Background: 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. They decrease bone mineral density, accelerate osteoporosis and lead to increased risk of fractures, thus impairing quality of life. Identification of patients at higher risk would be helpful for best treatment decisions. Recommendations have been published for bone health preservation but real-world data regarding implementation and adherence to these recommendations is scarce. This work aimed to assess bone loss, fracture incidence and risk factors associated with these events, as well as the prognostic influence of fractures in women undertaking adjuvant AI.

Materials and Methods: In this retrospective cohort study, we have evaluated women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. A minimum of 3 months under AI and 3 years of follow-up after AI start were necessary for inclusion. Statistical analysis of collected data was performed using R 3.5.2, R-Studio 1.1.456 and Stata 15.1 software.

Results: 451 eligible women were reviewed (median age 68 years, 30-98 min-max). Median time under AI was 40 months (3-114). Baseline bone densitometry, carried out in only 69% patients, showed abnormal results in 75%, but only 69% and 16% started calcium/vitD supplementation and bisphosphonates therapy, respectively. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in women with higher age (p=0.006). This group also showed lower T-scores at lumbar spine and femoral neck (p=0.067). On multivariate analysis, age (OR 1.04, 95% CI 1.01-1.07, p=0.016) and time under AI (OR 1.02, 95% CI 1.00-1.03, p=0.045) were independent predictors of fracture events, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups disfavouring 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).

Conclusion: Bone health is often forgotten, despite its great impact in survivorship. Our results suggest a pathophysiologic link between EBC and bone metabolism, potentially estrogen-mediated, which translates into EBC recurrence. Further research in this area may help refining these findings. Moreover, early identification of women at higher risk with individualized treatment plans comprising shorter duration of AI is warranted. Poor adherence to existing guidelines is a crucial barrier to effective approaches to bone health.

Citation Format: Leonor Vasconcelos Matos, Maria Teresa Neves, Fatima Alves, Mafalda Baleiras, André Ferreira, Pedro Cotovio, Tiago Dias Domingues, Mariana Malheiro, Joana Graça, Leonor Fernandes, Ana Plácido, Helena Miranda, Ana Martins. From theory to practice: Impact of aromatase inhibitors in the bone health of women with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-27.