Abstract
Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor-positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. This work aimed to assess bone loss, fracture incidence, and risk factors associated with these events, as well as the prognostic influence of fractures. We have conducted a retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. Four-hundred-and-fifty-one eligible women were reviewed (median age 68 years). Median time under AI was 40 months. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in older women (mean 74 vs. 68 years, p = 0.006). Age (OR 1.01, 95% CI 1.01–1.07, p = 0.024) and time under AI (OR 1.02, 95% CI 1.00–1.04, p = 0.037) were independent predictors of fracture, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups, disfavoring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6–92.4 vs. 95.6%, 95% CI, 91.2–97.8, p = 0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted HR of 3.17, 95% CI 1.10–9.11; p = 0.032). Bone health is often forgotten, despite its great impact in survivorship. Our results validate the pathophysiologic link between EBC and bone metabolism, which translates into EBC recurrence. Further research in this area may help refine these findings. Moreover, early identification of women at higher risk for fractures is warranted.
Highlights
As the bone is an endocrine-responsive organ, the decrease in circulating estrogens accelerates bone resorption and aromatase inhibitors (AI) represent a major issue for bone health
This work aimed primarily to assess real-world bone mineral density (BMD) loss associated with the use of AI in early breast cancer (EBC) women and its impact on fracture incidence
As well as time under AI, were relevant independent contributors for fracture incidence, providing important information regarding the deleterious effect of extended therapy with AI on bone health, in older women
Summary
Treatment-Induced Bone Loss (TIBL) in Early Breast Cancer. In early breast cancer (EBC), endocrine therapy (ET) is recommended for all women with detectable expression of estrogen receptors. The choice of ET is primarily defined by the menopausal status, weighting possible side effects and contraindications [1]. In post-menopausal women, aromatase inhibitors (AI) are commonly the adjuvant therapy of choice as they have shown modest but significant increased efficacy and survival when compared with tamoxifen, in large phase III randomized trials and subsequent metaanalysis [2]. AI act by decreasing serum levels of circulating estrogens, blocking the conversion of androgens to estrogen in peripheral tissues, through inhibition of the enzyme aromatase [3]. As the bone is an endocrine-responsive organ, the decrease in circulating estrogens accelerates bone resorption and AI represent a major issue for bone health
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