Our findings may provide a basic mechanism to explain the lack of TGF-β responsiveness and anti-estrogen-dependent growth inhibition in some of ERα-positive infiltrating breast carcinoma, support an idea of both tumor suppressing and enhancing effects of TGF-β in the development and/or progression of breast cancer, and open a path to further investigate the cause of aberrant expression of Smad4 in ERα-positive infiltrating breast carcinoma. Here, ESR1 is linked to breast carcinoma.