Gonadotropin releasing hormone agonists for the preservation of ovarian function among women with breast cancer who did not use tamoxifen after chemotherapy A systematic review and meta analysis

Capsule:
Resumption of menses 1 year or more after treatment is similar among women with breast cancer who receive a gonadotropin-releasing hormone agonist with chemotherapy or chemotherapy alone.

Authors:
Wendy S. Vitek, M.D., Michelle Shayne, M.D., Kathleen Hoeger, M.D., M.P.H., Yu Han, M.S., Susan Messing, M.S., Chunkit Fung, M.D., M.S.

Volume 102, Issue 3, Pages 808-815

Abstract:

Objective:
To determine whether concurrent use of GnRH agonists with chemotherapy preserves ovarian function in women with breast cancer who did not use tamoxifen.

Design:
Systematic review and meta-analysis.

Setting:
University-based hospitals.

Patient(s):
Premenopausal women with breast cancer treated with chemotherapy who did not receive tamoxifen.

Intervention(s):
Randomization to concurrent GnRH agonists with chemotherapy or chemotherapy alone.

Main Outcome Measure(s):
Odds ratio (OR) of resumption of menses 1 year or more after chemotherapy.

Result(s):
Searches were conducted in PubMed, Scopus, Cochrane Trials Register, and the National Research Register through March 2014, and all randomized trials that reported resumption of menses 1 year or more after GnRH agonist with chemotherapy or chemotherapy alone among women with breast cancer who did not receive tamoxifen were included. Four studies were analyzed in the meta-analysis and included 252 patients (GnRH agonist with chemotherapy, n = 131; chemotherapy alone, n = 121). There was no significant difference in the rate of return of menses between the two groups (OR, 1.47; 95% confidence interval [0.60–3.62]). Heterogeneity among the trials was not significant (I2 = 16.6%).

Conclusion(s):
Concurrent GnRH agonists with chemotherapy may not preserve ovarian function in women with breast cancer. Furthermore, randomized data are limited regarding fertility after concurrent use of GnRH agonists with chemotherapy.

  • Zeev Blumenfeld

    The authors are congratulated for the self criticism. As they correctly claim: “Confirmation of our results will require a prospective trial with a larger number of patients.”
    Indeed, the recently presented results of the NIH sponsored prospective RCT trial [POEMS-SWOG, S0230),on May 30th 2014, at the ASCO annual meeting, had quite different findings. Dr. Halle Moore presented 257 premenopausal breast cancer patients treated by chemotherapy with or without GnRHa. Two years after chemotherapy, only 8% of the GnRHa arm experienced POF vs 22% of control [P<0.05]. In the GnRHa group 21% conceived and 15% delivered, vs only 11% & 7%, respectively, in the controls[P12) evidence supporting the prophylactic use of GnRH-a in women receiving therapy for early unfavorable HL”. They [Behringer et al, 2012] have, therefore, concluded that “the multivariate analysis in the present study reveals that the use of GnRH analogues during therapy is a strong, independent, and a highly significant predictor of pregnancies.” Thus, it seems that the use of GnRH-a cotreatment may preserve not only ovarian function but also fertility. In addition, Clowse et al [2009] have also shown, in their metaanalysis, that among the GnRHa-treated women, the pregnancy rate was significantly higher (RR = 1.65, CI 1.03-2.6). Similarly, Wong et al. [2013], in the largest series of premenopausal breast cancer patients treated with a GnRH-a during chemotherapy reported their outcomes regarding both pregnancy rate and preservation of ovarian function. They, [Wong et al; 2013] have found a high pregnancy rate (71% of the patients who attempted pregnancy achieved it).

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