In a provocative study, Lamont et al.1 reported a lower hospitalization rate for acute myocardial infarction during a 5-year follow-up of 5980 survivors of early-stage postmenopausal breast carcinoma, compared with 23,165 age-matched women without a history of breast carcinoma. The overall hazard ratio was 0.66 (95% confidence interval, 0.49–0.88).1 The authors proposed two potential explanations for their findings: 1) estrogens play a pathogenetic role in the development of breast carcinoma and may be protective against ischemic heart disease (IHD); and 2) tamoxifen, commonly used in the treatment of breast carcinoma, may afford cardiac protection, partly through reduction of insulin-like growth factor-1 (IGF-1).

Although we commend their study, we believe the authors' interpretations are not supported by recent data. Indeed, no cardioprotective effect of estrogens was observed in three large randomized studies comparing estrogen/progestagen or estrogen alone with placebo.2 Randomized trials with the selective estrogen receptor modulators, tamoxifen and raloxifen, have yielded mostly negative results with regards to cardioprotection.1 Finally, IGF-1, contrary to previous beliefs, is emerging as a robust cardioprotective factor, given its insulin-sensitizing, vasodilatatory, antiinflammatory, antioxidant, and vascular antiapoptotic actions.3 Further support for a vasculoprotective effect of IGF-1 was provided by recent studies, including > 1000 subjects, showing an inverse relation between circulating IGF-1 concentrations and carotid intimal-medial thickness,4 development of IHD or diabetes mellitus, and complications after myocardial infarction.3

IGF-1 has been implicated in the development of breast carcinoma and other types of malignancies in many experimental studies and in several prospective investigations.5 We propose increased IGF-1 bioavailability as an alternative mechanism underlying the decreased risk of myocardial infarction among survivors of breast carcinoma. Prolonged exposure to increased IGF-1 concentrations may simultaneously reduce cardiovascular risk while favoring carcinogenesis, the former by counteracting the harmful effects of cardiac risk factors and the latter via antiapoptotic and vasculogenetic activities.3, 4


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