Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline

Authors: Dhesy-Thind, S. et. al.

Source: J Clin Oncol doi: 10.1200/JCO.2016.70.7257

ascopubs.org/doi/full/10.1200/JCO.2016.70.7257

Bone-modifying agents are medications that prevent the breakdown (resorption) of bone. They are used in postmenopausal women who are at increased risk of fracture due to osteoporosis or from the use of aromatase inhibitors (AI). They are also used in postmenopausal women with breast cancer when there is concern for metastasis.

This panel of experts reviewed the available literature to provide guidelines for use of bone-modifying therapy in breast cancer patients. The work was dedicated to treatment of breast cancer patients who were at risk for metastatic disease. The panel did not evaluate the use of bisphosphonates and other agents to prevent bone loss while on endocrine therapy or due to osteoporosis.

Bisphosphonates resulted in significantly reduced metastasis to bone, fracture rates, breast cancer-specific mortality and improved overall survival. These findings did not vary based upon type of bisphosphonate used, tumor characteristics or use of chemotherapy. Therefore, bisphosphonate therapy should be considered for every postmenopausal woman with breast cancer. This includes younger women who are receiving ovarian suppression. However, it is important to balance each woman’s risk of cancer recurrence against the risk of drug toxicity. Bisphosphonates may hold little benefit for a woman with a low risk of recurrence. For other women, the risks of drug side effects and toxicities may be stronger than the health benefits that they would get from the treatment.

Several bone-modifying agents have been introduced and used in breast cancer patients. However, not all of them have proven benefits in acceptable trials.  Zoledronic acid and clodronate are the only bisphosphonates recommended for adjuvant therapy for breast cancer. Both agents are considered to have similar efficacy. The experts point out that it is beneficial to have more than one agent to offer because patients’ needs are different. Zoledronic acid is given intravenously every six months for 3-5 years, while clodronate comes in a pill that must be taken daily for 2-3 years. The routes of administration and drug side effects and risks allow a provider to choose one medication over the other for individual patients.

Denosumab is not currently recommended for adjuvant therapy. It is frequently used to reduce fracture risk in postmenopausal women with hormone receptor-positive breast cancer on AI therapy. However, there is insufficient data about survival outcomes to recommend it in these guidelines.

The expert panel provided specific guidelines for qualifying a woman as postmenopausal. Time since last menses and specific laboratory values should be considered. Additionally, women should undergo a dental assessment before starting bisphosphonate therapy, as the treatment is associated with a risk of osteonecrosis of the jaw. Finally, serum calcium should be measured prior to beginning treatment and women should take vitamin D and calcium concurrently.