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Breast Cancer Res. 2019 Jul 23;21(1):81. doi: 10.1186/s13058-019-1162-8.

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

Author information

1
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. manila.hada@nih.gov.
2
Division of Health Policy and Management, College of Health Sciences, Korea University, Seoul, Republic of Korea.
3
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
4
Royal College of Surgeons in Ireland, Dublin, Ireland.
5
McGill University, Montreal, QC, Canada.
6
University of Vermont and Vermont Cancer Center, Burlington, VT, USA.
7
University of Hawaii, Honolulu, Hawaii, USA.
8
Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
9
University of California San Francisco, San Francisco, CA, USA.
10
Mayo Clinic, Jacksonville, FL, USA.

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.

KEYWORDS:

Breast density; Breast neoplasm; Insulin-like growth factor; Insulin-like growth factor binding proteins; Mammographic density

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