Background: The PI3K/AKT/mTOR signaling pathway plays a key role for the growth and survival of breast cancer cells and aberrations such as phosphatidylinositol-3-kinase (PI3KCA) mutations are common. BKM120 is an oral pan-class I PI3KCA inhibitor. The aim of this study was to evaluate neoadjuvant treatment with BKM120 in PI3KCA mutated early breast cancer in order to assess the effect in PI3K/Akt/mTOR signalling pathway.

Methods: Patients (pts) with previously untreated invasive, non-metastatic histologically confirmed breast cancer, with a tumor size ≥ 1,5cm and non-urgent surgical treatment were enrolled. Only women with ER+ / HER2- and PI3KCA gene mutated were eligible. Patients received treatment with BKM120 (100mg/day; administered orally) during 4 weeks. Subsequently, surgery was performed. Inmunohistochemical analysis of pAkt and pS6 (the H-score intensity x%) as well as KRAS mutation were evaluated on tumor tissue at surgery. H score < 150 was related with inactivation of PI3K signalling pathway.

Results: To date 24 patients has been included in the study (median age, 52,5 years; range 38-69 years;). 13 out of 24 (54%) had PI3KCA mutated and 8 have completed BKM120 treatment. PI3KCA mutation: Exon 20, 4 pts; exon 9, 2 pts; exon 4, 1 pts and exon 20 and 9, 1 pts. One patient discontinued treatment due to adverse event (nausea grade 2). The most relevant adverse events included transitory increase of transaminases. No serious or grade 4 adverse events were observed. Preliminary results of 7 pts showed inactivation of pAkt (H score < 150) in 2 pts with no change in the reminder 5 pts (median H score 300).

Conclusion: Our preliminary data shown that four weeks of BKM120 treatment do not inactivate PI3K/Akt/mTOR signalling pathway, measured throughout pAkt in ER+/HER2-/PI3KCA mutated breast cancer pts. However, we cannot draw any conclusion because the small number of pts included so far. KRAS mutation and pS6 analysis will be presented along with updated results.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-15-09.