Abstract PD1-2: PIK3CA mutations and/or low PTEN predict resistance to combined anti-HER2 therapy with lapatinib and trastuzumab and without chemotherapy in TBCRC006, a neoadjuvant trial of HER2-positive breast cancer patients

摘要: We have recently reported that in patients with HER2-positive breast cancer, neoadjuvant targeted therapy lapatinib and trastuzumab to more completely block the HER receptor layer, combined endocrine (in ER-positive tumors) without chemotherapy led a substantial 27% pathologic complete response (pCR) rate breast. Activation of downstream signaling pathways may lead resistance therapies targeting pathway receptors. Aberrant activation PI3K via decreased levels PTEN and/or presence activating PIK3CA mutations has been implicated anti-HER2 therapy, but results clinical trials are all confounded by co-administration inconsistent. sought clarify role these variables predicting pCR, surrogate for long-term outcome, treated potent alone prospective Phase II trial cancer. Patients large tumors (median 6 cm) were given 12 weeks plus followed surgery (Rimawi et al. JCO, 2013). Serial tissue biopsies obtained from study participants. For this study, we focused on baseline pre-treatment characteristics. protein measured IHC scored using H-score. identified extracted DNA multiplex PCR next generation sequencing (the Ion Torrent 50-gene cancer mutation panel). Of 64 evaluable patients, was available 59 IHC, sufficient 33 panel. median H-score 100 (range 0-300). status when dichotomized correlated pCR (32% high vs. 9% low PTEN, p = 0.04). Activating out (36%; 3 helical 9 catalytic domain) independent ER status. None whose harbored achieved (p 0.06). There no association between suggesting they 0.44). When considered together status, there 31 cases data both. The overall cohort 16% (lower than observed trial). However, 0/17 (0%) expression ( conclude HER2 as result either or combination trastuzumab. This is first report patient samples chemotherapy. If validated larger cohort, our findings suggest positive who also harbor aberrant benefit addition PI3K/Akt/mTOR inhibitors blockade. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD1-2.