Metastatic Breast Cancer Recurrence after Bone Fractures

SIMPLE SUMMARY: Bone fractures bear potential risk to promote metastatic relapse in breast cancer. We conducted a population-based cohort study of 84,300 breast cancer patients diagnosed between January 2015 and November 2019. Bone fracture after breast cancer diagnosis was associated with an increased metastasis risk. Fractures may pose an increased risk to developing metastasis. Potential clinical implications for cancer patients are in support of fall prevention programs. ABSTRACT: Experimental studies suggest that bone fractures result in the release of cytokines and cells that might promote metastasis. Obtaining observational data on bone fractures after breast cancer diagnoses related to distant breast cancer recurrence could help to provide first epidemiological evidence for a metastasis-promoting effect of bone fractures. We used data from the largest German statutory health insurance fund (Techniker Krankenkasse, Hamburg, Germany) in a population-based cohort study of breast cancer patients with ICD-10 C50 codes documented between January 2015 and November 2019. The risk of metastasis overall, regional, distant non-bone or bone metastasis related to a fracture was modeled by an adjusted discrete time-to-event analysis with time-dependent exposure. Of 154,000 breast cancer patients, 84,300 fulfilled the inclusion criteria and had a follow-up time of more than half a year. During follow-up, fractures were diagnosed in 13,579 (16.1%) patients. Metastases occurred in 7047 (8.4%) patients; thereof 1544 had affected regional lymph nodes only and 5503 distant metastases. Fractures demonstrated a statistically significant association with subsequent metastasis overall (adjusted HR 1.12, 95% CI 1.04, 1.20). The highest risk for metastasis was observed in patients with subsequent bone metastasis (adjusted HR 1.18, 95% CI 1.05, 1.34), followed by distant non-bone metastasis (adjusted HR 1.16, 95% CI 1.07, 1.26) and lymph node metastasis (adjusted HR 1.08, 95% CI 0.97, 1.21).