title: HRT opposed to low-dose tamoxifen (HOT study): rationale and design.
abstract: The rationale for the HOT study is mainly based on the findings of the Italian Tamoxifen Prevention Study, where 5,408 healthy hysterectomized women aged 35-70 years were randomized to 20 mg/day of tamoxifen or placebo for 5 years. After 81.2 months median follow-up, 79 breast cancers occurred (34 on tamoxifen versus 45 on placebo, p=0.215). In the subgroup of 1,580 women who used estrogen replacement therapy (ERT) at some point during the study, 23 breast cancers were observed: 17 on placebo and 6 on tamoxifen (hazard ratio=0.35, 95% CI, 0.14-0.89). Pharmacokinetic and pharmacodynamic (surrogate endpoint biomarkers) studies showed that a lower dose of tamoxifen (such as 5 mg/day) does not affect the drug's activity on several biomarkers of both cardiovascular and breast cancer risk. We therefore propose a multicenter placebo-controlled phase III trial in postmenopausal healthy women on hormone replacement therapy (HRT) to assess whether the combination of HRT and low-dose tamoxifen retains the benefits while reducing the risks of either.
authors.affiliation: European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Decensi
authors.forename: Arianna
authors.initials: A
authors.lastname: Galli
authors.forename: Umberto
authors.initials: U
authors.lastname: Veronesi
mesh_terms: D001943:Breast Neoplasms / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D017698:Postmenopause; D012107:Research Design; D012307:Risk Factors; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen