Herein disclosed are methods that are predictive of resistance to endocrine therapy in an estrogen receptor-positive (ER-positive) breast cancer patient. An exemplary method comprises detecting the overexpression of MN/CA9 gene expression product(s) in a sample from an affected subject, wherein if MN/CA9 is overexpressed, then the subject is considered to have a greater probability of resistance to endocrine therapy, particularly tamoxifen, and a corresponding poorer prognosis if undergoing endocrine therapy, than if MN/CA9 is not overexpressed. MN/CA9 gene expression products useful in the predictive/prognostic methods include MN/CA IX, MN proteins/polypeptides, MN nucleic acids and soluble MN/CA IX antigen (s-CA IX). The methods are useful as an aid in the selection of treatment for a patient with an ER-positive breast tumor. The methods of the invention can be used, for example, to identify those patients requiring additional/alternative therapies, preferably, but not necessarily, therapies that are not affected by acidic pH. The methods also comprise the use of diagnostic/prognostic imaging to detect MN/CA IX in a patient tumor, wherein the presence of MN/CA IX in one or more tumors is indicative of probable resistance to antiestrogen therapy, particularly to tamoxifen.