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Association between Insulin-Like Growth Factor (IGF-I) and Bone Mineral Density: Further Evidence Linking IGF-I to Breast Cancer Risk—Authors’ Response

Maine Center for Osteoporosis Research and Education St. Joseph Hospital Bangor, Maine 04401

Douglas P. Kiel

Hebrew Rehabilitation Center for Aged, Research and Training Institute, and Harvard Medical School Division on Aging Boston, Massachussetts

Jean A. Langlois

National Center for Injury Prevention and Control Atlanta, Georgia

Marjolein Visser

EMGO Institute Amsterdam, The Netherlands

We thank Dr. Yu for his thoughtful letter (above) summarizing the evidence for the associations among insulin-like growth factor-I, bone mineral density (BMD), and risk of breast cancer. In addition to the research mentioned above, data from the Framingham Heart Study also showed a strong positive association between BMD and risk of breast cancer (1). Although the findings to date are provocative, there are many unanswered questions. First, it has not yet been established that IGF-I levels are causally linked to breast cancer risk. Clearly, IGF-I is a growth factor that can promote mammary cell mitogenesis, but the precise relationship of this circulating peptide to local tumor development is not clear (2). Second, total serum levels of IGF-I may NOT reflect tissue bioactivity and therefore may be at best only a surrogate predictor of IGF-I activity at the cellular level. In particular tumor cells, there are several autocrine and paracrine networks that include IGF-I, IGF binding proteins (IGFBPs), and IGFBP-specific proteases. All or some of these proteins can promote neoplastic growth, but their activity cannot be discerned through measurement of circulating concentrations (2). Third, little is known about the status of the IGF type I receptor in relation to lifetime high or low IGF-I exposure at the tissue level (2). In sum, IGF-I is only one component of a complex and redundant network that almost certainly affects the pattern and activity of various tumors. Whether total serum levels of IGF-I provide an integrated assessment of this activity remains to be determined. We do agree that further research to delineate the relationships among IGF-I, BMD, and breast cancer risk is needed to determine the safety of growth hormone replacement therapy.

Footnotes

Address correspondence to: Clifford J. Rosen, M.D., Maine Center for Osteoporosis Research and Education, St. Joseph Hospital, 360 Broadway, Bangor, Maine 04401.

Received January 22, 1999.

References

1. Zhang Y, Kiel DP, Kreger BE, et al. 1997 Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med. 336:611–617.[Abstract/Free Full Text]
2. Rosen CJ, Pollak M. 1999 Circulating IGF-I: New perspectives for a new century. Trends Endocrinol Metab. In press.

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