Effect Of Mutations In Distinct Components Of The Pi3k/Akt/Mtor Pathway On Sensitivity To Endocrine Therapy In Estrogen Receptor (Er)-Positive Breast Cancer.

532 Background: Aberrations of the PI3K/AKT/mTOR pathway are common in ER-positive breast cancer and may be associated with endocrine-resistance. We hypothesized that, since the majority of ER-positive breast cancers are actually sensitive to endocrine therapy, the most prevalent aberration in this pathway will more likely be associated with endocrine-sensitivity rather than resistance. Methods: We studied 28 tumors from patients enrolled on protocol NCT00570921 using fulvestrant and everolimus after aromatase inhibitor failure; 19 from 13 patients with endocrine-sensitive disease and 9 from 8 patients with resistant tumors. Resistance was defined as relapse within 3 years of adjuvant use or progression within 6 months in the metastatic setting. DNA was extracted from FFPE tumor tissue and subjected to next-generation-based comprehensive genomic profiling using the FoundationOne assay and alterations were then compared. Results: 10 of 13 patients with endocrine-sensitive tumors (77%) had at least one alte...