Abstract
BackgroundBreast density, the amount of fibroglandular tissue in the adult breast for a women’s age and body mass index, is a strong biomarker of susceptibility to breast cancer, which may, like breast cancer risk itself, be influenced by events early in life. In the present study, we investigated the association between pre-natal exposures and breast tissue composition.MethodsA sample of 500 young, nulliparous women (aged approximately 21 years) from a U.K. pre-birth cohort underwent a magnetic resonance imaging examination of their breasts to estimate percent water, a measure of the relative amount of fibroglandular tissue equivalent to mammographic percent density. Information on pre-natal exposures was collected throughout the mothers’ pregnancy and shortly after delivery. Regression models were used to investigate associations between percent water and pre-natal exposures. Mediation analysis, and a systematic review and meta-analysis of the published literature, were also conducted.ResultsAdjusted percent water in young women was positively associated with maternal height (p for linear trend [p t] = 0.005), maternal mammographic density in middle age (p t = 0.018) and the participant’s birth size (p t < 0.001 for birthweight). A 1-SD increment in weight (473 g), length (2.3 cm), head circumference (1.2 cm) and Ponderal Index (4.1 g/cm3) at birth were associated with 3 % (95 % CI 2–5 %), 2 % (95 % CI 0–3 %), 3 % (95 % CI 1–4 %) and 1 % (95 % CI 0–3 %), respectively, increases in mean adjusted percent water. The effect of maternal height on the participants’ percent water was partly mediated through birth size, but there was little evidence that the effect of birthweight was primarily mediated via adult body size. The meta-analysis supported the study findings, with breast density being positively associated with birth size.ConclusionsThese findings provide strong evidence of pre-natal influences on breast tissue composition. The positive association between birth size and relative amount of fibroglandular tissue indicates that breast density and breast cancer risk may share a common pre-natal origin.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0751-z) contains supplementary material, which is available to authorized users.
Highlights
Breast density, the amount of fibroglandular tissue in the adult breast for a women’s age and body mass index, is a strong biomarker of susceptibility to breast cancer, which may, like breast cancer risk itself, be influenced by events early in life
We investigated the relationship between prospectively collected data on a wide range of pre-natal exposures, including birth size, and breast tissue composition, as assessed by ionising radiation-free magnetic resonance imaging (MRI), in nulliparous young women within a British pre-birth cohort, and we conducted a systematic review of the relevant published literature
Young, nulliparous women born from singleton pregnancies who regularly participated in follow-up surveys and had never been diagnosed with cancer or a hormone-related disease were invited to attend an MRI examination of their breasts at the University of Bristol Clinical Research and Imaging Centre between June 2011 and November 2014
Summary
The amount of fibroglandular tissue in the adult breast for a women’s age and body mass index, is a strong biomarker of susceptibility to breast cancer, which may, like breast cancer risk itself, be influenced by events early in life. The mechanisms linking birth size to risk are not known, but birth size may be a correlate of in utero exposures to mitogens [1] Such mitogens may influence the size of the stem cell pool in the embryonic breast, which, in turn, affects the development of the gland at puberty and, breast cancer risk later in life [3]. If true, such a hypothesis would suggest that the association between pre-natal exposures and breast cancer risk may be mediated, at least in part, by influences on breast tissue composition in early adulthood. There has been no investigation of the role of pre-natal exposures in young women (i.e., prior to the breast tissue being affected by reproductive-related events)
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