Adjuvant Endocrine Therapy and Bone Health in Breast Cancer

Abstract

Breast cancer is one of the most common malignancies of women. The majority of breast cancers express estrogen and/or progesterone receptors, permitting anticancer targeting strategies to reduce estrogen signaling in the cancer cells and thereby lowering the risk of breast cancer recurrence. The development of the selective estrogen receptor modulator (SERM) tamoxifen marked a significant milestone in breast cancer care that transcended older estrogen ablative strategies such as oophorectomy and ovarian irradiation. An unintended benefit of tamoxifen in postmenopausal women was bone density preservation. The third generation of aromatase inhibitors (AIs) have demonstrated superior efficacy to tamoxifen in improving disease-free survival in postmenopausal women. However, the AIs significantly increase bone resorption, reduce bone mineral density, and increase the risk of fracture above that of tamoxifen. As a consequence of this, clinical oncologists have assumed a larger role in the screening and treatment of the skeletal complications of breast cancer therapies. The key features of managing bone health in women with early stage breast cancer receiving adjuvant endocrine therapy are reviewed here.

Clinical and translational pharmacology of drugs for the prevention and treatment of bone metastases and cancer‐induced bone loss

“…Chemotherapy is by itself a risk factor for bone loss, independently of subsequent secondary ovarian failure due to chemotherapy. In postmenopausal women, data suggest that patients receiving adjuvant chemotherapy can lose 1–10% of bone mass within 1 year of chemotherapy . Although the World Health Organization (WHO) provides a clinical tool – the Fracture Risk Assessment tool (FRAX) – to evaluate the 10‐year probability of major osteoporotic fractures based on several risk factors, anticancer treatments were not included as a specific risk factor .…”

Effect of Combining Impact-Aerobic and Strength Exercise, and Dietary Habits on Body Composition in Breast Cancer Survivors Treated with Aromatase Inhibitors

“…However, this treatment is associated with musculoskeletal symptoms such as arthralgias, myalgias, osteoporosis-related bone fractures and unfavorable changes in body composition—a reduction of bone mineral density and muscle mass, and an increase in fat tissue and body weight [ 7 ]. Both have been related to poorer survival and an increase in cardiovascular events [ 11 , 12 , 13 , 14 ].…”

Management of Potential Long-Term Toxicities in Breast Cancer Patients

“…Therefore, treatments aimed at inhibiting estrogen signaling in cancer cells are fundamental in patient management. In postmenopausal women, third generation aromatase inhibitors (AIs) have superseded tamoxifen in improving disease-free survival (DFS) at the expense of reduced bone mineral density and increased fracture risk (4), which in turn negatively impacts quality of life(5). Tamoxifen can cause a significant reduction in bone mineral density in premenopausal women, but prevents bone loss in postmenopausal women (6).…”