Benefit to neoadjuvant anti–Human Epidermal Growth Factor Receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status
A partir d'échantillons tumoraux prélevés sur 429 patientes atteintes d'un cancer du sein HER2+ de stade précoce et incluses dans l'essai Neo-ALLTO, cette étude montre que la perte d'expression de PTEN ne permet pas de prédire l'apparition d'une résistance au trastuzumab ou au lapatinib
Background : Assessment of PTEN might be an important tool in identifying HER2-positive breast cancer patients unlikely to derive benefit from anti-HER2 therapies. However, studies to date have failed to demonstrate its predictive role in any treatment setting.
Patients and methods : Prospectively collected baseline core biopsies from 429 early-stage HER2-positive breast cancer patients treated with trastuzumab, lapatinib or their combination in the Neo-ALTTO study were stained using two anti-PTEN monoclonal antibodies (CST and DAKO). The association of PTEN status and PI3K pathway activation (defined as either PTEN loss and/or PIK3CA mutation) with total pathological complete response (tpCR) at surgery, event-free survival (EFS) and overall survival (OS) were evaluated.
Results : PTEN loss was observed in 27% and 29% of patients (all arms, n=361 and n=363) for CST and DAKO, respectively. PTEN loss was more frequently observed in hormone receptor (HR)-negative (33% and 36% with CST and DAKO, respectively) compared to HR-positive tumours (20% and 22% with CST and DAKO, respectively). No significant differences in tpCR rates were observed according to PTEN status. PI3K pathway activation was found in 47% and 48% of patients (all arms, n=302 and n=301) for CST and DAKO, respectively. Similarly, tpCR rates were not significantly different for those with or without PI3K pathway activation. Neither PTEN status nor PI3K pathway activation were predictive of tpCR, EFS, or OS, independently of treatment arm or HR status. High inter-antibody and inter-observer agreements were found (>90%). Modification of scoring variables significantly affected the correlation between PTEN and HR status but not with tpCR.
Conclusion : These data show that PTEN status determination is not a useful biomarker to predict resistance to trastuzumab and lapatinib-based therapies. Lack of standardization of PTEN status determination may influence correlations between expression and relevant clinical endpoints.
Annals of Oncology , résumé, 2015