Zhang Y, et al. - Researchers performed this study to examine ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. Findings revealed that the sequential use of GnRHa and chemotherapy resulted in the ovarian preservation and survival outcomes that were no worse than simultaneous use. Until menstruation resumption after chemotherapy, the application of GnRHa could probably be delayed.

Methods

• Researchers performed a phase 3, open-label, parallel, randomized controlled trial (NCT01712893) enrolling 216 premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer from July 2009 to May 2013.
• They randomized the patients at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment.
• For at least 2 years, GnRHa treatment was advised to all patients.
• The incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels constituted the primary outcome measure.
• The secondary endpoints were the menstrual resumption period and survivals.

Results

• Researchers followed-up the patients for a median period of 56.9 months (IQR 49.5–72.4 months).
• Each group comprised of 108 patients.
• In the sequential and simultaneous groups, complete primary endpoint data of 92/108 and 78/108 patients was available.
• The rates of early menopause were 22.8% (21/92) and 23.1% (18/78) in the sequential and simultaneous groups, respectively [simultaneous vs. sequential: OR 1.01 (95% CI 0.50–2.08); p=0.969; age-adjusted OR 1.13; (95% CI 0.54–2.37); p=0.737].
• For the two groups, the median menstruation resumption period was 12.0 (95% CI 9.3–14.7) months and 10.3 (95% CI 8.2–12.4) months [HR 0.83 (95% CI 0.59–1.16); p=0.274; age-adjusted HR 0.90 (95%CI 0.64–1.27); p=0.567].
• The groups were not significantly different in terms of disease-free survival (p=0.290) or overall survival (p=0.514).