Abstract P2-09-27: Integrated analysis of PTEN protein expression and PI3KCA mutations as predictors for pathological complete response in HER2-positive breast cancer
Authors: Gavila J , Gozalbo F , Climent MA , Guerrero AL , Sandiego S , Blanch S , Algarra MA , Soriano V , Guillem V , Ruiz A , Lopez Guerrero JA 
Published: February 2018

Introduction: Anti-HER2 treatment has also influenced the response to neoadjuvant chemotherapy in HER2-positive breast cancer (BC) by increasing the pathologic complete response (pCR) rate. The activation of HER2 signaling causes the downstream activation of the PI3K/AKT/mTOR pathway that plays a crucial role in developing resistance to trastuzumab (T). Therefore, candidate biomarkers with a potential role in the prediction of a pCR and prognosis after anti-HER2 treatment could be selected from this pathway.

Material and Methods: We retrospectively evaluated PTEN protein expression and PI3KCA mutations in core biopsies from HER2-positive patients treated at our institution with neoadjuvant therapy based on anthracyclines, paclitaxel and T. Protein expression was assessed by immunohistochemistry and used as dichotomic variable, PTEN loss was considered if Hscore ≤ 40. The association of PTEN status, PI3KCA mutation and PI3K activation (defined as either PTEN loss and/or presence of PI3KCA) with pathological complete response (ypT0/isN0) and progression-free survival (PFS) was evaluated.

Results: In our database 86 patients with HER2-positive clinical stage II-III BC were identified. Median follow-up was 75.85 months. PTEN was available from 84 (97.7%) and PI3KCA genotype from 67 patients (77.9%). Median age was 47.34, stage III 58.8% and 50% were hormonal receptor (HR) positive. Low PTEN was described in 29.8% tumors and was statistically associated with Grade1-2 and HR positive tumors. PI3KCA mutations (exon 9 and 20) were observed in 23.9% tumors. PI3K activation was detected in 37.5% tumors. Overall, the pCR rate was 53.5%. In low PTEN tumors pCR was 12% and in PTEN-high tumors, it was 72.1% (p&lt;.0001). pCR rate was statistically different between PIK3CA mutant and wild-type tumors (6.3% vs. 51.9%; p&lt;.0001). PI3K activation was statistically associated with lower pCR rate (12.5 vs. 72.9%; p&lt;.0001). In multivariable analysis adjusted for baseline parameters, HR expression (OR 4.170; 95% CI 0.975-17.829;p=0.054) and PI3K activation (OR 45.87; 95% CI8.059-261.101; p&lt;.0001) independently predicted pCR. In univariable analysis clinical, stage III, non-pCR and PI3K activation were correlated with worse PFS. PI3K activation was statistically associated with lower PFS at 5 years (OR 3.813;CI 95%1.369-10.347; p=0.009) in the multivariable analysis.

Conclusions: The study showed the potential role of PIK3CA Genotype and PTEN expression in predicting pCR and prognosis after anthracycline–taxane-based chemotherapy and anti-HER2 treatment.

Citation Format: Gavila J, Gozalbo F, Climent MA, Guerrero AL, Sandiego S, Blanch S, Algarra MA, Soriano V, Guillem V, Ruiz A, Lopez Guerrero JA. Integrated analysis of PTEN protein expression and PI3KCA mutations as predictors for pathological complete response in HER2-positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-27.