Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China

Purpose Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer. Patients and Methods Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels. Results Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status. Conclusion When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.

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Tactics for minimizing risk of increasing estradiol against the background of aromatase inhibitors in combination with gonadotropin releasing hormone agonists in adjuvant therapy for breast cancer in premenopausal patients. Pilot study results

Medical Council ◽

10.21518/2079-701x-2018-19-76-84 ◽

2018 ◽

pp. 76-84

Author(s):

I. B. Kononenko ◽

A. V. Snegovoi ◽

L. V. Manzyuk ◽

E. I. Kovalenko ◽

V. Yu. Selchuk

Keyword(s):

Breast Cancer ◽

Menstrual Cycle ◽

Adjuvant Therapy ◽

Aromatase Inhibitors ◽

Ovarian Function ◽

Reproductive Hormones ◽

Gonadotropin Releasing Hormone ◽

Gnrh Analogues ◽

Releasing Hormone ◽

Premenopausal Patients

Aromatase inhibitor (AI) combined with Gonadotropin-releasing hormone agonist (GnRH-a) have been recognized as an effective approach to adjuvant endocrinotherapy for breast cancer (BC) in premenopausal patients with adverse predictive factors. However, the risk of non-optimal suppression of the ovaries due to the mechanism of action of aromatase inhibitors has been proven. Recently published SOFT-EST studies showed that the blood estradiol (E2) level in 37% of patients was above the level that was permissible for the purpose of this group of drugs. And although today there is no enough scientific justification to interpret this result, the introduction of aromatase inhibitors in adjuvant therapy in young women requires the search for tactics to reduce the risk of mediated increase in estradiol against the background of such therapy. Alertness occurs when the E2 serum level exceeds the menopause limit by the time the aromatase inhibitors are prescribed. Objective of the study. Determine the tactics for minimizing the risk of increasing estradiol against the background of aromatase inhibitors in combination with GnRH-a in adjuvant therapy for breast cancer in premenopausal patients. Material and methods. 47 patients of ≤ 50 years old with GR + HER2- Stages I-III Breast Cancer and a regular menstrual cycle before the start of neo-/adjuvant chemotherapy were studied. E2 and FSH levels were assessed at the stage prior to chemotherapy and immediately prior to administering adjuvant endocrinotherapy. After the completion of chemotherapy, only 7 out of 47 women had the menstrual cycle - patients without clinical and biochemical suppression of ovarian function (SOF). 86% of cases had cytostatic amenorrhea (n = 40), of which 23 cases (58%) showed that this condition was not combined with the biochemical response of sex hormones, i.e. there was no biochemical SOF. Thus, the study group included 30 patients, who were supposed to be treated with aromatase inhibitors + GnRH analogues, and had no clinical or biochemical menopause by the time adjuvant endocrinotherapy was prescribed. In order to reduce the risk of mediated increase in estradiol, even with pharmaceutical “switching off” ovarian function, the patients were prescribed the GnRH analogue (Buserelin Depot) before starting aromatase inhibitors therapy. Results and conclusion. A progressive decrease in E2 level was determined after each subsequent administration of Buserelin Depot. The median values remained low only after the third injection. Following the chemotherapy, a decrease in estradiol was accompanied by a physiological increase in the FSH levels in 73% of women. The administration of Buserelin Depot led to a significant decrease in FSH median (p <0.01) in 90% of patients. Aromatase inhibitors and continuing GnRH-a were prescribed to 97% of patients. The results indicate that the achievement of ovarian function suppression prior to the administration of IA, can be considered as a reliable tactics for adjuvant endocrinotherapy in patients of reproductive age. The dynamic assessment of reproductive hormones (E2, FSH) is recognized useful when choosing or correcting therapy in such patients.

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