linear regression model including breast volume at the start of pregnancy, RANKL, OPG, and other factors was used to predict breast volume at term. The mean breast volume was 413 mL at gestational week 12, increasing by a mean of 99 mL up to gestational week 40. In addition to body mass index and breast volume at the beginning of pregnancy, RANKL and OPG appeared to influence breast volume with a mean increase by 32 mL (P = 0.04) and a mean reduction by 27 mL (P = 0.04), respectively. Linking the RANKL/RANK/OPG pathway with breast volume changes supports further studies aiming at analysing breast changes during pregnancy with regard to breast cancer risk.

Highlights

Breast cancer risk is reduced by number of pregnancies and breastfeeding duration, studies of breast changes during or after pregnancy are rare
At gestational week 12, RANKL was detectable in the serum of 35 women (35%) and OPG was detectable in the serum of 38 women (38%)
RANKL serum values did not appear to have an influence on breast volumes at week 12 or week 40 (Fig. 2a,b), while women with detectable OPG in the serum appeared to have lower breast volumes than pregnant women who did not have detectable OPG at either point (Fig. 3a,b)

Summary

Introduction

Breast cancer risk is reduced by number of pregnancies and breastfeeding duration, studies of breast changes during or after pregnancy are rare. In addition to body mass index and breast volume at the beginning of pregnancy, RANKL and OPG appeared to influence breast volume with a mean increase by 32 mL (P = 0.04) and a mean reduction by 27 mL (P = 0.04), respectively. Mammographic density as a risk factor for breast cancer correlates inversely with the number of pregnancies, as has been shown in several cross-sectional and case–control studies[5,6,7,8,9,10,11]. Www.nature.com/scientificreports on average after pregnancy, there is a very variable response to pregnancy in each woman, with some women losing up to almost 50% of mammographic density after pregnancy, while others even have a 15% increase[12]

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