Luc Duchateau

Bio: Luc Duchateau is an academic researcher from Ghent University. The author has contributed to research in topics: Metastatic breast cancer & Malaria. The author has an hindex of 33, co-authored 87 publications receiving 5157 citations. Previous affiliations of Luc Duchateau include Université catholique de Louvain & European Organisation for Research and Treatment of Cancer.

Severity of E. coli mastitis is mainly determined by cow factors

Abstract: Intramammary infections of dairy cows with Gram-positive bacteria such as Staphylococcus aureus (major cause of mastitis) have received a lot of attention because of their major economic impact on the dairy farm through production losses induced by an increase in somatic cell count. Management strategies, including greater awareness for efficient milking and hygienic measures, have limited the spread of Gram-positive bacteria and resulted in a significant decrease of proportion of S. aureus isolates and subclinical mastitis worldwide. Other organisms such as coliform subspecies and Streptococcus uberis, both environmental bacteria that cause clinical mastitis, have received less attention. Escherichia coli causes inflammation of the mammary gland in dairy cows around parturition and during early lactation with striking local and sometimes severe systemic clinical symptoms. This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases. It is well known that bacterial, cow and environmental factors are interdependent and influence mastitis susceptibility. Many studies, executed during the last decade, indicate that the severity of E. coli mastitis is mainly determined by cow factors rather than by E. coli pathogenicity. During E. coli mastitis, the host defense status is a cardinal factor determining the outcome of the disease. Today, we know that the neutrophil is a key factor in the cows' defense against intramammary infection with E. coli. Effective elimination of the pathogen by neutrophils is important for the resolution of infection and the outcome of E. coli mastitis. This review is a compilation of some major findings over the last 15 years concerning mainly host factors that modulate and influence neutrophil function and the mammary inflammatory reaction. The individual chapters address: virulence factors of E. coli strains, how neutrophils kill E. coli, connection between endotoxins, tumor necrosis factor-alpha and nitric oxide, severity classification of E. coli mastitis, lifespan of neutrophils, host factors that influence severity, tissue damage and production loss.

Risk Factors for Recurrence and Metastasis After Breast-Conserving Therapy for Ductal Carcinoma-In-Situ: Analysis of European Organization for Research and Treatment of Cancer Trial 10853

Abstract: PURPOSE: In view of the increasing number of patients treated with breast-conserving treatment (BCT) for ductal carcinoma-in-situ (DCIS), risk factors for recurrence and metastasis should be identified. PATIENTS AND METHODS: Clinical and pathologic characteristics from patients with DCIS in the European Organization for Research and Treatment of Cancer trial 10853 (excision with or without radiotherapy) were related to the risk of recurrence. Pathologic features were derived from a central review of 863 of the 1,010 randomized cases (85%). The median follow-up was 5.4 years. RESULTS: Factors associated with an increased risk of local recurrence in the multivariate analysis were young age (≤ 40 years) (hazard ratio, 2.14; P = .02), symptomatic detection of DCIS (hazard ratio, 1.80; P = .008), growth pattern (solid and cribriform) (hazard ratios, 2.67 and 2.69, respectively; P = .012), involved margins (hazard ratio, 2.07; P = .0008), and treatment by local excision alone (hazard ratio, 1.74; P = .009). The...

The Frailty Model

Abstract: Readers will find in the pages of this book a treatment of the statistical analysis of clustered survival data. Such data are encountered in many scientific disciplines including human and veterinary medicine, biology, epidemiology, public health and demography. A typical example is the time to death in cancer patients, with patients clustered in hospitals. Frailty models provide a powerful tool to analyze clustered survival data. In this book different methods based on the frailty model are described and it is demonstrated how they can be used to analyze clustered survival data. All programs used for these examples are available on the Springer website.

Combined Tamoxifen and Luteinizing Hormone-Releasing Hormone (LHRH) Agonist Versus LHRH Agonist Alone in Premenopausal Advanced Breast Cancer: A Meta-Analysis of Four Randomized Trials

Abstract: Purpose: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. Patients and Methods: Four clinical trials randomising a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials. Results: With a median follow-vp of 6.8 years, there was a significant survival benefit (stratified log-rank test, P =.02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P =.0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P =.03; odds ratio = 0.67). Conclusion: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment. J Clin Oncol 19:343-353. (C) 2001 by American Society of Clinical Oncology.

Combined Treatment With Buserelin and Tamoxifen in Premenopausal Metastatic Breast Cancer: a Randomized Study

Abstract: textBACKGROUND: Surgical or medical castration and antiestrogenic treatment with tamoxifen are common endocrine treatments for premenopausal women with breast cancer. However, tamoxifen therapy induces high levels of plasma estradiol, with unknown long-term effects. In this study, we investigated the effect of combining estrogen suppression with the luteinizing hormone-releasing hormone agonist buserelin and estradiol receptor blockade with tamoxifen to determine whether the high estradiol levels induced by tamoxifen could be reduced and whether the antitumor effects would be better. METHODS: In a three-arm, randomized, prospective trial, from 1988 through 1995, a total of 161 premenopausal patients with advanced breast cancer were randomly assigned to treatment with buserelin, tamoxifen, or both. Patients with steroid receptor-negative tumors or with tumors of unknown receptor status who had a disease-free interval of less than 2 years were excluded. The median follow-up was 7.3 years, during which 76% of the patients died, all of breast cancer. Patient and tumor characteristics were well balanced among treatment groups. All P values are from two-sided tests. RESULTS: Combined treatment with buserelin and tamoxifen was superior to treatment with buserelin or tamoxifen alone by objective response rate (48%, 34%, and 28% of patients who could be evaluated, respectively; P =.11 [chi(2) test]), median progression-free survival (9.7 months, 6.3 months, and 5.6 months; P =.03), and overall survival (3.7 years, 2.5 years, and 2.9 years; P =.01). Actuarial 5-year survival percentages were 34.2% (95% confidence interval [CI] = 20.4%-48.0%), 14.9% (95% CI = 3.9%-25.9%), and 18.4% (95% CI = 7.0%-29.8%), respectively. No differences in antitumor effects were observed between single-agent treatment groups. During combined treatment or treatment with buserelin alone, plasma estradiol levels were suppressed equally; in contrast, during treatment with tamoxifen alone, plasma estradiol levels increased threefold to fourfold over pretreatment levels. CONCLUSION: Combined treatment with buserelin and tamoxifen was more effective and resulted in longer overall survival than treatment with either drug alone.

Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity

Abstract: The clinical use of anthracyclines like doxorubicin and daunorubicin can be viewed as a sort of double-edged sword. On the one hand, anthracyclines play an undisputed key role in the treatment of many neoplastic diseases; on the other hand, chronic administration of anthracyclines induces cardiomyopathy and congestive heart failure usually refractory to common medications. Second-generation analogs like epirubicin or idarubicin exhibit improvements in their therapeutic index, but the risk of inducing cardiomyopathy is not abated. It is because of their janus behavior (activity in tumors vis-a-vis toxicity in cardiomyocytes) that anthracyclines continue to attract the interest of preclinical and clinical investigations despite their longer-than-40-year record of longevity. Here we review recent progresses that may serve as a framework for reappraising the activity and toxicity of anthracyclines on basic and clinical pharmacology grounds. We review 1) new aspects of anthracycline-induced DNA damage in cancer cells; 2) the role of iron and free radicals as causative factors of apoptosis or other forms of cardiac damage; 3) molecular mechanisms of cardiotoxic synergism between anthracyclines and other anticancer agents; 4) the pharmacologic rationale and clinical recommendations for using cardioprotectants while not interfering with tumor response; 5) the development of tumor-targeted anthracycline formulations; and 6) the designing of third-generation analogs and their assessment in preclinical or clinical settings. An overview of these issues confirms that anthracyclines remain "evergreen" drugs with broad clinical indications but have still an improvable therapeutic index.

A Randomized Trial Of Exemestane After Two To Three Years Of Tamoxifen Therapy In Postmenopausal Women With Primary Breast Cancer.

Abstract: background Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor–positive breast cancer. Despite this treatment, however, some patients have a relapse. methods We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival. results Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported — 183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04). conclusions Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.

Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer

Abstract: BackgroundGrowth of hormone-receptor–positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1 phase to the S phase of the cell cycle. We assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer. MethodsThis phase 3 study involved 521 patients with advanced hormone-receptor–positive, human epidermal growth factor receptor 2–negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. Premenopausal or perimenopausal women also received goserelin. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee af...