Date of Award


Degree Type

Selective Evidence-Based Medicine Review

Degree Name

Master of Science in Health Sciences - Physician Assistant


Physician Assistant Studies

Department Chair

John Cavanagh, PhD, PA-C


OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the use of intravenous zoledronic acid, in combination with chemotherapy regimens, arrest the development and spread of cancer cells to increase disease-free survival in breast cancer patients.“

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2009 and 2010.

DATA SOURCES: Randomized controlled trials and open label, randomized, phase 2 trial comparing the use of zoledronic acid in combination with chemotherapy to the use of chemotherapy alone were found using Medline/PubMed and Cochrane Databases

OUTCOMES MEASURED: The outcomes measured were incidence of metastasis, progression of disease, and disease-free survival. Mammography, breast ultrasound, MRI, CT scans, and histopathologic studies were used to measure these outcomes after treatment was received.

RESULTS: Two randomized controlled trials and one open label, randomized, phase 2 trial were analyzed in this review. In Aft et al, patients treated with zoledronic acid and chemotherapy had fewer detectable disseminated tumor cells at 3 months than at baseline (p=0.054). In Coleman et al, the residual invasive tumor size after treatment and resection had an adjusted mean difference of 12mm between the two treatment groups (95% CI: 3.5-20.4mm, p= 0.006). Gnant et al demonstrated that the use of zoledronic acid in combination with chemotherapy had a 36% reduction in the risk of disease progression and a 35% reduction in the risk of recurrence compared to chemotherapy alone (p= 0.01 and 0.02, respectively).

CONCLUSION: Based on these three trials, the results of this review were inconclusive. The studies analyzed suggest possible anti-tumor effects leading to increases in disease-free survival. Further research should be aimed at determining a particular chemotherapy plus zoledronic acid regimen and a specific patient population for which zoledronic acid is most effective.