No relationship between circulating levels of sex steroids and mammographic breast density: the Prospect-EPIC cohort.
BACKGROUND
High breast density is associated with increased breast cancer risk. Epidemiologic studies have shown an increase in breast cancer risk in postmenopausal women with high levels of sex steroids. Hence, sex steroids may increase postmenopausal breast cancer risk via an increase of breast density. The objective of the present study was to study the relation between circulating oestrogens and androgens as well as sex hormone binding globulin (SHBG) in relation to breast density.


METHODS
We conducted a cross-sectional study among 775 postmenopausal women, using baseline data of a random sample of the Prospect-EPIC study. Prospect-EPIC is one of two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition, and women were recruited via a breast cancer screening programme. At enrolment a nonfasting blood sample was taken and a mammogram was made. Oestrone, oestradiol, dehydroepiandrosterone sulfate, androstenedione, testosterone and SHBG levels were measured, using double-antibody radioimmunoassays. Concentrations of free oestradiol and free testosterone were calculated from the measured oestradiol, testosterone and SHBG levels Mammographic dense and nondense areas were measured using a semiquantitative computerized method and the percentage breast density was calculated. Mean breast measures for quintiles of hormone or SHBG levels were estimated using linear regression analyses.


RESULTS
Both oestrogens and testosterone were inversely related with percent breast density, but these relationships disappeared after adjustment for BMI. None of the sex steroids or SHBG was associated with the absolute measure of breast density, the dense area.


CONCLUSIONS
The results of our study do not support the hypothesis that sex steroids increase postmenopausal breast cancer risk via an increase in breast density.
Verheus
Martijn
M
Julius Center for Health Sciences and Primary Care, Room Str 6,131, PO Box 85500, University Medical Center Utrecht, Utrecht 3508 GA, The Netherlands.
Peeters
Petra H M
PH
van Noord
Paulus A H
PA
van der Schouw
Yvonne T
YT
Grobbee
Diederick E
DE
van Gils
Carla H
CH
D000328:Adult; D000728:Androgens / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*
D000728:Androgens; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone
J Natl Cancer Inst. 2004 Apr 21;96(8):621-8
15100340
J Steroid Biochem Mol Biol. 2003 Sep;86(3-5):225-30
14623515
J Natl Cancer Inst. 1988 Jul 20;80(10):772-4
3385783
Epidemiology. 1992 Nov;3(6):523-6
1420519
Eur J Cancer Prev. 1996 Oct;5(5):319-27
8972250
Int J Epidemiol. 1997;26 Suppl 1:S6-14
9126529
Int J Epidemiol. 1997;26 Suppl 1:S37-48
9126532
Int J Epidemiol. 1997;26 Suppl 1:S49-58
9126533
Lancet. 1997 Oct 11;350(9084):1047-59
10213546
J Clin Endocrinol Metab. 1999 Oct;84(10):3666-72
10523012
Phys Med Biol. 1994 Oct;39(10):1629-38
15551535
J Clin Endocrinol Metab. 2005 Mar;90(3):1414-9
15572431
Cancer Epidemiol Biomarkers Prev. 2005 Jun;14(6):1411-7
15941949
J Natl Cancer Inst. 2005 Sep 21;97(18):1366-76
16174858
Lancet Oncol. 2005 Oct;6(10):798-808
16198986
Am J Epidemiol. 2005 Nov 1;162(9):826-34
16177147
Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11 Pt 1):2634-40
16284389
Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11 Pt 1):2641-7
16284390
Endocr Relat Cancer. 2005 Dec;12(4):1071-82
16322344
Menopause. 2005 Nov-Dec;12(6):668-78
16278609
Breast. 2006 Feb;15(1):20-8
16000251
Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):961-6
16702377
Cancer Epidemiol Biomarkers Prev. 2006 Jun;15(6):1159-69
16775176
Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1502-8
16896040
J Clin Oncol. 2007 Apr 10;25(11):1323-8
17312333
Cancer Epidemiol Biomarkers Prev. 2000 Sep;9(9):911-5
11008908
J Natl Cancer Inst. 2002 Apr 17;94(8):606-16
11959894
Breast Cancer Res Treat. 2002 Mar;72(2):107-15
12038701
JAMA. 2002 Jul 17;288(3):321-33
12117397
Br J Cancer. 2002 Oct 7;87(8):876-82
12373602
Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1065-71
12376508
Eur J Epidemiol. 2001;17(11):1047-53
12380720
J Natl Cancer Inst. 2003 Jan 1;95(1):30-7
12509398
Public Health Nutr. 2002 Dec;5(6B):1113-24
12639222
JAMA. 2003 Jun 25;289(24):3243-53
12824205
J Natl Cancer Inst. 1986 Sep;77(3):617-20
3462405