J. Clin. Oncol. 2018-07-01
Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data.
Abstract
Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
Related Questions
In which situations do you offer ovarian suppression with chemotherapy to prevent the development of premature menopause in premenopausal women with ER negative breast cancer?
I would consider the use of GnRHa during chemotherapy in all women that are premenopausal at breast cancer diagnosis (irrespective of age) and that are concerned about developing the side effects of early menopause. Current evidence supports its use as a standard strategy for ovarian function preser...
Is there a subset of breast cancer patients who may benefit more from GnRH analogs for fertility preservation compared to others?
In the prior research and the meta-analysis conducted by Lambertini et al., use of GnRH was not associated with any group of premenopausal women doing worse from a disease standpoint. Further we now know from the Suppression of Ovarian Function with Triptorelin Trial (SOFT) that adding ovarian suppr...
For women who have had either embryo or oocyte cryopreservation, do you also recommend administering GnRH analogs?
For anyone who is interested in fertility preservation enough to undergo egg or embryo cryopreservation, I think offering GnRH analog treatment through chemotherapy for prevention of premature ovarian insufficiency and potentially infertility makes sense. Although some women may not want to deal eve...
How do you approach and counsel women with high risk, early stage breast cancer requiring chemotherapy for whom fertility preservation is a major concern?
Fertility preservation is a major issue in survivorship for younger cancer patients. Discussion with a specialist regarding banking eggs or embryos as early as possible is important. Proven techniques such as embryo cryopreservation may not be available due to financial constraints or other issues. ...