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

  • Epidemiology
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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.

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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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Acknowledgments

The authors thank all the participants in the NHS for their outstanding dedication and commitment to this study. This study was supported by the Public Health Service Grants Nos. CA087969, CA046475, and SPORE in Breast Cancer CA089393, from the National Cancer Institute, the National Institutes of Health, Department of Health and Human Services and the Breast Cancer Research Foundation, and the American Cancer Society (to G. A. Colditz).

Competing Interests

None.

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Authors and Affiliations

  1. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA

    Rulla M. Tamimi, Rong Hu & Bernard Rosner

  2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA

    Rulla M. Tamimi & Graham A. Colditz

  3. Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Graham A. Colditz

  4. Department of Pathology, Montefiore Medical Center, Albert Einstein Medical School, New York, New York, USA

    Yihong Wang

  5. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA

    Laura C. Collins, James L. Connolly & Stuart J. Schnitt

  6. Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA

    Hanna Y. Irie

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  1. Rulla M. Tamimi
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Correspondence to Rulla M. Tamimi.

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Tamimi, R.M., Colditz, G.A., Wang, Y. et al. Expression of IGF1R in normal breast tissue and subsequent risk of breast cancer. Breast Cancer Res Treat 128, 243–250 (2011). https://doi.org/10.1007/s10549-010-1313-1

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  • DOI: https://doi.org/10.1007/s10549-010-1313-1

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