Taken together, the results of our study identify a novel positive feedback loop mechanism downstream of the canonical TGFβ/Smad signaling axis, mediated by a breast cancer anti-estrogen resistance gene, BCAR3. We report a novel role of BCAR3 to antagonize Smad signaling, efficiently leading to inhibition of the TGFβ’s biological functions in breast cancer cells. The gene discussed is TGFB1; the disease is breast cancer.