91IN - Osteoarticular toxicity

Date 27 September 2014
Event ESMO 2014
Session Targeting precision medicine toxicity
Topics Complications of Treatment
Supportive Care
Presenter Ignasi Tusquets
Citation Annals of Oncology (2014) 25 (suppl_4): iv33-iv34. 10.1093/annonc/mdu310
Authors I. Tusquets
  • Medical Oncology, Hospital del Mar, 08034 - Barcelona/ES




Several antineoplasic drugs could have a negative impact on bone health. Androgen deprivation therapy is a classical example in prostate cancer cases, and aromatase inhibitors (AI) are probably the most paradigmatic group of drugs with potential skeletal adverse events in breast cancer. AI are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AI have an increased risk of bone loss and arthralgias compared with those treated with tamoxifen. The mechanism for the accelerated bone loss is thought to be, at least in part, profound suppression of estrogens synthesis; the end result is increased osteoclast activation and net bone resorption. In addition to the effects of AI, the population of women with early breast cancer has a high prevalence of vitamin D insufficiency. In our specific experience (Nogues X, et al. Maturitas 2010. Servitja S, et al. The Breast 2012), 88% of the patients had concentrations <30 ng/ml (defined as vitamin D deficiency). The implementation of individualized vitamin D supplementation achieved normal levels in half of our patients in less than 3 months, and those patients who achieved concentrations >30 ng/ml experienced significantly less bone loss than those women who don't reach 25OHD normal concentrations (Servitja S, et al. ASCO 2011). Another relevant finding in our research program was the description of a close relationship between 25OHD levels and intensity of aromatase inhibitors-related arthralgias (AIrA). A target concentration of 40 ng/ml 25OHD may prevent development of AIrA but higher loading doses are required to attain this level in women with deficiency at baseline (Prieto-Alhambra D, et al. Breast Cancer Res Treat 2011). We also demonstrate that AIrA is genetically determined: SNPs 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 (Garcia-Giralt N, et al. Breast Cancer Res Treat 2013). The determination of these SNPs could be useful in clinical practice to identify women at high risk of AIrA and therapy discontinuation, who could then be targeted for higher dose vitamin D supplementation and/or monitoring strategies to improve quality of life and compliance.


The author has declared no conflicts of interest.