[The role of bisphosphonates of adjuvant therapy in breast cancer]

Abstract

Breast cancer is the most common neoplasm in women. Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. Biphosphonates, antiosteolytic agents, have been shown to reduce the progression of established bone metastases. Emerging evidence suggests that biphosphonates also have antitumor and antimetastatic properties, including the inhibition of angiogenesis, tumor-cell invasion, and adhesion in bone; the induction of apoptosis; antitumor sinergy with cytotoxic chemotherapy; and immunomodulatory effects through induction of γ/δ T cells. These findings were the background and rationale for ongoing clinical trials, in order to establish their role as a part of adjuvant treatment for early breast cancer. The oral biphosphonate clodronate (1600mg/d) is effective in patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for two years, clodronate has been reported to reduce the risk of bone metastases during a 2-year study period with a significant reduction in mortality. This benefit supports its use as additional adjuvant therapy for patients with operable breast cancer. Zoledronic acid, a potent nitrogen-containing biphosphonate, has been shown to maintain or increase bone mineral density (BMD) in premenopausal women with early-stage breast cancer receiving adjuvant hormone therapies as well as healthy postmenopausal women with low BMD. Recent large clinical trials with biphosphonates in the (neo)adjuvant setting for early-breast cancer, demonstrate an improvement of disease-free and overall survival as well as increased pathologic rate responses.