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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. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine risk factors for trocar implantation metastasis after diagnostic laparoscopy in patients with primary or recurrent advanced ovarian cancer.Study Design: Eighty-three women with primary advanced ovarian cancer and 21 women with recurrent ovarian cancer undergoing a laparoscopy for a tissue diagnosis and for assessment of operability were included in the study. The occurrence of implantation metastasis at the trocar incision scars was analyzed according to clinicopathologic characteristics.Results: A recurrence developed at the trocar site in 7 (58%) of 12 patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in 2 (2%) of 92 patients undergoing a laparoscopy with closure of all layers (odds ratio, 63; 95% confidence interval, 10.3-385; P <.001). The International Federation of Gynecology and Obstetrics stage at initial presentation, tumor histologic type, tumor differentiation, maximal tumor diameter at the time of diagnosis, estimated weight of the metastatic tumor, residual tumor after cytoreductive surgery, surgical characteristics, and type of chemotherapy were well balanced among both groups. Patients with implantation metastasis had significantly more ascites (median, 700 mL vs 300 mL; P =.032) and a longer interval between the start of platinum-based chemotherapy or cytoreductive surgery (median, 6 days vs 17 days; P <.01) compared with patients without abdominal wall recurrence. A palpable abdominal wall metastasis developed in none of the patients undergoing a laparoscopy with closure of all layers of the abdomen followed by cytoreductive surgery or chemotherapy within 1 week after the laparoscopy. Kaplan-Meier survival analysis showed that patients with abdominal wall implantation metastasis had a survival rate similar to that of the other patients.Conclusions: Laparoscopy with careful closure of the peritoneum, rectus sheath, and skin followed by chemotherapy or cytoreductive surgery with excision of the trocar trajectories within 1 week is safe in patients with disseminated ovarian cancer. [ABSTRACT FROM AUTHOR]

Fulvestrant (Faslodex) is a new estrogen receptor (ER) antagonist with no agonist effects that is licensed for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer (ABC) who have progressed/recurred on prior antiestrogen therapy. The Faslodex Compassionate Use Program (CUP) provides expanded access to fulvestrant in countries where it is not yet available for patients who are not eligible to enter clinical trials. This analysis pools data from 402 patients who received fulvestrant as part of the CUP in Belgium, predominantly as 3rd- to 5th-line endocrine therapy for ABC. Two patients experienced partial responses and 118 experienced stable disease lasting>or=6 months, resulting in an overall clinical benefit rate of 29.9%. Fulvestrant was active in patients with multiple sites of metastases, visceral metastases, human epidermal growth factor receptor 2-positive disease and after heavy endocrine pre-treatment. Fulvestrant was well tolerated, with only six patients (1.5%) discontinuing treatment following adverse events. These data support the findings of previous CUP analyses and Phase II and III trials, suggesting that fulvestrant is a valuable addition to the treatment sequence for postmenopausal women with ABC who have progressed/recurred on prior endocrine therapy.

Purpose: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer., Patients and Methods: This multicenter phase III trial randomly assigned 916 patients with hormone receptor-positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician's discretion. This report updates efficacy at a median follow-up of 32 months., Results: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P <.0001), time to treatment failure (median, 9 v 5.7 months, respectively; P <.0001), overall objective response rate (32% v 21%, respectively; P =.0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P =.001)., Conclusion: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.