Abstract 2193: Biopsy and analytical testing methods used to identify PIK3CA mutations in hormone receptor-positive, human epidermal growth factor receptor-negative metastatic breast cancer: A systematic literature review
Authors: Anderson Elizabeth , Mollon Lea , Aguilar Alejandra , Dean Joni , Davis Lisa , Warholak Terri , Aizer Ayal , Platt Emma , Bardiya Aditya , Tang Derek 
Published: August 2018

Introduction: This study aimed to identify biopsy and analytical testing methods for PIK3CA mutation in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) via a systematic literature review. Understanding the available biopsy and analytical methods for PIK3CA mutation and its publication trends over time may support understanding of emerging technology trends.

Methods: A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts was performed by two independent researchers that included, but was not limited to, keywords: “breast neoplasm,” “PIK3CA protein,” “hormone receptor positive,” and “metastases.” English-language studies in HR+, HER2- mBC reporting either biopsy or analytical testing methods for PIK3CA mutation and published between January 1993 through August 2017 were included. Content analysis was employed to quantify collected data elements.

Results: Of 558 studies included for full-text review, 36 met inclusion criteria. Total number of samples tested among this subgroup were 4,247 (tumor = 3,597; liquid = 650). Sample size ranged from 9 to 618 (median = 47). The most common methods used for identifying PIK3CA mutations were tumor biopsies (n = 33) while liquid biopsies only occurred in four studies. One study reported both liquid and tumor biopsy data. Formalin-fixed, paraffin-embedded (FFPE) tissue samples were used in most studies examining tumor samples (n = 28). Among liquid biopsies, circulating tumor cells (CTC) (n = 2), cell-free DNA (cfDNA) (n = 1), and circulating tumor DNA (ctDNA) (n = 1) were used. Techniques for DNA analyses included PCR (n = 14), NGS (n = 14), Sanger (n = 7), mass spectrometry (n = 5) and liquid chip technology (n = 1). Some studies used multiple methods (n = 5). Most studies using NGS were cross-sectional (n = 9); other studies using NGS (n=4) were clinical trials. Among clinical trials (n = 9), four used PCR only (sample size range 30 to 550), two used NGS only (sample size range 16 to 28), one used Sanger sequencing only (sample size = 21) and two used both NGS and PCR methods (sample size range 26 to 55). Of fourteen studies using NGS, thirteen were published from 2015 to 2017, which may be indicative of a transition to newer methodology. While PCR remained a commonly used analytical method regardless of sample size, NGS has become more common than PCR in recent publication years.

Conclusions: The majority of studies utilized PCR for PIK3CA analytical testing despite newer technologies available. NGS methodology was used more frequently in more recent publications. However, the relative accuracy between PCR and NGS testing is yet to be fully understood.

Citation Format: Elizabeth Anderson, Lea Mollon, Alejandra Aguilar, Joni Dean, Lisa Davis, Terri Warholak, Ayal Aizer, Emma Platt, Aditya Bardiya, Derek Tang. Biopsy and analytical testing methods used to identify PIK3CA mutations in hormone receptor-positive, human epidermal growth factor receptor-negative metastatic breast cancer: A systematic literature review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2193.