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).

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Recent experimental studies indicate that bone fractures result in the release of cytokines and cells that promote metastasis. Obtaining observational data on bone fractures after breast cancer diagnosis related to distant breast cancer recurrence risk could help determine whether fall prevention strategies can contribute to reduce breast cancer mortality. We used data from the largest German statutory health insurance fund (Techniker Krankenkasse) in a population-based cohort study of breast cancer patients diagnosed between January 2015 and November 2019. ICD-10 codes were documented monthly to quarterly. Fractures diagnosed simultaneous or after the initial breast cancer and metastases diagnosed initially from half a year later on served as exposure and outcome, respectively. The risk of regional, distant non-bone or bone metastasis related to a fracture was modelled by adjusted conditional logistic regression analysis. Of 154,000 breast cancer patients, 82,039 had a follow-up time of more than half a year. During follow-up, fractures were diagnosed in 11,900 (14.5%) patients and regional or distant metastases occurred in 7,011 (8.5%). The risk for a metastasis was reduced in patients, who had a fracture (OR 0.57, 95% CI 0.53, 0.62) compared to patients without, particularly for lymph node metastasis and moderately less pronounced in bone-metastasis (OR 0.69, 95% CI 0.61, 0.79). In view of the positive effects of sports on health of cancer survivors, the present results will decrease the anxiety of breast cancer patients that risking bone fractures might have a negative impact on their disease-specific outcome.