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. 2008:2:67.
doi: 10.3332/ecancer.2008.67. Epub 2008 Feb 6.

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

M Lazzeroni  1 , D Macis, A Decensi, S Gandini, M T Sandri, D Serrano, A Guerrieri-Gonzaga, H Johansson, S Mora, C Daldoss, U Omodei, B Bonanni
Affiliations

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

M Lazzeroni et al. Ecancermedicalscience. 2008.

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.

Methods and 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.

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Figures

Figure 1:
Figure 1:
Effect of HRT on plasma fibrinogen concentration at baseline and after 12 months of treatment (p = 0.012)
Figure 2:
Figure 2:
Different modulation of HDL-C in the four arms of treatment (CEE versus E2: p < 0.006, without 4-HPR versus with 4-HPR: p < 0.001)
Figure 3:
Figure 3:
Effect of HRT on triglyceride concentration at baseline and after 12 months of treatment (p < 0.0001)
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