Drugs that Increase BMD Important for Bone Health in Breast Cancer

Bone health is increasingly recognized as an important factor in women with breast cancer, with adverse effects possible from both cancer and its treatment.

At the recent meeting of the American Society of Clinical Oncology, Larry J. Suva, PhD, of the University of Arkansas for Medical Sciences, Little Rock, noted that 2 major bonerelated processes are of concern in early-stage breast cancer: postmenopausal-and treatment-induced osteoporosis, and the development of bone metastases in any patient with breast cancer.

Patients with breast cancer often have osteoporosis. Osteoporosis oc curs when bone remodeling favors the resorption process mediated by osteoclasts, which are stimulated by the receptor activator of the nuclear factor kappa-beta ligand (RANKL). During bone resorption, activated osteoclasts produce molecules and enzymes that can degrade the bone matrix. Agents that inhibit osteoclast activity, therefore, can promote bone health, according to Dr Suva.

In patients with breast cancer who have osteoporosis, recent data are showing that bisphosphonates, as well as denosumab, which is currently under FDA review, can increase bone mineral density (BMD). Bisphosphonates inhibit an important enzyme in osteoclasts while denosumab inhibits RANKL, he explained.

Osteoclastic activity may also be important in the metastatic process. Interleukin-8 (IL-8) is an inflammatory marker common in postmeno pausal women with osteoporosis and in women with breast cancer. IL-8 is implicated in bone resorption, and high levels of IL-8 have been correlated with decreased survival in patients with metastatic breast cancer.

Agents that inhibit osteoclast activity are now recognized for their protective role in breast cancer, Dr Suva noted. A recent pivotal study (N Engl J Med. 2009;360:679-691) showed that the addition of the bisphosphonate zoledronic acid to adjuvant endocrine therapy in patients with early-stage breast cancer reduced the risk of disease progression by 36%. “Patients with early-stage disease can have better clinical outcomes if treatment regimens also incorporate agents that inhibit osteoclast activity,” said Michael Gnant, MD, Medical University of Vienna, Austria, during this bone biology session at ASCO.

Bone loss associated with aromatase inhibitors is a rising concern, said Catherine H. Van Poznak, MD, of the University of Michigan, Ann Arbor. In managing breast cancer, clinicians should address such comorbid factors and concerns as osteoporosis, and should balance the risk:benefit ratio of specific treatment options.

Oral bisphosphonates, which are indicated for the prevention/treatment of osteoporosis, can substantially in crease BMD in patients with bone loss associated with aromatase in hibitors in postmenopausal women, said Dr Van Poznak, and potentially also in premenopausal patients, and in women with breast cancer and chemotherapyinduced ovarian failure, she said.

Henry G. Bone, MD, of the Michi gan Bone and Mineral Clinic, stressed the importance of calcium and vitamin D in patients with breast cancer, and emphasized the value of oral bisphosphonates as a means of preventing bone loss associated with aromatase inhibitors.

“Strictly from the standpoint of preventing or treating osteoporosis, conventional dosages of bisphosphonates should be adequate in women receiving adjuvant therapy,” Dr Bone said, but he noted that studies evaluating bisphosphonates in conjunction with aromatase inhibitors used much higher doses than those used in postmenopausal women with osteoporosis. The “limiting dose” of these agents in the breast cancer setting is not yet clear