The Use of Bisphosphonates in Patients With Breast Cancer

Catherine H. Van Poznak, MD


Cancer Control. 2002;9(6) 

In This Article

Risk of Bone Metastases and Skeletal Complications of Malignancy

Studies to identify risk factors associated with relapse in bone have been performed. Colleoni et al[4] evaluated breast cancer patients from the International Breast Cancer Study Group, adjuvant trials I through VII, for pattern of recurrence among 6,792 patients. The cumulative incidence of bone metastases was highest among patients with more than four axillary lymph nodes involved, tumor size greater than 2 cm, estrogen receptor-positive tumors, and age less than 35 years at diagnosis. Similarly, Smith et al[5] reported their assessment of 14,614 women from seven National Surgical Adjuvant Breast and Bowel Project (NSABP) trials where involved axillary lymph nodes and estrogen receptor positivity correlated with subsequent development of bone recurrence. In a smaller study, Solomayer et al[6] reported a retrospective analysis of 648 patients with metastatic breast cancer. Bone as the first metastatic lesion correlated with positive estrogen and progesterone receptor status, tumor grade, and S-phase fraction, but not tumor size, nodal status, or menopausal status.

Domchek et al[3] evaluated the incidence rate of bone complications and sought to identify predictors of skeletal complications in 718 patients who had developed metastatic breast cancer between 1981-1991, a time period that predated the use of bisphosphonates. This study demonstrated that approximately 50% of patients developed bone complications (hypercalcemia, spinal cord compression, surgical intervention to bone, radiation therapy to bone, or pathologic fracture). Predictors of skeletal complications included bone involvement at the time of diagnosis of metastatic disease, abnormal alkaline phosphatase, and a disease-free interval of less than 3 years since primary therapy.

Methods of reducing the impact of breast cancer are actively being sought, and paramount in this effort is the identification of patients at increased risk of visceral and/or skeletal metastases. Active investigation is underway to help define prognostic factors beyond tumor size, hormonal receptor status, and conventional analysis of lymph node status. At present, the importance of cytokeratin positive lymph nodes and bone marrow are being investigated; it is anticipated that these findings will impact treatment decisions for adjuvant therapy.[7] Breast cancer cells have been found in the circulation of patients, but the significance of this has yet to be realized.[8] Research is ongoing to identify new prognostic and predictive factors.


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