Finally, we show that as the number of detached breast tumor cells composing a three-dimensionally growing cellular mass increases, Mek activity and ErbB2 expression are lost and the resulting ErbB2-deficient cells display resistance to trastuzumab, an anti-ErbB2 antibody normally used for treatment of ErbB2-positive breast cancer. The gene discussed is ERBB2; the disease is breast neoplasm.