ABSTRACT
Background: Preclinical evidence suggests a possible negative impact of deleterious BRCA mutations on female fertility. However, limited and rather conflicting clinical data are available. This study assessed the reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients. Patients and methods: This was a retrospective analysis of two prospective studies investigating oocyte cryopreservation and ovarian tissue cryopreservation in newly diagnosed early breast cancer patients. In the current analysis, baseline anti-Mullerian hormone (AMH) and performance of cryopreservation strategies were compared between patients with or without germline deleterious BRCA mutations. Results: Out of 156 patients included, 101 had known BRCA status of whom 29 (18.6%) were BRCA-mutated and 72 (46.1%) had no mutation. Median age in the entire cohort was 31 years [interquartile range (IQR) 28-33). Median AMH levels were 1.8 µg/l (IQR 1.0-2.7) and 2.6 µg/l (IQR 1.5-4.1) in the BRCA-positive and BRCA-negative cohorts, respectively (P = 0.109). Among patients who underwent oocyte cryopreservation (N = 29), women in the BRCA-positive cohort tended to retrieve (6.5 versus 9; P = 0.145) and to cryopreserve (3.5 versus 6; P = 0.121) less oocytes than those in the BRCA-negative cohort. Poor response rate (i.e. retrieval of ≤4 oocytes) was 40.0% and 11.1% in the BRCA-positive and BRCA-negative cohorts, respectively (P = 0.147). Among patients who underwent ovarian tissue cryopreservation (N = 72), women in the BRCA-positive cohort tended to have a numerically lower number of oocytes per fragment (0.08 versus 0.14; P = 0.193) and per square millimeter (0.33 versus 0.78; P = 0.153) than those in the BRCA-negative cohort. Two BRCA-mutated patients were transplanted after chemotherapy and one delivered at term a healthy baby. No difference between BRCA1- and BRCA2-mutated patients was observed in any of the above-mentioned outcomes. Conclusion: A consistent trend for reduced reproductive potential and performance of cryopreservation strategies was observed in BRCA-mutated breast cancer patients. Independent validation of these results is needed.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/therapy , Cryopreservation/methods , Fertility Preservation/methods , Oocytes , Ovary , Adult , Female , Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Humans , Retrospective StudiesABSTRACT
OBJECTIVE: The aim of this study is to describe the evolution of therapeutic practices and the evolution of survival between 1982 and 1996 in a population of ovarian carcinomas. All the patients were registered in the "Registre des Cancers Gynécologiques de Côte-d'Or-France". POPULATION AND METHODS: During this period, 546 cases of ovarian cancers were registered. Data about FIGO staging at the diagnosis, histologic type, initial surgical procedures and survival were studied. RESULTS: During this period, 61.7% of the patients had a complete resection of their tumor. The frequency of complete removal increased significantly during the period of this study. Complete removal moved from 56%, between 1982 and 1984, up to 75%, between 1993 and 1996. Complete removal was possible in 98.1% of the FIGO stage 1 cases while it was possible in only 18.3% of the stage IV. 76.9% of the patients younger than 50 years old had a complete removal while only 29% of the women older than 80 years old had a complete removal. Fifty percent of stage I received chemotherapy as long as 85% of patients younger than 50 years old. After 1993, only 2.6% of them had radiotherapy. The global survival rate at 5 years was 35.4%. CONCLUSIONS: Surgery is the major procedure to obtain a complete remission of ovarian cancer. The efficacy of current chemotherapies may modify the initial management of these tumors, particularly in modifying the chronology of the different therapeutic sequences.
Subject(s)
Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Aged , Female , France , Humans , Middle Aged , Practice Patterns, Physicians' , Registries , Survival RateABSTRACT
BACKGROUND: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to beta-D-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a multicenter prospective phase II trial in recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent GBM following surgery, radiotherapy and no more than one prior line of chemotherapy. Patients were treated with glufosfamide 5000 mg/m(2) administered as a 1-h intravenous infusion. Treatment success was defined as patients with either an objective response according to Macdonald's criteria or 6 months progression-free survival. Toxicity was assessed with the Common Toxicity Criteria (CTC) version 2.0. RESULTS: Thirty-one eligible patients were included. Toxicity was modest, the main clinically relevant toxicities being leukopenia (CTC grade >3 in five patients) and hepatotoxicity (in three patients). No responses were observed; one patient (3%; 95% confidence interval 0 to 17%) was free from progression at 6 months. Pharmacokinetic analysis showed a 15% decrease in area under the curve and glufosfamide clearance in patients treated with enzyme-inducing antiepileptic drugs, but no effect of these drugs on maximum concentration and plasma half-life. CONCLUSION: Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GBM.