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Breast Cancer

Zoledronic Acid and Survival in Breast Cancer Patients with Bone Metastases and Elevated Markers of Osteoclast Activity

^aMilton S. Hershey Medical Center, Penn State Cancer Institute, Hershey, Pennsylvania, USA; ^bUniversity of Waterloo, Department of Statistics and Actuarial Science, Waterloo, Canada; ^cJuravinski Cancer Centre, Hamilton, Canada; ^dMassachusetts General Hospital Cancer Center, Boston, Massachusetts, USA; ^eUniversity of Sheffield, Weston Park Hospital, Cancer Research Centre, Sheffield, United Kingdom

Key Words. Biologic markers • Breast neoplasms • Survival rate • Zoledronic acid

Correspondence: Allan Lipton, M.D., Milton S. Hershey Medical Center, Penn State Cancer Institute, 500 University Drive, Hershey, Pennsylvania 17033, USA. Telephone: 717-531-5960; Fax: 717-531-5076; e-mail: alipton{at}psu.edu

Disclosure: R.J.C. has acted as a consultant to and performed contract work for Novartis Pharmaceuticals Corporation.P.M. has acted as a consultant to Novartis Oncology. M.R.S. has acted as a consultant to and has a financial interest in Novartis Oncology. R.E.C. has acted as a consultant to and has a financial interest in Novartis. A.L. has acted as a consultant to Novartis, Merck, Amgen, and GlaxoSmithKline, and he has a financial interest in Novartis, Amgen, and Pfizer.

Objective. Most breast cancer patients with bone metastases will receive bisphosphonate treatment. This post hoc analysis investigated whether early normalization of urinary N-telopeptide of type I collagen (NTX) levels during bisphosphonate therapy correlates with a long-term reduction in skeletal-related event (SRE) risk and mortality in patients with breast cancer.

Methods. This was a retrospective subset analysis of a phase III randomized trial comparing i.v. zoledronic acid with pamidronate treatment in patients with bone metastases from breast cancer or multiple myeloma. Patients with breast cancer who had NTX assessments at baseline and at months 1 and 3 (n = 342) were classified as normal (NTX <64 nmol/mmol creatinine) or elevated (NTX 64 nmol/mmol creatinine). The relative risk for an SRE or death was estimated with Cox regression models.

Results. Among the 328 evaluable patients treated with zoledronic acid, 196 patients (59.7%) had elevated baseline NTX, with 149 of those patients (76.0%) having normalized NTX levels and 31 patients (15.8%) having persistently elevated NTX levels at 3 months. The normalized NTX group had significantly lower risks for a first SRE, a first fracture or surgery to bone, or death than the group that had persistently elevated NTX levels.

Conclusions. These results suggest that early normalization of elevated baseline NTX while receiving zoledronic acid is associated with longer event-free and overall survival times compared with persistently elevated NTX. Further analyses in cancer patients with elevated marker levels are warranted to confirm the implications of these findings.

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