Breast Cancer Research and Treatment

, Volume 128, Issue 1, pp 243–250 | Cite as

Expression of IGF1R in normal breast tissue and subsequent risk of breast cancer

  • Rulla M. Tamimi
  • Graham A. Colditz
  • Yihong Wang
  • Laura C. Collins
  • Rong Hu
  • Bernard Rosner
  • Hanna Y. Irie
  • James L. Connolly
  • Stuart J. Schnitt
Epidemiology

Abstract

The growth hormone and insulin-like growth factor (IGF) axis plays an essential role in the growth and development of the mammary gland. IGF1 and IGF1 receptor (IGF1R) may also play a role in the early transformation of mammary cells. Using a nested case–control design, the association between IGF1R expression in normal breast tissue from benign biopsies and subsequent risk of breast cancer was examined in patients enrolled in the Nurses’ Health Study. The tissue microarrays (TMAs) containing normal terminal duct lobular units (TDLUs) from benign breast biopsies were constructed. Immunostains for IGF1R were performed on sections cut from the TMAs. A total of 312 women had evaluable IGF1R staining in normal TDLUs; 75 subsequently developed breast cancer (cases) and 237 did not (controls). The epithelial cells in the normal TDLUs were scored for both cytoplasmic and membrane staining for IGF1R. Cytoplasmic IGF1R expression was positively associated with subsequent risk of breast cancer (OR = 2.47, 95% CI 1.41–4.33). Women having TDLU epithelial cells showed little or no membrane expression of IGF1R, but those with high levels of cytoplasmic IGF1R were at the highest breast cancer risk and were 15 times more likely to develop subsequent breast cancer when compared with women who had little or no membrane or cytoplasmic IGF1R expression in their TDLU epithelial cells (OR = 15.9, 95% CI 3.6–69.8). In this study, it was demonstrated that IGF1R expression patterns in epithelial cells of normal TDLUs in benign breast biopsies were associated with an increased risk of subsequent breast cancer. Further studies to confirm these findings are necessary.

Keywords

IGF1R Normal TDLU Benign breast disease Tissue microarrays 

Abbreviations

ADH

Atypical ductal hyperplasia

ALH

Atypical lobular hyperplasia

BBD

Benign breast disease

BMI

Body mass index

CI

Confidence interval

ER

Estrogen receptor

H&E

Hematoxylin and eosin

IGF

Insulin-like growth factor

IGF1R

Insulin-like growth factor receptor

IRS1

Insulin receptor substrate 1

NHS

Nurses’ Health Study.

OR

Odds Ratio

PI3K

Phosphatidyl inositol-3 kinase

PR

Progesterone receptor

TDLUs

Normal terminal ductal lobular units

TMAs

Tissue microarrays

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Rulla M. Tamimi
    • 1
    • 2
  • Graham A. Colditz
    • 2
    • 3
  • Yihong Wang
    • 4
  • Laura C. Collins
    • 5
  • Rong Hu
    • 1
  • Bernard Rosner
    • 1
  • Hanna Y. Irie
    • 6
  • James L. Connolly
    • 5
  • Stuart J. Schnitt
    • 5
  1. 1.Channing Laboratory, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  3. 3.Department of SurgeryWashington University School of MedicineSt. LouisUSA
  4. 4.Department of Pathology, Montefiore Medical CenterAlbert Einstein Medical SchoolNew YorkUSA
  5. 5.Department of PathologyBeth Israel Deaconess Medical Center and Harvard Medical SchoolBostonUSA
  6. 6.Department of Cell BiologyHarvard Medical SchoolBostonUSA

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