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Breast Cancer Research
Published in: Breast Cancer Research 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

Relationship of circulating insulin-like growth factor-I and binding proteins 1–7 with mammographic density among women undergoing image-guided diagnostic breast biopsy

Authors: Manila Hada, Hannah Oh, Ruth M. Pfeiffer, Roni T. Falk, Shaoqi Fan, Maeve Mullooly, Michael Pollak, Berta Geller, Pamela M. Vacek, Donald Weaver, John Shepherd, Jeff Wang, Bo Fan, Amir Pasha Mahmoudzadeh, Serghei Malkov, Sally Herschorn, Louise A. Brinton, Mark E. Sherman, Gretchen L. Gierach

Published in: Breast Cancer Research | Issue 1/2019

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Abstract

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.
Appendix
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Metadata
Title
Relationship of circulating insulin-like growth factor-I and binding proteins 1–7 with mammographic density among women undergoing image-guided diagnostic breast biopsy
Authors
Manila Hada
Hannah Oh
Ruth M. Pfeiffer
Roni T. Falk
Shaoqi Fan
Maeve Mullooly
Michael Pollak
Berta Geller
Pamela M. Vacek
Donald Weaver
John Shepherd
Jeff Wang
Bo Fan
Amir Pasha Mahmoudzadeh
Serghei Malkov
Sally Herschorn
Louise A. Brinton
Mark E. Sherman
Gretchen L. Gierach
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2019
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-019-1162-8

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