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Objective: Breast cancer (BC) with chest wall metastasis (CWM) usually shows rich neovascularization.This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2 (HER2)-negative advanced BC involving CWM.Methods: This trial involved four centers in China and was conducted from September 2016 to March 2020.Patients received apatinib 500 mg/d[either alone or with endocrine therapy if hormone receptor-positive (HR+)]until disease progression or unacceptable toxdcity.Progression-free survival (PFS) was the primary endpoint.Results: We evaluated 26 patients for efficacy.The median PFS (mPFS) and median overall survival (mOS) were 4.9[range: 2.0-28.5;95％ confidence interval (95％ CI): 2.1-8.3]months and 18 (range: 3-55;95％ CI: 12.9-23.1)months,respectively.The objective response rate (ORR) was 42.3％ (11/26),and the disease-control rate was 76.9％ (20/26).In the subgroup analysis,HR+ patients compared with HR-negative patients had significantly improved mPFS of 7.0 (95％ CI: 2.2-11.8) months vs.2.3 (95％ CI: 1.2-3.4) months,respectively (P=0.001);and mPFS in patients without or with chest wall radiotherapy was 6.4 (95％ CI: 1.6-19.5) months vs.3.0 (95％ CI: 1.3-4.6) months,respectively (P=0.041).In the multivariate analysis,HR+ status was the only independent predictive factor for favorable PFS (P=0.014).Conclusions: Apatinib was highly effective for BC patents with CWM,especially when combined with endocrine therapy.PFS improved significantly in patients with HR+ status who did not receive chest wall radiotherapy.However,adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.