Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast cancer: a phase II pilot study

Abstract

The aim of the present trial was to investigate the protective effects on ovarian function, and the efficacy and tolerability of goserelin added to adjuvant chemotherapy for early breast cancer. Following surgical treatment, 64 premenopausal patients with early breast cancer received goserelin 3.6 mg (every 28 days for 1 year) and an adjuvant treatment which was chosen according to the patient's prognosis. Median age was 42 years (range 27-50). ECOG performance status was 0-1 in all patients. Twenty-eight patients (44%) had estrogen receptor (ER)+ tumors and 36 (56%) patients had ER- tumors. Fifty-two (81%) patients had stage II disease and 12 (19%) had stage III disease. Eighteen patients received cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, 46 patients received an anthracycline-based regimen, and nine of them received high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation. Fifty-one patients (80%) were irradiated. ER+ patients also received tamoxifen for 5 years. Serum estradiol was suppressed to values below 40 pg/ml in all patients. After a median follow-up of 55 months, 86% of patients had resumed normal menses, 84% of patients were disease-free and 94% were alive. The 1-, 3- and 5-year projected recurrence-free survival rates were 100, 81 and 75%, respectively. Five years after treatment one patient had a pregnancy that ended with a normal childbirth. No unexpected adverse events were reported. These data show that the addition of goserelin to adjuvant therapy of premenopausal patients with early breast cancer is well tolerated and protects long-term ovarian function.

How to Preserve Fertility in Young Women Exposed to Chemotherapy? The Role of GnRH Agonist Cotreatment in Addition to Cryopreservation of Embrya, Oocytes, or Ovaries

“…This difference may suggest a possible prolongation of the "fertility window" by 7 years (or more) using GnRH agonist adjuvant cotreatment in parallel with chemotherapy. This is in keeping with the experience reported by others [32,33] who also found the median age of pregnant survivors of lymphomas to be 18 years (range, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28], with only few reported pregnancies for female patients Ͼ30 years old.…”

“…All 13 patients in one study [24], aged 26 -39 years, resumed normal ovarian function after a mean of 4.9 months postchemotherapy, and in another study [25], 86% of the 64 premenopausal patients (27-50 years of age) resumed cyclic menstruation, despite a relatively advanced median age of 42 years. In a recent update of their previous study [25], Recchia et al [26] found that all their breast cancer patients younger than 40 who received GnRH agonist cotreatment in addition to chemotherapy resumed cyclic ovarian function, with excellent 5-and 10-year survival rates. In breast cancer, at least four phase II studies evaluated the activity of ovarian suppression with GnRH agonists in preserving fertility and ovarian function [24 -29].…”

Chemotherapy-Induced Amenorrhea and Fertility in Women Undergoing Adjuvant Treatment for Breast Cancer

“…Further investigation of GnRH analogues for this indication is warranted. 36 While a potential benefit has been suggested by these findings, benefit has not been confirmed in a larger trial with stratification for disease, age and type of therapy. In addition, the risk of chemotherapy-induced amenorrhea has not been clearly defined.…”

“…Another trial evaluating chemotherapyinduced amenorrhea in patients with lymphomas showed a protective effect of co-treatment with a GnRH agonist ( Table 4). 23 In a recently reported trial investi- gating the protective effects of goserelin on ovarian function, 36 premenopausal women received goserelin combined with various adjuvant chemotherapy regimens including CMF, CEF, and high-dose chemotherapy followed by bone marrow transplant as adjuvant treatment of breast cancer. The median age of the 64 women accrued to the trial was 42.…”

Ovarian recovery after stem cell transplantation

“…Further trials are needed to validate clinical potential of GnRH in the preservation of fertility. [17][18][19][20] In spite of the fact that almost all women who undergo BMT have developed an ovarian failure, recovery is possible. A large retrospective survey of fertility after SCT involving 37 362 patients revealed that only 0.6% of patients conceived after one autologous or allogeneic SCT.…”