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: 671 views

Related Articles

Lotfi Kochbati, Verna Vanderpuye, Rim Moujahed, Mouna Ben Rejeb, Zeineb Naimi, Tajudeen Olasinde
Annu Rajpurohit, Nilendu Purandare, Aliasgar Moiyadi, Prakash Shetty, Abhishek Mahajan, Rajiv Kumar, Subhash Yadav, Naveen Munmudi, Ameya Puranik, Anil Tibdewal, Rahul Krishnarthy, Ankita Ahuja, Nandini Menon, Vanita Noronha, Amit Joshi, Vijay M Patil, Kumar Prabhash
Mursheda Begum, Isobel Urquhart, Grant Lewison, Fouad Fouad, Richard Sullivan
Vittorio Gebbia, Marco Maria Aiello, Giuseppe Banna, Giusi Blanco, Livio Blasi, Nicolò Borsellino, Dario Giuffrida, Mario Lo Mauro, Gianfranco Mancuso, Dario Piazza, Giuseppina Savio, Hector Soto Parra, Maria Rosaria Valerio, Francesco Verderame, Paolo Vigneri
Moises S Martins Lopes, Larissa M Machado, Pedro A Ismael Amaral Silva, Angel A Tome Uchiyama, Cheng T Yen, Eliza D Ricardo, Taciana S Mutao, Jefferson R Pimento, Jefferson R Pimenta, Denis S Shimba, Rodrigo M Hanriot, Renata D Peixoto