Biomedical subjects

L Duchateau

Publications and source records attributed to L Duchateau.

At least 55 records · Page 3Linked to original sources

PubMed2003

Influence of acetylsalicylic acid and ketoprofen on canine thyroid function tests.

Many factors including drugs can influence thyroid function in humans, rats and dogs. Studies in humans report significant effects of non-steroidal anti-inflammatory agents (NSAIDs) on thyroid function tests, which can lead to misinterpretation of the results and inappropriate therapeutic decisions. As NSAIDs are used more and more frequently in dogs, it is important to know to what extent they can influence results. Eighteen spayed female beagle dogs were randomly assigned to three treatment sequences in a 3 x 3 crossover study design with treatments consisting of acetylsalicylic acid (ASA) (25 mg/kg BW q 12 h), ketoprofen (Keto) (1 mg/kg BW q 24 h) or placebo administered for a 1-week period with a 3-week washout period between treatment periods. Blood samples for determination of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), thyrotropin (TSH), reverse triiodothyronine (rT3), Keto and ASA concentrations were taken during each treatment period on days 0, 1, 3 and 7. During the washout period samples were taken weekly. A significant decrease in TT4 was observed as soon as 24 h after ASA administration, whereas the decrease in TT3 was less pronounced and differed significantly from the placebo only after 1 week of administration. No significant effects were found for free T4 and TSH with ASA administration. No significant effects on thyroid results were found following Keto administration. The results indicate that TT4 can be markedly decreased by ASA therapy and until the results of further studies are available, thyroid function test results should be interpreted cautiously in dogs on NSAIDs therapy.

Animals↗

PubMed2003

Longitudinal study on the prevalence of benzodiazepine (mis)use in a prison: importance of the analytical strategy.

AIMS: This study evaluates the suitability of gas chromatographic-mass spectrometric (GC-MS) analysis to follow-up the extent of benzodiazepine (mis)use in a Belgian prison population and compares it to other analytical strategies (e.g. screening followed by confirmation of the positive samples). DESIGN AND PARTICIPANTS: From February to August 1998, 598 persons were jailed of which 188 (31.4% of the incoming detainees) volunteered to be screened. Urine samples (530 in total) were collected on the day of arrival and after 14, 30 and 90 days of imprisonment. MEASUREMENTS: All samples were screened by EMIT(R) for benzodiazepines and analysed subsequently by GC-MS. FINDINGS: EMIT(R) screening yielded 117 (22.1%) positive samples, a number which increased to 174 (32.8%) after GC-MS analysis. Of these 174 GC-MS positive samples, 119 (68.4%) contained one benzodiazepine while for the remaining samples multiple benzodiazepine (mis)use could be demonstrated. A significant increase in benzodiazepine (mis)use was indicated only from day 0 to day 14 based on the GC-MS results but not on the immunoassay results, even when the latter were complemented with GC-MS analysis of the positively screened samples. The GC-MS data also demonstrated that benzodiazepines are mainly (mis)used by subjects on benzodiazepine prescription as almost 50% of these subjects took additional non-prescribed benzodiazepines. During GC-MS analysis other drugs were co-extracted unintentionally and chromatographed and 23.9% of the volunteers were positive for illegal drugs on the day of arrival. CONCLUSION: Immunoassay results yield an underestimation of the problem of benzodiazepine (mis)use in prison due to the high false negative rate. GC-MS analysis of all samples therefore is the recommended strategy for this type of longitudinal study as it yields more correct and detailed information than the immunoassay results.

Belgium↗

PubMed2003

Evaluation of thyroid function in obese dogs and in dogs undergoing a weight loss protocol.

Obesity and weight loss have been shown to alter thyroid hormone homeostasis in humans. In dogs, obesity is the most common nutritional problem encountered and weight loss is the cornerstone of its treatment. Therefore, it is important to clarify how obesity and weight loss can affect thyroid function test results in that species. The objectives of this study were to compare thyroid function in obese dogs and in lean dogs and to explore the effects of caloric restriction and weight loss on thyroid hormone serum concentrations in obese dogs. In the first experiment, 12 healthy lean beagles and 12 obese beagles were compared. Thyroid function was evaluated by measuring serum concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), thyrotropin (TSH), and reverse triiodothyronine (rT3) as well as a TSH stimulation test using 75 microg i.v. of recombinant human TSH. In the second experiment, eight obese beagles were fed an energy-restricted diet [average 63% maintenance energy requirement (MER)] until optimal weight was obtained. Blood samples for determination of TT4, FT4, TT3, TSH and rT3, were taken at the start and then weekly during weight loss. Only TT3 and TT4 serum concentrations were significantly higher in obese dogs as compared to lean dogs. In the second experiment, weight loss resulted in a significant decrease in TT3 and TSH serum concentrations. Thus obesity and energy restriction significantly alter thyroid homeostasis in dogs, but the observed changes are unlikely to affect interpretation of thyroid function test results in clinics.

Animals↗

PubMed2003

Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer.

BACKGROUND: Women with hormone-responsive metastatic breast cancer (MBC) may respond to or have stable disease with a number of hormone therapies. We explored the efficacy and safety of the steroidal aromatase inactivator exemestane as first-line hormonal therapy in MBC in postmenopausal women. PATIENTS AND METHODS: Patients with measurable disease were eligible if they had received no prior hormone therapy for metastatic disease and had hormone receptor positive disease or hormone receptor unknown disease with a long disease-free interval from adjuvant therapy. They were randomized to tamoxifen 20 mg/day or exemestane 25 mg/day in this open-label study. RESULTS: Blinded independently reviewed response rates for exemestane and tamoxifen were 41% and 17%, respectively. Fifty-seven per cent of exemestane- and 42% of tamoxifen-treated patients experienced clinical benefit, defined as complete or partial response, or disease stabilization lasting at least 6 months. There was a low incidence of severe flushing, sweating, nausea and edema in women who received exemestane. One exemestane-treated patient had a pulmonary embolism with grade 4 dyspnea. CONCLUSIONS: Exemestane is well tolerated and active in the first-line treatment of hormone-responsive MBC. An ongoing EORTC phase III trial is comparing the efficacy, measuring time-to-disease progression, of exemestane and tamoxifen.

Adult↗

PubMed2003

L-selectin and beta2-integrin expression on circulating bovine polymorphonuclear leukocytes during endotoxin mastitis.

The aim of this in vivo study was to examine the effect of intramammarily administered endotoxin (lipopolysaccharide, LPS) on the expression of L-selectin (CD62L) and the beta2-integrin subunits CD11b and CD18 on circulating bovine PMN. Six early lactating cows were infused with Escherichia coli LPS. The adhesion molecules under study were stained at the cell surface and analyzed flow cytometrically. In addition, some of the clinical parameters associated with adhesion molecule mobilization such as fever, blood cortisol levels, somatic cell count (SCC), and total and differential blood leukocyte count were measured. In analogy with observations during clinical coliform mastitis, a progressive decrease of CD62L expression levels was observed early after LPS infusion, concomitantly with a continuous rise of CD11b and CD18 density. However, no correlation was found between the kinetics of CD11b and CD18 density. The initial changes in adhesion molecule expression paralleled the decrease in blood PMN numbers, together with the increase in rectal temperature, cortisol levels, SCC, and number of circulating immature PMN. In conclusion, intramammarily administered LPS seems to play an important role in modulating adhesion receptor expression on circulating bovine PMN. Interestingly, in contrast to coliform mastitis, the net CD18 variation is not principally influenced by CD11b upregulation during endotoxin administration. The knowledge of adhesion molecule kinetics in relation to the different parameters evaluated in the present study contributes to an improved understanding of the inflammatory reaction.

Animals↗

PubMed2002

Different kinetic of antibody responses following infection of newly weaned pigs with an F4 enterotoxigenic Escherichia coli strain or an F18 verotoxigenic Escherichia coli strain.

To develop a vaccine against Escherichia coli-induced post-weaning diarrhea and edema disease, insights in the induction of the protective immune response following infection with these pathogenic E. coli is needed. Therefore, the fimbriae-specific antibody response of newly weaned pigs following infection with the Shiga-like toxin type II variant (SLT-IIv) producing F18(+) verotoxigenic E. coli (VTEC) (strain 107/86) was compared with the response following an infection with LT producing F4(+) enterotoxigenic E. coli (ETEC) (strain GIS 26). F4(+) ETEC were able to colonize the gut very soon after infection, as peak excretion of F4(+) E. coli bacteria was seen 2 days post-infection (dpi), but had already disappeared 7dpi. On the other hand, F18(+) VTEC infection resulted in a slower colonization of the gut as the peak excretion of F18(+) E. coli was observed between 3 and 5dpi, but this colonization remained longer as F18(+) E. coli were detected till 9dpi in feces. Furthermore, this fast colonization pattern of F4(+) ETEC is accompanied with the presence of F4-specific antibodies in mucosal tissues and serum from 4dpi onward, with maximal amounts of F4-specific IgA in the jejunal lamina propria and serum 7dpi. In contrast, F18-specific IgA was only readily detected in the jejunal lamina propria 15dpi and showed a maximum serum titer 21dpi. Besides this faster induction and higher antibody response, the switch from IgM to IgA and IgG was also earlier following the F4(+) ETEC infection.

Animals↗

PubMed2002

Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial.

PURPOSE: To compare the efficacy and tolerability of the combination of doxorubicin and paclitaxel (AT) with a standard doxorubicin and cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Eligible patients were anthracycline-naive and had bidimensionally measurable metastatic breast cancer. Two hundred seventy-five patients were randomly assigned to be treated with AT (doxorubicin 60 mg/m(2) as an intravenous bolus plus paclitaxel 175 mg/m(2) as a 3-hour infusion) or AC (doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2)) every 3 weeks for a maximum of six cycles. A paclitaxel (200 mg/m(2)) and cyclophosphamide (750 mg/m(2)) dose escalation was planned at cycle 2 if no grade >or= 3 neutropenia occurred in cycle 1. The primary efficacy end point was progression-free survival (PFS). Secondary end points were response rate (RR), safety, overall survival (OS), and quality of life. RESULTS: A median number of six cycles were delivered in the two treatment arms. The relative dose-intensity and delivered cumulative dose of doxorubicin were lower in the AT arm. Dose escalation was only possible in 17% and 20% of the AT and AC patients, respectively. Median PFS was 6 months in the two treatments arms. RR was 58% versus 54%, and median OS was 20.6 versus 20.5 months in the AT and AC arms, respectively. The AT regimen was characterized by a higher incidence of febrile neutropenia, 32% versus 9% in the AC arm. CONCLUSION: No differences in the efficacy study end points were observed between the two treatment arms. Treatment-related toxicity compromised doxorubicin-delivered dose-intensity in the paclitaxel-based regimen

Adult↗

PubMed2002

Treatment outcome studies. pitfalls in current methods and practice.

The objective of a treatment outcome study is to investigate the heterogeneity in outcome between patients according to factors other than treatment, such as country, institution or physician. Results of treatment outcome studies have already been extensively presented in the medical literature. However, no clear methodology has emerged to perform treatment outcome studies and various methods have been used. This paper reviews the different types of questions addressed in treatment outcome studies, the different methodologies and the different endpoints used. Statistical techniques are mainly descriptive including tables, estimates of survival curves, but regression models have also been used. Most of the studies use registry data, while only a few use discharge data or data available from clinical trials.

Clinical Trials as Topic↗

PubMed2001

Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902.

PURPOSE: To evaluate whether preoperative neoadjuvant chemotherapy in patients with primary operable breast cancer results in better overall survival (OS) and relapse-free survival rates and whether preoperative chemotherapy permits more breast-conserving surgery procedures than postoperative chemotherapy. PATIENTS AND METHODS: Six hundred ninety-eight breast cancer patients (T1c, T2, T3, T4b, N0 to 1, and M0) were enrolled onto a randomized phase III trial that compared four cycles of fluorouracil, epirubicin, and cyclophosphamide administered preoperatively versus the same regimen administered postoperatively (the first cycle administered within 36 hours after surgery). Patients were followed up for OS, progression-free survival (PFS), and locoregional recurrence (LRR). RESULTS: At a median follow-up of 56 months, there was no significant difference in terms of OS (hazards ratio, 1.16; P =.38), PFS (hazards ratio, 1.15; P =.27), and time to LRR (hazards ratio, 1.13; P =.61). Fifty-seven patients (23%) were downstaged by the preoperative chemotherapy, whereas 14 patients (18%) underwent mastectomy and not the planned breast-conserving therapy. CONCLUSION: The use of preoperative chemotherapy yields similar results in terms of PFS, OS, and locoregional control compared with conventional postoperative chemotherapy. In addition, preoperative chemotherapy enables more patients to be treated with breast-conserving surgery. Because preoperative chemotherapy does not improve disease outcome compared with postoperative chemotherapy, future trials should involve quality-of-life studies to investigate whether patients will benefit from this treatment modality.

Aged↗

PubMed2001

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.

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 (< or = 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 risk of invasive recurrence was not related to the histologic type of DCIS (P =.63), but the risk of distant metastasis was significantly higher in poorly differentiated DCIS compared with well-differentiated DCIS (hazard ratio, 6.57; P =.01). CONCLUSION: Patients with poorly differentiated DCIS have a high risk of distant metastasis after invasive local recurrence. Margin status is the most important factor in the success of BCT for DCIS; additionally, young age and symptomatic detection of DCIS have negative prognostic value.

Adult↗

PubMed2001

Breast-conserving therapy for Paget disease of the nipple: a prospective European Organization for Research and Treatment of Cancer study of 61 patients.

BACKGROUND: The purpose of the current study was to assess the outcome of breast-conserving therapy by means of a cone excision and radiotherapy in patients with Paget disease of the nipple without associated invasive breast carcinoma. METHODS: Between 1987 and 1998, 61 eligible patients were registered in the European Organization for Research and Treatment of Cancer Study 10873. The majority of patients (97%) presented without an associated palpable mass. At histologic examination, the majority (93%%) of patients had an underlying ductal carcinoma in situ (DCIS); in the remaining 7%, only Paget disease was found. Treatment was comprised of a complete excision of the nipple-areolar complex including the underlying breast tissue with tumor free margins, followed by external irradiation to the whole breast (50 gray in 25 fractions). The primary endpoint was local recurrence. RESULTS: At a median follow-up of 6.4 years, 4 of the 61 patients developed a recurrence in the treated breast (1 patient with DCIS and 3 patients with invasive disease). One patient with an invasive local recurrence died of disseminated breast carcinoma. The 5-year local recurrence rate was 5.2% (95% confidence interval, 1.8-14.1%). CONCLUSIONS: Breast-conserving therapy is a feasible alternative for patients with Paget disease and a limited extent of underlying DCIS. To achieve good local control, treatment should be comprised of a complete excision of the nipple-areolar complex including the underlying disease, followed by irradiation to the whole breast.

Adult↗

PubMed2001

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.

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 randomizing 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-up 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.

Antineoplastic Agents, Hormonal↗

PubMed2001

Individual patient-versus literature-based meta-analysis of survival data: time to event and event rate at a particular time can make a difference, an example based on head and neck cancer.

The objective of this study is to compare the results of an individual patient-based and a literature-based meta-analysis in chemotherapy in head and neck cancer and to identify the sources of difference. For all head and neck cancer randomized controlled clinical trials comparing chemotherapy and loco-regional treatment with loco-regional treatment alone, both the literature data and the individual patient data are retrieved and meta-analyses performed and compared. Only survival data are used as outcome, although both time to death and mortality at specific time points are considered in different analyses. There are substantial differences between the individual patient-based and the literature-based meta-analyses. The most important reason for the differing results is that the individual patient-based meta-analysis is based on a time to event analysis, whereas the literature-based meta-analysis is based on mortality at a specific time point. Mortality can change substantially with follow-up time. The absolute survival differences in the case study, for instance, increase from 2.6% at 2 years to 5.6% at 5 years.

Antineoplastic Agents↗

PubMed2001

Improved survival after one course of perioperative chemotherapy in early breast cancer patients. long-term results from the European Organization for Research and Treatment of Cancer (EORTC) Trial 10854.

The aim of this study was to examine whether one course of perioperative polychemotherapy yields better results in terms of survival, progression-free survival (PFS) and locoregional control than surgery alone in early stage breast cancer. From 1986 to 1991, 2795 patients with stage I/II breast cancer were randomised to receive either one perioperative course of an anthracycline-containing chemotherapeutic regimen within 36 h after surgery or surgery alone. Patients were followed-up for overall survival, PFS and locoregional recurrence. The median follow-up period at time of the analysis was 11 years. PFS and locoregional control were significantly better (P=0.025 and P=0.004, respectively) in the perioperative chemotherapy arm. Node-negative patients seemed to benefit most from the perioperative FAC. Patients who received perioperative chemotherapy and locoregional therapy alone had significantly better overall survival rates than patients who received locoregional therapy alone (P=0.004). Patients who received additional systemic therapy did not seem to benefit from one course of perioperative chemotherapy (P=0.65). One course of perioperative polychemotherapy does improve PFS and locoregional control in early stage breast cancers. This effect is still present after 11 years of follow-up.

Adult↗

PubMed2001

Variations in diagnostic and therapeutic procedures in a multicentre, randomized clinical trial (EORTC 10853) investigating breast-conserving treatment for DCIS.

AIMS: To evaluate the diagnostic and therapeutic procedures which were followed in a European Organization for Research and Treatment of Cancer (EORTC) randomized clinical trial investigating the role of radiotherapy in breast-conserving treatment (BCT) for ductal carcinoma in situ (DCIS) of the breast. METHODS: The medical files of 824 of the 1010 randomized patients (82%) were reviewed during site visits to 30 participating institutes. RESULTS: Large variations occurred, particularly in the surgical procedures and histopathological work-up which were performed. Important risk factors like tumour size and margin status were poorly quantified in the medical files. CONCLUSIONS: These findings emphasize the need for establishing uniform guidelines for diagnostic and therapeutic procedures for DCIS, and for clearly defined risk factors for recurrence after BCT for DCIS. Because of its randomized nature, the main question of the trial, i.e. the effect of radiotherapy on the risk of local recurrence, will not be influenced by variation. The risk of local recurrence in itself, and hence the success of BCT for DCIS, may however be influenced by the quality of the initial procedures that were conducted.

Breast Neoplasms↗

PubMed2001

Histological type and marker expression of the primary tumour compared with its local recurrence after breast-conserving therapy for ductal carcinoma in situ.

We have investigated primary ductal carcinomas in situ (DCIS) of the breast and their local recurrences after breast-conserving therapy (BCT) for histological characteristics and marker expression. Patients who were randomized in the EORTC trial 10853 (wide local excision versus excision plus radiotherapy) and who developed a local recurrence were identified. Histology was reviewed for 116 cases; oestrogen and progesterone receptor status, and HER2/ neu and p53 overexpression were assessed for 71 cases. Comparing the primary DCIS and the invasive or non-invasive recurrence, concordant histology was found in 62%, and identical marker expression in 63%. Although 11% of the recurrences developed at a distance from the primary DCIS, nearly all these showed the same histological and immunohistochemical profile. 5 patients developed well-differentiated DCIS or grade I invasive carcinoma after poorly differentiated DCIS. Although these recurrences occurred in the same quadrant as the primary DCIS, they may be considered as second primary tumours. Only 4 patients developed poorly differentiated DCIS or grade III invasive carcinoma after well differentiated DCIS. We conclude that in most cases the primary DCIS and its local recurrence are related histologically or by marker expression, suggesting that local recurrence usually reflects outgrowth of residual DCIS; progression of well differentiated DCIS towards poorly differentiated DCIS or grade III invasive carcinoma is a non-frequent event.

Adult↗

PubMed2001

Taxanes in the adjuvant treatment of breast cancer: why not yet?

The taxanes paclitaxel and docetaxel represent the most active chemotherapeutic agents developed for the treatment of advanced breast cancer in the last decade, and they are now being incorporated into adjuvant chemotherapy trials for lymph node-positive breast cancer with the hope of improving on the results achieved with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) or anthracycline-based regimens. So far, three randomized paclitaxel-based adjuvant clinical trials enrolling 3170 women (Cancer and Leukemia Group B [CALGB] 9344), 3060 women (National Surgical Adjuvant Project for Breast and Bowel Cancers [NSABP]-B28), and 524 women (M. D. Anderson), respectively, have been reported with respective median follow-up times of 52, 34, and 43 months. This article critically reviews these three studies and gives an overview of the many other randomized clinical trials, due to accrue more than 17 000 women, which are investigating the potential of taxanes in adjuvant breast cancer therapy. Given that the early promise of taxanes suggested by CALGB 9344 is not yet confirmed by the two other trials, only level 2 evidence has been reached to date in regard to a positive contribution of these agents to breast cancer outcome in the adjuvant setting. It is argued that level 1 evidence is highly desirable before adopting taxane-based regimens in standard practice. It is anticipated that a meta-analysis will be needed to comprehensively define the value of taxanes in early breast cancer, and a new model of international collaboration is proposed to find a balance between the need to offer new, more effective therapies to patients as soon as possible and the danger of drawing wrong, premature conclusions regarding the magnitude of benefit of a new regimen.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Combined treatment with buserelin and tamoxifen in premenopausal metastatic breast cancer: a randomized study.

BACKGROUND: 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.

Adult↗