Long term follow up (LTFU) of adjuvant zoledronic acid (ZOL) in high risk early stage breast cancer (ESBC) defined by bone marrow (BM) disseminated tumor cells (DTC).

e12001 Background: BM DTC & peripheral blood CTC indicate metastatic potential. Adjuvant bisphosphonates in postmenopausal patients (pts) result in less bone metastases and better survival. We studied ZOL’s impact on DTC, CTC, and outcomes in ESBC (ASCO, 2010) and now report updated LTFU. Methods: Forty-five pts with ESBC and DTC > 4/mL BM were given ZOL every 4 weeks for 24 months (mo). DTC were quantified at baseline (BL), 12 and 24 mo of ZOL with immunomagnetic enrichment and flow cytometry (Clin Cancer Res, 2015). Serial CTC, survival, recurrence and toxicity were studied. Results: Forty-five pts received ZOL (56% HR+, 18% HER2+, 40% TN, 96% prior chemo). BL median DTC was 13.3/mL (range 4-333). Median DTC decreased from BL to 12 mo (median reduction 6.5/mL, range -57.2 to 23.6) and from BL to 24 mo (median reduction 4.6/mL, range -43.1 to 160.1). For 33 pts with BM at all 3 times, DTC decreased: BL median 11.5/mL (range 4-59.3), 12 mo median 6.8/mL (range 0-28.5), 24 mo median 6.5/mL (range 0.3-168.6). At 12 & 24 mo, 32% & 26% had undetectable DTC respectively. Median CTC was 0.2/mL at BL (n = 45), 0.25/mL at 6 mo (n = 30), 0/mL at 12 mo (n = 22) & 0.2/mL at 24 mo (n = 23). At 123 mo median FU (range 5-154), 9 (20%) pts recurred. Median time to recurrence was 21 mo (range 6-105); 67 % (6/9) TN, 22% (2/9) ER+/HER2+. The first sites of recurrence were CNS in 33% (3), bone & viscera in 22% (2), viscera in 22% (2) and local in 22% (2). BL DTC > 30/mL was associated with higher recurrence (50% > 30 vs. 14% < 30, p = 0.039). All 3 pts with CNS disease had BL DTC > 30/mL. Of the pts who recurred, 4 had ≥ 1 serial BMA; 2/4 had increasing DTC before recurrence. Of 32 disease free pts with BMA at all 3 times, 72% (23) had decreased DTC from BL to 24 mo. Of the 13.3% (6) pts who died, 67% (4) had BL DTC > 30/mL, which was associated with a greater risk of death (50% > 30 vs. 5% < 30, p = 0.006). BL CTC > 0.8/mL was associated with higher recurrence (60% > 0.8 vs. 15% < 0.8, p = 0.047) & death (60% > 0.8 vs. 8% < 0.8, p = 0.013). ZOL was well tolerated. Conclusions: At 123 mo FU, BL DTC > 30/mL and CTC > 0.8/mL correlated with recurrence & death. In this single arm phase II study, adjuvant ZOL decreased DTC over time, supporting the anti-tumor effect of bisphosphonates. Clinical trial information: NCT00295867.