See related article:
A population-based study
Article first published online: 6 JUL 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 23, pages 6012–6013, 1 December 2012
How to Cite
Lipscombe, L. L. and Rochon, P. A. (2012), Reply to association between tamoxifen treatment and diabetes . Cancer, 118: 6012–6013. doi: 10.1002/cncr.27516
See related article:
- Issue published online: 19 NOV 2012
- Article first published online: 6 JUL 2012
We thank Drs. Hejazi and Rastmanesh for their interest in our article. The purpose of our study was to determine whether there is an association between tamoxifen therapy and diabetes, and our findings will need to be confirmed in other populations. Although our population-based databases have the advantage of providing a large sample size with which to address that question, they lack detailed clinical information such as that regarding weight gain and other risk factors.
We agree that the mechanisms postulated for this association are uncertain. We acknowledge that tamoxifen is a selective estrogen receptor modulator, and that its effects on estrogen vary by tissue site. As we discuss in our article,1 there is evidence that estrogen protects against beta-cell failure and diabetes,2-4 leading to speculation that the observed increase in diabetes may be related to its estrogen inhibitory effects at the beta-cell level. This hypothesis is supported by the finding that tamoxifen induces beta-cell apoptosis and insulin deficiency in mice through direct estrogen antagonism.3 However, as the authors point out, alternative hypotheses such as the potential inflammatory effects of tamoxifen also need to be considered. Further studies that include more comprehensive clinical and metabolic data are needed to explore this intriguing finding.
Supported by Cancer Care Ontario and the Ontario Institute for Cancer Research (through funding provided by the Ministry of Health and Long-Term Care and the Ministry of Research and Innovation of the Government of Ontario) and a Canadian Diabetes Association/ Canadian Institutes for Health Research (CIHR) Clinician Scientist Award.
CONFLICT OF INTEREST DISCLOSURES
Dr. Lipscombe receives salary support from the Canadian Diabetes Association/CIHR Clinician Scientist Award.
- 1Association between tamoxifen treatment and diabetes: a population-based study [published online ahead of print September 20, 2011]. Cancer. doi: 10.1002/cncr.26559., , , et al.
- 2Heart and Estrogen/progestin Replacement Study. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003; 138: 1-9., , , et al;
- 3Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Proc Natl Acad Sci U S A. 2006; 103: 9232-9237., , , et al.
- 4Minireview: estrogenic protection of beta-cell failure in metabolic diseases. Endocrinology. 2010; 151: 859-864., .
Lorraine L. Lipscombe MD, MSc* , Paula A. Rochon MD, MPH* , * Women's College Research Institute, Women's College Hospital, Department of Medicine, University of Toronto; Institute for Clinical Evaluative Sciences, Department of Health Policy, Management and Evaluation, University of Toronto; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada