Abstract P6-14-04: Effect of Zoledronic Acid on Disease-Free Survival and Overall Survival in Women with Clinic Stage II/III Undergoing Neoadjuvant Chemotherapy for Breast Cancer
Authors: Aft R , Naughton M , Trinkaus K , Weilbaecher K. 
Published: April 2011

Abstract
Background: We conducted a randomized Phase II study examining the effect zoledronic acid (ZA) on disseminated tumor cells (DTC) in women undergoing neoadjuvant chemotherapy (Lancet Oncology11:421). We now report on the effect of ZA administered concurrently with neoadjuvant/adjuvant chemotherapy on disease-free survival and overall survival in this patient population.
Methods: Between March 2003-2006, 120 women with newly diagnosed clinical stage II/III breast cancer were randomized to either ZA 4 mg IV every 3 weeks for 1 year starting with the first cycle of chemotherapy or no bisphosphonate. 4 cycles of epirubicin (75 mg/m2)/docetaxel (75 mg/m2) were given prior to surgery and 2 cycles in the adjuvant setting. Eligible patients received adjuvant endocrine therapy and trastuzumab. Disease-free survival was defined as the time from trial registration to first detectable recurrence. Overall survival was defined as the time from trial registration to date of breast-cancer related death. Data was analyzed using Kaplan-Meier and Cox proportional hazard models.
Results: Of 120 patients randomized 119 patients were evaluable. Treatment arms were balanced for grade, menopausal status, and tumor biomarkers. Tumors of 55 (46.2%) women were estrogen-receptor (ER) positive/Her2-negative, 40 (33.6%) were ER-negative/Her2-negative and 24 (20.2%) were Her2-positive.With a median follow up of 61.9 (4.93-85.43) months, there was no significant difference in recurrence or survival between the ZA and no ZA groups (p=0.88, p=.92 respectively). Subgroup analysis demonstrated that time to recurrence and death was significantly different between patient groups based on ER-status and ZA treatment (p=.013 for recurrence, p=.013 for survival).
Months
Time to recurrence and hazard of death was similar in three of the subgroups, ER-positive/Her2-negative/control, ER-positive/Her2-negative/ZA, and ER-negative/Her2-negative/ZA (p&gt;.05 for recurrence and p&gt;.05 for survival. ER-negative/Her2- negative patients in the no ZA treatment arm experienced a significantly decreased time to recurrence and survival compared to ER-positive patients (p=.0039, p=.0074, respectively). The hazard ratio of death for ER-negative/Her2-negative patients was reduced from 8.36 to 3.15 with ZA treatment. The estimated 5yr survival for ER-positive/Her2-negative/control, ER-positive/Her2-negative/ZA, ER-negative/Her2-negative/control, ER-negative/Her2-negative/ZA were 96.6%, 80.0%, 63.2% and 81.0% respectively.
Discussion: ZA administered with chemotherapy conferred a disease-free survival and overall survival benefit to a subset of breast cancer patients with ER-negative/Her2-negative tumors. Longer follow-up may be required to determine if there is a benefit in other tumor subgroups. Larger studies are warranted to examine the effects of ZA in patients at high risk of developing metastatic disease.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-04.