Dr. Gralow on Breast Cancer Adjuvant Bisphosphonates

Julie R. Gralow, MD, Director, Breast Medical Oncology, Seattle Cancer Care Alliance, elaborates the mixed results seen in multiple trials that studied the use of adjuvant bisphosphonates to prevent bone loss or metastases for women with breast cancer.

Positive data is available showing that up to 5 years of bisphosphonates could improve the risk for recurrence and help prevent bone loss.

The Austrian ABCSG-12 trial in premenopausal patients receiving endocrine therapy with ovarian suppression added 6 doses of zoledronic acid over the course of 3 years. The trial found an increase in disease-free survival and demonstrated an improvement in overall survival. Additionally, the ZO-FAST trial found a reduction in aromatase inhibitor induced bone loss with the introduction of zoledronic acid every 6 months for postmenopausal women with breast cancer.

In addition to the positive results for adjuvant bisphosphonates, negative findings have also been prevalent.

The most prominent negative trial was AZURE, which led the manufacturers of zoledronic acid to withdraw their application for breast cancer risk reduction. Gralow notes that women on this trial were both pre- and postmenopausal and most had received chemotherapy, which may have contributed to the lack of results. Other adjuvant bisphosphonate trials, such as those looking at clodronate, showed similar mixed results to those examining zoledronic acid.

An examination of these results shows a benefit for adding bisphosphonates in the adjuvant setting, but only when there is low chemotherapy use, the tumors are largely estrogen receptor-positive, and the women have an induced or spontaneous menopausal state. Patients that meet these criteria seem to experience the most benefit from the introduction of bisphosphonates in the adjuvant setting.

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