title: The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomized breast cancer chemoprevention trial.
abstract: BACKGROUND
  We have previously reported the favourable effect of transdermal estradiol (E2), relative to oral conjugated equine oestrogen (CEE), on ultrasensitive C-reactive protein after 12 months of treatment in a retinoid-placebo controlled two-by-two randomized breast cancer prevention trial (Decensi A et al (2002) Circulation106 10 1224-8). Here, we investigate the changes in lipids and clotting profile in patients of the same trial.
  
  
  RESULTS
  Recent post-menopausal women were randomised to either oral CEE 0.625 mg/day and placebo (n = 55), CEE and fenretinide 200 mg/day (n = 56), transdermal E2 50 mg/day and placebo (n = 59) or E2 and fenretinide 200 mg/day (n = 56). Sequential medroxyprogesterone acetate 10 mg/day was given in each group. After 12 months, there was a statistically significant effect of the route of administration of hormone replacement therapy (HRT) on fibrinogen levels; the median percentage change being -5.7% with CEE and -1.1% with E2 (p = 0.012). Total cholesterol decreased in all arms (p < 0.0001). HDL-C decreased significantly with transdermal E2 (p = 0.006) compared to oral CEE and with fenretinide relative to placebo (p<0.001). Triglycerides exhibited an opposite modulation in the HRT route, with a 21.4% median increase with oral CEE and an 8.6% reduction with transdermal E2 (p < 0.0001). Antithrombin-III showed a 4% borderline significant reduction in the fenretinide arm relative to placebo, irrespective of the HRT administration route (p = 0.055).
  
  
  CONCLUSIONS
  Our data indicate that transdermal E2 may be preferable to oral CEE based on its safer cardiovascular risk profile. Fenretinide modified some cardiovascular risk biomarkers and confirmed a safer profile compared to other retinoids.
authors.affiliation: Cancer Prevention and Genetics, European Institute of Oncology, 20141 Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lazzeroni
authors.forename: D
authors.initials: D
authors.lastname: Macis
authors.forename: A
authors.initials: A
authors.lastname: Decensi
authors.forename: S
authors.initials: S
authors.lastname: Gandini
authors.forename: M T
authors.initials: MT
authors.lastname: Sandri
authors.forename: D
authors.initials: D
authors.lastname: Serrano
authors.forename: A
authors.initials: A
authors.lastname: Guerrieri-Gonzaga
authors.forename: H
authors.initials: H
authors.lastname: Johansson
authors.forename: S
authors.initials: S
authors.lastname: Mora
authors.forename: C
authors.initials: C
authors.lastname: Daldoss
authors.forename: U
authors.initials: U
authors.lastname: Omodei
authors.forename: B
authors.initials: B
authors.lastname: Bonanni