Lei Huo

The University of Texas MD Anderson Cancer Center, USA

Title: PTEN expression and copy number variation in triple-negative breast cancer

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Biography

Abstract

With recent advances in targeting the PI3K pathway, it is essential to understand the changes of PTEN expression over the course of the disease in patients with triple-negative breast cancer (TNBC) and whether PTEN copy number variation by next generation sequencing can serve as an alternative to immunohistochemistry to identify PTEN loss. We compared PTEN expression by immunohistochemistry between pretreatment tumors and residual tumors after neoadjuvant chemotherapy in 96 patients in a TNBC clinical trial. A correlative analysis between PTEN expression and PTEN copy number by next generation sequencing was also performed. PTEN expression was discordant between pretreatment and posttreatment primary tumors in 5% of patients, and between posttreatment primary tumors and lymph node metastases in 9%. Intratumoral heterogeneity for PTEN loss was observed in 7% of the patients. Among pretreatment tumors, PTEN copy numbers were significantly higher in the PTEN-positive tumors by immunohistochemistry compared with the PTEN-loss tumors (p<0.0001). However, PTEN-positive and PTEN-loss tumors overlapped in copy numbers. Testing various specimens by immunohistochemistry may generate different PTEN results in a small proportion of patients with TNBC, therefore the decision of testing one versus multiple specimens in a clinical trial should be defined in the patient inclusion criteria. Although a distinct cutoff by which copy number variation differentiated PTEN-positive tumors from those with PTEN loss was not identified, our findings suggest that higher copy number of PTEN may confer positive PTEN, whereas those with lower copy number of PTEN would need additional testing to assess PTEN loss.