Zoledronic acid provides long-term benefit in premenopausal estrogen receptor positive breast cancer patients
At the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, researchers demonstrated the continued effectiveness of treating patients with estrogen receptor-positive (ER+) breast cancer with adjuvant zoledronic acid in combination with adjuvant endocrine treatment. Updated data from the ABCSG-12 study confirmed and extended the results reported at 48 and 62 months of follow-up. Now at 84 months of follow-up, patients are experiencing drastically fewer recurrences of breast cancer and improved rates of survivorship without toxic side effects.
In the phase III ABCSG-12 trial, 1,803 premenopausal patients with early-stage, ER+ breast cancer treated with goserelin were randomly assigned to tamoxifen or anastrozole or each of these two treatments in combination with zoledronic acid for three years. In the initial report, presented in 2008, professor Gnant (Medical University of Vienna, Austria) reported significantly improved disease-free survival. The presented long-term data at 84 months of follow-up revealed a 28% reduction in the risk of recurrence (HR[95%CI]: 0.72[0.56-0.94]; p= 0.014). This finding is in line with the results presented at 48 (HR:0.74), 62 (HR:0.68) and 76 (HR:0.73) months of follow-up. Furthermore, the long-term data revealed a 36% reduction in the risk of death among patients treated with zoledronic acid. The overall survival in the ABCSG-12 study was excellent with 95.5% of the patients still alive after 7 years of follow-up. Moreover, no patients in the study experienced osteonecrosis of the jaw or renal failure, proving the safety of the treatment seven years later.
Interestingly, Gnant showed that patients older than 40 years of age with a presumed complete ovarian blockage experienced a more pronounced effect than younger patients. Patients older than 40 had a 34% reduced risk of recurrence and a 44% reduced risk of dying. For patients younger than 40 on the other hand, no significant survival benefit was seen (HR[95%CI]: 0.87[0.55-1.36]; p=0.525).
“The anticancer effects of adjuvant zoledronic acid are now well established in endocrine-responsive patients,” said professor Gnant. “Zoledronic acid was shown to be safe and well tolerated in several phase III studies with over 7,000 patients in total. Furthermore, ABCSG-12, ZO-FAST and the postmenopausal subgroup of the AZURE study demonstrated significant survival benefits for adjuvant zoledronic acid.” All these data suggest that adding zoledronic acid to adjuvant endocrine therapy including ovarian function suppression should be considered for premenopausal women with ER-positive early breast cancer.