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Breast Cancer Research
Published in: Breast Cancer Research 1/2020

01-12-2020 | Breast Cancer | Research article

Hormonal determinants of mammographic density and density change

Authors: Marike Gabrielson, Shadi Azam, Elina Hardell, Madeleine Holm, Kumari A. Ubhayasekera, Mikael Eriksson, Magnus Bäcklund, Jonas Bergquist, Kamila Czene, Per Hall

Published in: Breast Cancer Research | Issue 1/2020

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Abstract

Background

Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm2) and annual MD change (cm2/year).

Methods

This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n = 3), androgen (n = 7), oestrogen (n = 2) and corticoid (n = 5) pathways were analysed by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS), as well as peptide hormones and proteins (n = 2). MD was measured as a dense area using the STRATUS method (mean over the left and right breasts) and mean annual MD change over time.

Results

Greater baseline mean MD was associated with overall higher concentrations of progesterone (average + 1.29 cm2 per doubling of hormone concentration), 17OH-progesterone (+ 1.09 cm2), oesterone sulphate (+ 1.42 cm2), prolactin (+ 2.11 cm2) and SHBG (+ 4.18 cm2), and inversely associated with 11-deoxycortisol (− 1.33 cm2). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was − 0.8 cm2. Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was − 0.96 cm2 and − 1.16 cm2 lesser, for women in the highest quartile concentrations of testosterone and free testosterone, respectively, compared to those with the lowest concentrations.

Conclusions

Our results suggest that, whereas hormones from the progestogen, oestrogen and corticoid pathways drive baseline MD, MD change over time is mainly driven by androgens. This study emphasises the complexity of risk factors for breast cancer and their mechanisms of action.
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Metadata
Title
Hormonal determinants of mammographic density and density change
Authors
Marike Gabrielson
Shadi Azam
Elina Hardell
Madeleine Holm
Kumari A. Ubhayasekera
Mikael Eriksson
Magnus Bäcklund
Jonas Bergquist
Kamila Czene
Per Hall
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-01332-4

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