lhrh--ala(6)-gly(10)-ethylamide- and Breast-Neoplasms

The role of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. We conducted a systematic review and meta-analysis of randomized trials evaluating the efficacy of GnRHa, given before and during chemotherapy, in the prevention of POF in premenopausal cancer patients.. Studies were retrieved by searching PubMed, Web of Knowledge database and the proceedings of major conferences. We calculated Odds Ratios (OR) and 95% confidence intervals (CIs) for POF from each trial and obtained pooled estimates through the random effects model as suggested by DerSimonian and Laird.. Nine studies were included in the meta-analysis with 225 events of POF occurring in 765 analyzed patients. The pooled OR estimate indicates a highly significant reduction in the risk of POF (OR=0.43; 95% CI: 0.22-0.84; p=0.013) in patients receiving GnRHa. There was statistically significant heterogeneity among studies (I(2)=55.8%; p=0.012). There was no evidence of publication bias. Subgroups analyses showed that the protective effect of GnRHa against POF was similar in subgroups of patients defined by age and timing of POF assessment, while it was present in breast cancer but unclear in ovarian cancer and lymphoma patients.. Our pooled analysis of randomized studies shows that the temporary ovarian suppression induced by GnRHa significantly reduces the risk of chemotherapy-induced POF in young cancer patients.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Gonadotropin-Releasing Hormone; Hodgkin Disease; Humans; Patient Safety; Premenopause; Primary Ovarian Insufficiency; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome; Young Adult

Patients with large ER positive tumors candidate to preoperative chemotherapy may also benefit from a concurrent endocrine intervention, but this issue has been scarcely investigated due to concerns arising from unfavorable results emerged from an adjuvant trial of concurrent tamoxifen and chemotherapy. We retrospectively investigated the activity of letrozole plus GnRH analogue (GnRH-a) administered concurrently with preoperative chemotherapy and as adjuvant treatment in premenopausal women with locally advanced ER positive breast cancer consecutively admitted at the European Institute of Oncology. Results were compared with those of a non-randomized unmatched control group of premenopausal women with locally advanced ER positive breast cancer receiving preoperative chemotherapy, followed by tamoxifen and GnRH-a after surgery. Primary endpoints were pathological complete response (pCR) rate, decrease of Ki67 and disease free survival (DFS). One-hundred and nineteen women constituted the study group, while 95 patients served as controls. The pCR rate was 5.0 vs 1.1% in the study and control group, respectively. A statistically significant greater suppression of Ki67 was observed in patients receiving chemoendocrine therapy as compared with controls (P = 0.003). At a median follow up of 59 months, 26 events occurred in the chemoendocrine group and 48 in the control group. Five-year DFS was 78 vs 41% in the study and in the control group, respectively [adjusted HR 0.46, 95% CI 0.27-0.79, P = 0.0047]. The concurrent administration of letrozole and GnRH-a with preoperative chemotherapy was highly effective in premenopausal women with large ER positive breast cancer in terms of decreased proliferation and of improved DFS. Randomized studies are warranted to establish the role of the addition of endocrine therapy to chemotherapy as standard preoperative approach for ER positive locally advanced breast cancer as well as of letrozole in combination with GnRH-a for the treatment of premenopauasal women with early breast cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Disease-Free Survival; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Ki-67 Antigen; Letrozole; Middle Aged; Neoadjuvant Therapy; Nitriles; Premenopause; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Treatment Outcome; Triazoles