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Background Adriamycin-based neoadjuvant chemotherapy is widely used in HER2- breast cancer patients, however, some patients have no response or acquire resistance to these regimens. Therefore, it is important to screen patients who respond to adriamycin with biomarkers. Methods A human lncRNA microarray analysis followed by a quantitative real-time polymerase chain reaction (qRT-PCR) assay was utilized to identify the differentially expressed lncRNAs. The proliferation viability of cells transfected with or without CTB 104H12.5 was measured by CCK-8 and clone formation assay, cell apoptosis and cell cycle were evaluated by Flow cytometry. And the expression of RNA and proteins was tested by qRT-PCR and Western blot, respectively. Results Ten whole blood samples from HER2- breast cancer patients who received docetaxel combined with adriamycin regimen were enrolled, a human lncRNA microarray analysis showed that the low expression of CTB-104H12.5 was associated unfavorable prognosis. And the mRNA and protein level of CTB-104H12.5 is much lower in MCF-7/ADR cells than that of MCF-7 cells while CTB-104H12.5 knockdown in MCF cells induces cell resistance to adriamycin, while CTB-104H12.5 overexpression in MCF7/ADR cells reversed their resistance to adriamycin. Also, the mRNA and protein levels of GAS7C were associated with CTB-104H12.5. Conclusions Low expression of CTB-10412.5 predicted resistance to adriamycin in HER2 negative breast cancer, which may serve as a potential biomarker to dynamically monitor adriamycin resistance for breast cancer patients.