The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant
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To the Editor,
Increased steroid hormone levels have been associated with breast cancer risk and they can be affected by the intake of exogenous hormones, in particular during postmenopausal hormone replacement therapy (HRT) . The role of estrogens and progestins in HRT varies. In the placebo controlled WHI study, long-term estrogen plus progestin treatment evolved as a breast cancer risk factor [2, 3, 4], but estrogen treatment alone showed a lower rate of breast cancer . The latter is consistent with laboratory results showing a protective mechanism through estrogen induced apoptosis [6, 7]. The effect of progestins on breast cancer is controversial, biological studies observed proliferative as well as antimitogenic activity of these components [8, 9]. Variations in drug kinetics and dynamics could potentially contribute to the carcinogenic effect and therefore, the HRT-associated breast cancer risk can be addressed from the angle of drug metabolism and its known...
KeywordsBreast Cancer Risk Hormone Replacement Therapy Breast Cancer Case European Descent Breast Cancer Risk Factor
This study and the GENICA study was supported by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Institute of Pathology, Medical Faculty of the University of Bonn, Deutsches Krebsforschungszentrum, Heidelberg, and the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany. The SASBAC study was supported by the Märit and Hans Rausing’s Initiative Against Breast Cancer, the National Institutes of Health (RO1 CA58427), the Agency for Science, Technology and Research (A*STAR; Singapore), and the Swedish Research Council. J Li was a recipient of the A*STAR Graduate Scholarship. KH was supported by the Swedish Research Council (523-2006-972). MSC is a Senior Research Fellow of the Australian National Health and Medical Research Council and a Victorian Breast Cancer Research Consortium Group Leader. MCCS is supported by Cancer Council Victoria and by NHMRC (Grants 209057, 251533, 396414, 504711, 504715). The BBCC study was supported by the ELAN program of the University Hospital Erlangen. All authors disclose any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations.
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