Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab.

Indeed, the TRYPHAENA trial observed a lower pCR rate in HER2 + breast cancer patients whose tumors housed mutated PIK3CA (49% pCR) as compared with those expressing wild-type PIK3CA (64% pCR); however, this effect did not reach statistical significance ( P =0.17). 48 As discussed previously, constitutive activation of the PI3K/AKT pathway drives the aberrant growth and survival of HER2 + breast cancers, and as such, future studies need to monitor the mutational status of PIK3CA and other downstream effectors as novel predictors of resistance to pertuzumab-based therapies. 48 , 49 Mechanisms of resistance to anti-HER2 therapy Compensatory changes in HER2 and co-receptor expression Resistance to anti-HER2 therapy can transpire at multiple points along the HER2 signaling systems.

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