GnRHa protects ovarian function during chemotherapy for breast cancer
medwireNews: Adding a gonadotropin-releasing hormone analog (GnRHa) to cyclophosphamide-containing chemotherapy significantly reduces the risk for premature ovarian insufficiency (POI) in premenopausal women with breast cancer, Chinese research shows.
Based on their analysis, Xiangyun Zong (Shanghai Jiao Tong University Affiliated Shanghai Sixth People’s Hospital) and co-investigators say: “Gonadotropin-releasing hormone analogs should be used to protect ovarian function in premenopausal women who are receiving chemotherapy for breast cancer.”
The study included 330 premenopausal women (median age 41 years) who were randomly assigned to receive cyclophosphamide-containing chemotherapy with (n=165) or without (n=165) a GnRHa. Those in the GnRHa group were given subcutaneous goserelin 3.60 mg or leuprorelin 3.75 mg every 28 days from 1 to 2 weeks before the first chemotherapy cycle until 4 weeks after the last cycle.
After excluding 29 patients with POI (anti-Müllerian hormone [AMH] levels < 0.5 ng/mL) at baseline, the researchers found that women given a GnRHa had a significant 77% lower risk for POI at 12 months than those who did not receive GnRHa treatment.
Specifically, the POI rates at 12 months were 10.3% of 146 participants in the GnRHa group and 44.5% of 155 in the control group.
In addition, AMH resumption, where levels increased to above the 0.5 ng/mL cutoff after chemotherapy, was a significant 4.4 times more likely to occur with versus without GnRHa, at rates of 60.0% versus 13.6% among the 25 and 44 patients with available data, respectively.
Writing in JAMA Oncology, Zong and co-authors note that “[i]n this study, all chemotherapy-induced POI occurred in patients older than 35 years, suggesting that patients older than 35 years are the risk group for ovarian function injury that is caused by chemotherapy.”
After a median 49 months of follow-up, the researchers found no significant difference in 4-year overall survival (OS) rates between the people who did and did not receive a GnRHa (96 vs 97%). There was also no difference in the 4-year tumor-free survival (TFS) rates (85% in both groups).
They did, however, note that both outcomes were significantly better with versus without a GnRHa in the subgroup of 54 patients who were younger than 35 years at baseline. In this group, the 4-year OS rate was 100% in the women who were given a GnRHa compared with 81% in the women who were not. The corresponding 4-year TFS rates were 93% and 62%.
Zong et al say that although “fertility is a major concern” among young women with breast cancer, up to now “there has been no prospective randomized clinical study on ovarian function related to breast cancer in Chinese or Asian populations.”
They conclude that their study shows that “female patients with breast cancer in the Chinese population who were receiving chemotherapy could also benefit from applying GnRHa and GnRHa could be recommended as an option to protect ovarian function during treatment with chemotherapy.”
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