Introduction: In premenopausal women with breast cancer, standard adjuvant endocrine therapy has been 5 years of tamoxifen. This study sought to investigate the safety and feasibility of treating patients who remain premenopausal after adjuvant tamoxifen with gonadotropin-releasing hormone agonist (GnRH-a) concurrent with an aromatase inhibitor, mimicking the strategy that has proven effective in postmenopausal patients.
Patients and methods: This phase II single-arm clinical trial aimed to enroll 50 premenopausal women who had completed > 4.5 years of adjuvant tamoxifen for a 2-year course of leuprolide (7.5 mg intramuscularly monthly or 22.5 mg intramuscularly every 3 months) and letrozole (2.5 mg orally daily). Zoledronic acid (4 mg intravenously every 6 months) was offered optionally to help prevent bone loss.
Results: Despite aggressive recruitment strategies at the 3 participating sites (including Dana-Farber Cancer Institute), poor accrual over 3.5 years ultimately led to early study closure after only 16 patients began therapy. Of the 16, 4 stopped treatment before 1 year, owing to toxicity; 5 completed 2 years of protocol-directed therapy; and 7 remained on treatment as of September 1, 2013, for an average of 53.5 weeks (SD, 17.2 weeks). Hot flashes, vaginal dryness, and pain were common toxicities.
Conclusion: Extended therapy with GnRH-a and an aromatase inhibitor (plus optional bisphosphonate) is associated with substantial side effects in premenopausal women who have already completed > 4.5 years of adjuvant tamoxifen. This study's poor accrual suggests that young women may not be highly motivated to pursue lengthier courses of endocrine therapy and that future studies of this approach may be challenging.
Keywords: Dyspareunia; Endocrine therapy; Hot flashes; Pain; Toxicity.
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