Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women.
BACKGROUND
Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates.


METHODS
In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method.


RESULTS
Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m(2) (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI.


CONCLUSIONS
These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels.
McCormack
Valerie A
VA
Cancer Research UK Epidemiology and Genetics Group, Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK. mccormackv@fellows.iarc.fr
Dowsett
Mitch
M
Folkerd
Elizabeth
E
Johnson
Nichola
N
Palles
Claire
C
Coupland
Ben
B
Holly
Jeff M
JM
Vinnicombe
Sarah J
SJ
Perry
Nicholas M
NM
dos Santos Silva
Isabel
I
D000368:Aged; D044383:Black People; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000208:ethnology* / Q000378:metabolism*; D017691:Caribbean Region; D003430:Cross-Sectional Studies; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008327:Mammography / Q000379:methods*; D008875:Middle Aged; D017698:Postmenopause; D013002:Somatomedins / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D006113:United Kingdom; D044465:White People
D004967:Estrogens; D006728:Hormones; D013002:Somatomedins; D013256:Steroids