TY - JOUR
T1 - Relationship of circulating insulin-like growth factor-I and binding proteins 1-7 with mammographic density among women undergoing image-guided diagnostic breast biopsy
AU - Hada, Manila
AU - Oh, Hannah
AU - Pfeiffer, Ruth M.
AU - Falk, Roni T.
AU - Fan, Shaoqi
AU - Mullooly, Maeve
AU - Pollak, Michael
AU - Geller, Berta
AU - Vacek, Pamela M.
AU - Weaver, Donald
AU - Shepherd, John
AU - Wang, Jeff
AU - Fan, Bo
AU - Mahmoudzadeh, Amir Pasha
AU - Malkov, Serghei
AU - Herschorn, Sally
AU - Brinton, Louise A.
AU - Sherman, Mark E.
AU - Gierach, Gretchen L.
N1 - Funding Information:
This project was supported in part by the Intramural Research Program of the US National Cancer Institute and a competitive award generated through proceeds from the sale of US breast cancer research postage stamps.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/7/23
Y1 - 2019/7/23
N2 - 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.
AB - 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.
KW - Breast density
KW - Breast neoplasm
KW - Insulin-like growth factor
KW - Insulin-like growth factor binding proteins
KW - Mammographic density
UR - http://www.scopus.com/inward/record.url?scp=85069764274&partnerID=8YFLogxK
U2 - 10.1186/s13058-019-1162-8
DO - 10.1186/s13058-019-1162-8
M3 - Article
C2 - 31337427
AN - SCOPUS:85069764274
SN - 1465-5411
VL - 21
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 81
ER -
