Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance

Abstract

Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables.

Keywords: aromatase inhibitors; breast cancer; musculoskeletal toxicity.

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

Figures

Figure 1.

Treatment with vitamin D supplements (0.266 mg/16,000 IU) if baseline 25-hydroxyvitamin D is less than 30 ng/ml. BP, bisphosphonate; FxOP, osteoporotic fracture; OP, osteoporosis; RF, fracture risk.

Figure 2.

Vitamin D level at baseline.

Figure 3.

Baseline BMD according to WHO (’94) criteria.

Figure 4.

Relationship between vitamin D levels at 3 months and BMD loss at 1 year.