Factors associated with bone metastasis in breast cancer: a systematic review and meta-analysis

Background: To systematically evaluate and analyze the risk factors for breast cancer (BC) with bone metastasis (BM) and provide clinical evidence supporting the early prevention of BM. Methods: We systematically retrieved databases from the Cochrane Library, PubMed, Web of Science, and EMBASE for BC with BM patient. Limited: publish cation between January 1, 2001, and December 31, 2019. Literature screening and evaluation were performed independently by 2 evaluators. The quality of all included studies was evaluated with the NOS. Studies with NOS >= 6 on factors related to the BM of BC were identified. Weighted odds ratio (OR) were used as the combined effects. Results: We identified 18 articles with available data. The NOS scores ranged from 6-9. Progesterone receptor (PR)-positive BC patients had a relatively lower risk of BM [I-2=45.9%, OR =0.80, 95% confidence interval (CI): 0.72, 0.88, P<0.001]. HER2-positive BC patients had a relatively higher risk of BM (I-2=77.6%, OR =1.35, 95% CI: 1.04, 1.76, P=0.025). The risk of BM in patients with lymph node metastasis was higher than that in patients with no lymph node metastasis (I-2=99.7%, OR =2.60, 95% CI: 1.41, 4.80, P=0.002). The risk of BM in stage T2 BC patients was 1.99 times that in stage T1 BC patients (I-2=96.8%, OR =1.99, 95% CI: 1.03, 3.83, P=0.040). The risk of BM in stage T3 BC patients was 4.74 times that in stage T1 BC patients (I-2=95.6%, OR =4.74, 95% CI: 1.94, 11.57, P=0.001). The risk of BM in stage T4 BC patients was 14.57 times that in stage T1 BC patients (I-2=95.4%, OR =14.57, 95% CI: 4.16, 51.05, P<0.001). The incidence of BM in BC patients without lobular or ductal BC was significantly higher than that in patients with ductal BC (I-2=56.4%, OR =1.26, 95% CI: 1.09, 1.45, P=0.001). Discussion: Patients with PR-positive BC have a relatively lower risk of BM. Patients with HER2-positive, lymph node metastasis-positive, nonlobular, or ductal BC have a relatively higher risk of BM. With increasing T stage, the risk of BM in BC patients also increases.