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Breast cancer is the second most common cause of death in all cancer female patients in USA; it is estimated that 234.580 new cases of invasive breast cancer will be diagnosed among women, of which approximately 40,030 women were expected to die from it in the year 2013.
Adjuvant hormonal treatment remains an integral component in the treatment of early breast cancer (EBC). Tamoxifen was the drug of choice for more than 30 years, as it significantly reduced recurrence and breast cancer-related mortality.
Evidence has emerged over the past decade to suggest that hormonal therapy with the aromatase inhibitors (AIs) anastrozole, letrozole and exemestane offers some significant efficacy and/or safety benefits over tamoxifen.
Menopause-related decreases in estrogen have been associated with an increased loss of bone mineral density (BMD), osteoporosis and increased fracture risk, and the profound reduction in plasma estrogens in postmenopausal women receiving AI therapy for EBC can further increase this risk.It is now evident that, in addition to decreased BMD, clinical risk factors can greatly influence fracture risk. In addition to morbidity and mortality, fractures are associated with high health care costs and increased health care utilization for several months after fracture incidence. Typically, hip and vertebral fractures are associated with prolonged disability and lack of autonomy, thereby leading to increased indirect costs. Improvements in assessing fracture risk can help identify patients who need pharmacologic intervention to improve bone health, which could help reduction of fracture incidence. An evidence-based algorithm is presented for assessing bone health and initiating antiresorptive therapy in postmenopausal women initiating AI therapy for early-stage breast cancer.
Although the trials of adjuvant ZOL were not powered to detect significant differences in fracture rates between groups additional follow-up may provide more insight regarding the effects of treatment on long-term fracture incidence.
In addition to the established risk factors used in bone health algorithm, other potential fracture risk factors in women with breast cancer include low weight and family history of non-hip fractures. An additional potential risk factor is excessive alcohol consumption (which is not the case in our society).
Overall, data from the AIBL studies setting as well as long-term duration to treat postmenopausal osteoporosis strongly recommend that bisphosphonates are safe and effective agents for preserving bone health during adjuvant endocrine therapy for breast cancer.
Moreover, emerging anticancer benefits (e.g. reduced disease recurrence, improved disease-free survival, and prolonged overall survival) due to the use of bisphosphonates provide additional reasons to proactively use these agents during adjuvant AI treatment. Ongoing trials are evaluating the potential of oral and i.v. bisphosphonates and denosumab to prevent breast cancer recurrence. As data from these trials mature, the role of antiresorptive agents in EBC is likely to evolve.