Aromatase Inhibitor-associated Bone Loss in Breast Cancer

Abstract

In 2006, breast cancer was the most commonly diagnosed cancer among women, comprising approximately 31% of new cancer cases, and resulting in 15% of all cancer-related deaths in the US. 1 In a large proportion of the newly diagnosed breast cancer cases, breast cancer tumors are hormone-responsive; therefore, estrogen and its receptor have become the targets of choice for therapeutic intervention. Estrogen suppression prevents or reduces growth of estrogen receptor-positive (ER+) tumors, and can be achieved through surgical or targeted therapeutic modalities. Early surgical and radiological ovarian ablation strategies have given way to more targeted therapies involving the detection of ER status and compounds such as tamoxifen that block tumor-cell growth at the ER level. Tamoxifen was the therapy of choice for hormone-responsive breast cancer and is still commonly prescribed. However, many patients still experience disease recurrence despite ongoing tamoxifen therapy. Furthermore, tamoxifen is associated with serious adverse events, most notably thromboembolism (blood clots) and endometrial cancer, and therapy is limited to five years. Therefore, alternative approaches with improved efficacy to target ER+ breast cancer tumors have been developed. Aromatase inhibitors (AIs) block estrogen production in the peripheral tissues by preventing the last step in estrogen biosynthesis. The superior efficacy and more favorable side-effect profile demonstrated by AIs have allowed them to begin to replace tamoxifen as the adjuvant therapy of choice for post-menopausal women with ER+ breast cancer. 2‐5 However, one caveat of AI therapy is accelerated bone loss and increased fracture risk in a population of women that may already be at risk for fracture related to chemotherapy, low bone mineral density (BMD), age, history of fragility fracture after the age of 50, family history of hip fracture, or treatment history. 4‐8 The goal of adjuvant hormonal therapy for early breast cancer is to prevent local or distant disease recurrence or prolong disease-free survival (DFS) or overall survival (OS). Recent head-to-head clinical trials demonstrate that AI treatment is superior to tamoxifen for achieving this goal. To this end, maximum clinical benefit may be achieved by combining AI therapy with bisphosphonates in patients at risk for fracture to ensure optimal breast cancer management and prevent bone loss. 9,10 This review briefly summarizes the available data regarding aromatase inhibitor-associated bone loss (AIBL) and provides insight into ongoing trials for the prevention of AIBL with bisphosphonates.