The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'.

BACKGROUND: The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase II trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged. RESULTS: Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A1, Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo A1, Apo B and Lip a levels to allow for assessment of E's impact on these subsets. The atherogenic risk determined by Apo A1:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms. CONCLUSIONS: Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E's excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.

Project Manager

Le projet de construction au XXIe siècle :nouveaux acteurs, nouvelles responsabilités. L’apparition de nouveaux intervenants dans les projets de contruction bouleverse le schéma classique Maître d’ouvrage – Architecte – Entrepreneur. Parmi ceux-ci, le Project Manager occupe une place de premier rang, dès lors qu’il interviendra bien souvent dès l’entame du projet et jusqu’à complétion de celui-ci. L’ouvrage offre une première analyse complète de sa situation juridique, en mêlant littérature juridique (belge, française et américaine) et pratique de terrain. Envisagé ici à travers le prisme de sa relation contractuelle avec le Maître d’ouvrage, le Project manager reçoit une définition légale d’où sont déduits les éléments essentiels de se son contrat. Son statut, ses missions ainsi que ses responsabilités sont identiés précisément et articulés harmonieusement avec ceux d’autre professionnels (arhitectes et entrepreneurs). Spécialement sur la question des reponsabilités, l’ouvrage démontre que certains cas de responsabilité traditionnellement imputés à l’un de ces autres acteurs pourront être imputés au Project Manager, allant dans le sens d’un régime unifié de responsabilité pour l’ensemble de ces acteurs. L’ouvrage s’enrichit encore d’un modèle contractuel de base et d’une bibliographie.Incontestablement, l’ouvrage vient combler un vide doctrinal et constituera un guide essentiel, tant pour les Maîtres d’ouvrage que pour les Project Manager.