Relationship of circulating insulin-like growth factor-I and binding proteins 1-7 with mammographic density among women undergoing image-guided diagnostic breast biopsy.
BACKGROUND
Mammographic density (MD) is a strong breast cancer risk factor that reflects fibroglandular and adipose tissue composition, but its biologic underpinnings are poorly understood. Insulin-like growth factor binding proteins (IGFBPs) are markers that may be associated with MD given their hypothesized role in breast carcinogenesis. IGFBPs sequester IGF-I, limiting its bioavailability. Prior studies have found positive associations between circulating IGF-I and the IGF-I:IGFBP-3 ratio and breast cancer risk. We evaluated the associations of IGF-I, IGFBP-3, and six other IGFBPs with MD.


METHODS
Serum IGF measures were quantified in 296 women, ages 40-65, undergoing diagnostic image-guided breast biopsy. Volumetric density measures (MD-V) were assessed in pre-biopsy digital mammograms using single X-ray absorptiometry. Area density measures (MD-A) were estimated by computer-assisted thresholding software. Age, body mass index (BMI), and BMI2-adjusted linear regression models were used to examine associations of serum IGF measures with MD. Effect modification by BMI was also assessed.


RESULTS
IGF-I and IGFBP-3 were not strongly associated with MD after BMI adjustment. In multivariable analyses among premenopausal women, IGFBP-2 was positively associated with both percent MD-V (β = 1.49, p value = 0.02) and MD-A (β = 1.55, p value = 0.05). Among postmenopausal women, positive relationships between IGFBP-2 and percent MD-V (β = 2.04, p = 0.003) were observed; the positive associations between IGFBP-2 and percent MD-V were stronger among lean women (BMI < 25 kg/m2) (β = 5.32, p = 0.0002; p interaction = 0.0003).


CONCLUSIONS
In this comprehensive study of IGFBPs and MD, we observed a novel positive association between IGFBP-2 and MD, particularly among women with lower BMI. In concert with in vitro studies suggesting a dual role of IGFBP-2 on breast tissue, promoting cell proliferation as well as inhibiting tumorigenesis, our findings suggest that further studies assessing the role of IGFBP-2 in breast tissue composition, in addition to IGF-1 and IGFBP-3, are warranted.
['Hada|Manila|M|0000-0002-6960-5871', 'Oh|Hannah|H|', 'Pfeiffer|Ruth M|RM|', 'Falk|Roni T|RT|', 'Fan|Shaoqi|S|', 'Mullooly|Maeve|M|', 'Pollak|Michael|M|', 'Geller|Berta|B|', 'Vacek|Pamela M|PM|', 'Weaver|Donald|D|', 'Shepherd|John|J|', 'Wang|Jeff|J|', 'Fan|Bo|B|', 'Mahmoudzadeh|Amir Pasha|AP|', 'Malkov|Serghei|S|', 'Herschorn|Sally|S|', 'Brinton|Louise A|LA|', 'Sherman|Mark E|ME|', 'Gierach|Gretchen L|GL|']
D000328:Adult D015415:Biomarkers D000071060:Breast Density D001943:Breast Neoplasms D003430:Cross-Sectional Studies D005260:Female D006801:Humans D061705:Image-Guided Biopsy D018969:Insulin-Like Growth Factor Binding Proteins D007334:Insulin-Like Growth Factor I D008327:Mammography D008875:Middle Aged D012307:Risk Factors
Mammographic density Insulin-like growth factor Insulin-like growth factor binding proteins Breast density Breast neoplasm