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

6 Feb 2008
M Lazzeroni, D Macis, A Decensi, S Gandini, M Teresa Sandri, D Serrano, A Guerrieri-Gonzaga, H Johansson, S Mora, C Daldoss, U Omodei, B Bonanni

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) Circulation 106 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.

Article metrics: 646 views

Related Articles

Luis Larrea, Enrique López, Paola Antonini, Verónica González, Miguel Ángel Berenguer, Maria Carmen Baños, Jose Bea, Jose Domingo
Akhil Kapoor, Vanita Noronha, Vijay M Patil, Amit Joshi, Nandini Menon, Abhishek Mahajan, Amit Janu, Kumar Prabhash
Muhammad Shahid Iqbal, Joseph Carlow, Fiona McDonald, Philip Atherton, Helen Turnbull, Sandeep Singhal, Timothy Simmons, Paula Mulvenna, Josef Kovarik, Rhona McMenemin, Jill Gardiner, Alastair Greystoke
Viviane Teixeira Loiola de Alencar, Maria Nirvana Formiga, Vladmir Cláudio Cordeiro de Lima
Guilherme Harada, Fernando Costa Santini, Felipe Sales Nogueira Amorim Canedo, Leandro Jonata de Carvalho Oliveira, Henrique Bortot Zuppani, Gilberto de Castro Jr