Hormonal determinants of mammographic density and density change
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RESEARCH ARTICLE
Open Access
Hormonal determinants of mammographic density and density change Marike Gabrielson1* , Shadi Azam1, Elina Hardell1, Madeleine Holm1, Kumari A. Ubhayasekera2, Mikael Eriksson1, Magnus Bäcklund1, Jonas Bergquist2, Kamila Czene1 and Per Hall1,3
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. Keywords: Mammographic density, Mammographic density change, Plasma hormones
Introduction Breast cancer is the most commonly diagnosed cancer in women around the world, and mammographic breast density (MD) is one of the strongest risk factors. MD reflects the radiographically dense fibroglandular tissue, which appears bright on the mammogram. Women with high breast density have a 4–6-fold increased breast cancer risk as * Correspondence: [email protected] 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, SE-171 77 Stockholm, Sweden Full list of author information is available at the end of the article
compared to women with low density [1–4]. Studies analysing the relation between MD and endogenous plasma hormones have shown inconsistent results [5–13]; it remains largely uncertain how progestogens, oestrogens, androgens and corticoids are associated with MD in the normal, nonmalignant breast. MD is a highly inheritable trait, but it is also influenced by we
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