March 2012, 14:R44,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 13 Mar 2012
Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and lobule type in the Nurses' Health Study II
Previous research in the Nurses' Health Study (NHS) and the NHSII observed that, among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules (a marker of complete involution) versus other lobule types were at lower risk of subsequent breast cancer. Studies in animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit involution of lobules in the breast; however, this has not been studied in humans.
We conducted a cross-sectional study among 472 women in the NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and 2002 and provided blood samples between 1996 and 1999. A pathologist, blinded to exposure status, classified lobule type in normal adjacent tissue on available biopsy slides according to the number of acini per lobule. For each participant, the pathologist determined the predominant lobule type (that is, type 1, type 2, or type 3) and whether any type 1 or any type 3 lobules were present. Lobule type was then classified as: predominant type 1/no type 3 lobules, which is suggestive of complete involution; or other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and the ratio of IGF-1:IGFBP-3 levels with lobule type.
In univariate analyses, greater age, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type 1/no type 3 lobules (P < 0.05). In multivariate models adjusting for age and assay batch, higher IGF-1 levels were associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.37, 95% confidence interval = 0.15 to 0.89). Greater ratios of IGF-1:IGFBP-3 levels were also associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.26, 95% confidence interval = 0.11 to 0.64). These results were slightly attenuated after adjustment for other potential predictors of lobule type.
Higher IGF-1 levels and a greater IGF-1:IGFBP-3 ratio were associated with decreased odds of having predominant type 1 lobules/no type 3 lobules among women with proliferative BBD in the NHSII. This study provides further evidence for the role of insulin-like growth factors in the structure of breast lobules and lobular involution.
Russo J, Russo IH: Toward a physiological approach to breast cancer prevention. Cancer Epidemiol Biomarkers Prev 1994, 3:353–364.PubMed
McKian KP, Reynolds CA, Visscher DW, Nassar A, Radisky DC, Vierkant RA, Degnim AC, Boughey JC, Ghosh K, Anderson SS, Minot D, Caudill JL, Vachon CM, Frost MH, Pankratz VS, Hartmann LC: Novel breast tissue feature strongly associated with risk of breast cancer. J Clin Oncol 2009, 27:5893–5898.PubMedCrossRef
Key TJ, Appleby PN, Reeves GK, Roddam AW: Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 11:530–542.
Byrne C, Colditz GA, Willett WC, Speizer FE, Pollak M, Hankinson SE: Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density. Cancer Res 2000, 60:3744–3748.PubMed
Su X, Colditz GA, Willett WC, Collins LC, Schnitt SJ, Connolly JL, Pollak MN, Rosner B, Tamimi RM: Genetic variation and circulating levels of IGF-I and IGFBP-3 in relation to risk of proliferative benign breast disease. Int J Cancer 126:180–190.
Rosner B: Percentage points for a generalized ESD many-outlier procedure. Technometrics 1983, 25:165–172.
Boyd NF, Lockwood GA, Martin LJ, Byng JW, Yaffe MJ, Tritchler DL: Mammographic density as a marker of susceptibility to breast cancer: a hypothesis. IARC Sci Publ 2001, 154:163–169.PubMed
Ghosh K, Hartmann LC, Reynolds C, Visscher DW, Brandt KR, Vierkant RA, Scott CG, Radisky DC, Sellers TA, Pankratz VS, Vachon CM: Association between mammographic density and age-related lobular involution of the breast. J Clin Oncol 28:2207–2212.
- Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and lobule type in the Nurses' Health Study II
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Breast Cancer Research
- Online Date
- March 2012
- Online ISSN
- BioMed Central
- Additional Links
- Author Affiliations
- 1. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Ave 3rd Floor, Boston, MA, 02115, USA
- 2. Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA
- 3. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, 02115, USA
- 4. McGill University, Jewish General Hospital, 3755 Cote St. Catherine Rd, Montreal, Quebec, H3T 1E2, Canada