Hormonal determinants of mammographic density and density change

被引:27
作者
Gabrielson, Marike [1 ]
Azam, Shadi [1 ]
Hardell, Elina [1 ]
Holm, Madeleine [1 ]
Ubhayasekera, Kumari A. [2 ]
Eriksson, Mikael [1 ]
Backlund, Magnus [1 ]
Bergquist, Jonas [2 ]
Czene, Kamila [1 ]
Hall, Per [1 ,3 ]
机构
[1] Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, SE-17177 Stockholm, Sweden
[2] Uppsala Univ, Dept Chem BMC, Analyt Chem & Neurochem, Uppsala, Sweden
[3] South Gen Hosp, Dept Oncol, Stockholm, Sweden
基金
瑞典研究理事会;
关键词
Mammographic density; Mammographic density change; Plasma hormones; BREAST-CANCER RISK; ESTROGEN-PLUS-PROGESTIN; ENDOGENOUS SEX-HORMONES; POSTMENOPAUSAL WOMEN; BINDING GLOBULIN; AGE; ASSOCIATION; PROLACTIN; BIOMARKER; STEROIDS;
D O I
10.1186/s13058-020-01332-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm(2)) and annual MD change (cm(2)/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 cm(2)per doubling of hormone concentration), 17OH-progesterone (+ 1.09 cm(2)), oesterone sulphate (+ 1.42 cm(2)), prolactin (+ 2.11 cm(2)) and SHBG (+ 4.18 cm(2)), and inversely associated with 11-deoxycortisol (- 1.33 cm(2)). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was - 0.8 cm(2). Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was - 0.96 cm(2)and - 1.16 cm(2)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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页数:12
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