Germline mutation in the KLRC2 gene to inform intrinsic resistance and inferior responses to trastuzumab in breast cancer.

e12078Background: Trastuzumab elicit high response rates among individuals with HER2 positive breast cancer. However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic variation affecting an individual’s response to trastuzumab. Although cancers used be classified according to their somatically acquired driver mutations, germline alterations can also directly modulate the responses of such cancers to targeted therapies and can strongly influence clinical outcomes. To correlate the variable clinical features of HER2 positive breast cancer with germline alterations, we studied the whole genome of 22 patients. Methods: All the 22 patients have been treated by trastuzumab within second-line salvage treatment, in which 16 patients received trastuzumab as first-line treatment. Among them,11 patients keep continuous benefit from trastuzumab while the others showed intrinsic resistance (we called intrinsic resistance as getting progression within 16 weeks during the...