Reduction in New Metastases in Breast Cancer with Adjuvant Clodronate Treatment

Reviewers: John Han-Chih Chang, MD and Kenneth Blank, MD
Source: New England Journal of Medicine, 339 (6):357

Introduction

Bisphosphonates are a class of drugs that are increasingly being used totreat osteoporosis. These medications inhibit the function of the cellthat functions normally to destroy bone- the osteoclast. In 1996 a studypublished in the New England Journal of Medicine found that pamidronate-a bisphosphonate- reduced skeletal complications (fractures, bone painetc.) in women with breast cancer, and later that year the FDA approved pamidronate for use in this patient population, as well as in patientswith myeloma (a form of bone cancer).

Materials and Methods

A study published in the August 6, 1998 New England Journal of Medicinelooked at the effect of clodronate- a bisphosphonate- on the incidenceof metastasis in patients with breast cancer. The study limitedenrollment to patients who were shown to have cancer cells in their bonemarrow, and hence at high risk for developing bone metastasis. Thepatients were randomized to receive clodronate (1600mg per day, orallyfor two years) or nothing. Enrollment began in 1990 and closed 5 yearslater when 302 patients had agreed to participate. The median follow uptime was 36 months. Patients were treated for their breast cancer withstandard treatment including surgery, radiotherapy and chemotherapy.

Results

The mean number of bone metastasis was significantly reduced in thegroup of patients receiving clodronate: 3.1 versus 6.1. In addition, thenumber of visceral metastasis (metastasis in body organs such as theliver and lung) was lower, and the number of patients who died was alsolower (6 versus 22).

Discussion and Conclusions

The authors conclude that clodronate can reduce theincidence of new bony and visceral metastasis in high-risk breast cancerpatients. As with all studies, many questions remain willbisphosphonates prove effective in the majority of breast cancerpatients who do not have bone marrow involvement? And, are allbisphosphonates alike- or are some more effective than others? Finally,the follow-up was short- 3 years- and only with longer follow-up will itbe clear whether the clodronate actually prevents the formation if bonymetastasis or simply delays their appearance.