17 July, 2017:
Several guidelines have been reported for bone-directed treatment in women with early breast cancer for averting fractures, particularly during aromatase inhibitor (AI) therapy. A systematic literature review identified both several fracture-related risk factors as well as recent advances in the management of aromatase inhibitor-associated bone loss (AIBL). Although the FRAX algorithm includes fracture risk factors in addition to bone mineral density (BMD), it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women, with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL.
A Joint Position Statement of the International Osteoporosis Foundation, the Cancer and Bone Society, the European Calcified Tissue Society, the International Expert Group for AIBL, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, the International Society for Geriatric Oncology and the International Menopause Society recently provided a treatment algorithm . In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score <−2.0 or with a T-score of < –1.5 SD with one additional risk factor, or with two or more risk factors (without BMD) for the duration of AI treatment. Patients with a T-score > −1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12–24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer-specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.
The use of adjuvant endocrine therapy in women with hormone-sensitive breast cancer is divided, usually by menopausal status, between the selective estrogen receptor modulator tamoxifen and the newer class of drugs known as aromatase inhibitors. The latter are indicated in postmenopausal women only. A Cochrane systematic review  found that disease-free survival and overall survival were improved with AI monotherapy compared to tamoxifen. Sequenced therapy with AI to tamoxifen (or vice versa) improved disease-free survival compared to tamoxifen but not overall survival. Fractures were more frequently associated with AI use. Thromboembolic disease and endometrial cancer were more frequently associated with tamoxifen use. AIs have largely replaced tamoxifen in adjuvant treatment of postmenopausal hormone receptor-positive breast cancers.