The majority of breast malignancies are hormone responsive a
The majority of breast malignancies are hormone responsive, and adjuvant endocrine therapy is used routinely to prevent breast cancer recurrence and death [6,7]. Tamoxifen was the past treatment of choice for endocrine-responsive postmenopausal breast cancer and was found to preserve BMD in postmenopausal (but not premenopausal) women , and fracture risks remained similar in postmenopausal tamoxifen users and non-users . However, aromatase inhibitors (AI) have now replaced tamoxifen as the treatment of choice for hormone-responsive breast cancer in most postmenopausal women because of both better efficacy and fewer serious side effects such as induction of uterine cancers and thromboembolic events.[6,7,10,11] However, because AIs prevent peripheral KC7F2 weight production, they suppress estrogen levels beyond that attained from a natural menopause, thereby leading to accelerated bone loss and an increased fracture risk [12–15].
Besides a reduction in quality of life, increased morbidity and treatment induced fractures lead to an increase in the health economic burden. A recent study reported that compared to the general population, breast cancer patients had fracture incidence rate ratios of 1.25 (95% CI: 1.23–1.28) and 1.18 (95% CI: 1.14–1.22) for hospitalization due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Women taking aromatase inhibitors were at an increased risk of fracture as compared with women taking tamoxifen (HR 1.48; 95% CI: 0.98–2.22). Additionally, breast cancer patients hospitalized for a bone fracture showed a higher risk of death (HR 1.83; 95% CI: 1.50–2.22) compared with those without bone fracture .
Identification of fracture risk in women with breast cancer Several additional clinical risk factors have been validated in large, prospective, population-based studies in postmenopausal women and were previously characterized according to their impact on overall fracture risk independently of both age and BMD (Evidence level IA) . Risk factors found to increase fracture risk in women with breast cancer in addition to AI therapy included, T-score <–1.5, age >65 years, low BMI (<20kg/m2), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, rheumatoid arthritis, and smoking [73–79] (Evidence level IA). Additionally, a recent study suggests that cancer associated muscle weakness leads to increased immobility with an increased risk for osteoporosis and fracture . Recent data suggest that BMD measurement alone should not be the sole criterion for determining fracture risk, and that an overall fracture risk assessment that combines risk factors provides a more accurate evaluation. It is also important to note that the use of corticosteroids at a dose of >2.5mg prednisolone (or equivalent) daily for more than 3 months is an established risk factor based on data from non-malignant disease settings. When combined with chemotherapy regimens, the doses of oral corticosteroids are typically higher, and might negatively impact bone health over a shorter period of time. Finally, in order to identify and manage secondary causes of osteoporosis, complete baseline laboratory assessments should include serum levels of calcium, phosphate, 25-OH vitamin D, C-reactive protein, alkaline phosphatase, thyroid-stimulating hormone, and gamma-glutamyl transpeptidase; complete blood count; creatinine clearance; and protein electrophoresis (serum and/or urine).
Selecting a treatment to prevent AIBL Available data from randomized clinical trials in more than 6000 patients suggest that denosumab, intravenous and oral bisphosphonates can effectively prevent AIBL in patients with breast cancer (Table 2) [69,81–90]. Although the majority of these trials were not designed with a fracture prevention endpoint, data from the osteoporosis setting support the use of BMD improvements as a surrogate for fracture prevention . Therefore, data from these large RCTs may be considered level II evidence for preserving skeletal health during AI therapy.