Provided herein is a method for determining whether a human subject with breast cancer will respond to a therapy comprising a tyrosine kinase inhibitor or a biologic. The method includes determining the expression level and/or activation level of various signal transduction molecules such as truncated HER2 protein, full-length HER2 protein, HER3 protein, PI3K protein, and others. The determination of likely response to a tyrosine kinase inhibitor therapy or a biologic therapy involves comparing the expression level and/or activation level of the signal transduction molecule(s) to a reference expression/activation level for the specific signal transduction molecule(s).