Abstract 1207: A systematic literature review of the prevalence of PIK3CA mutations and mutation hotspots in HR+/HER2- metastatic breast cancer

Abstract

Introduction: Clinical research on the predictive value of PIK3CA mutations in hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2–) metastatic breast cancer (mBC) has advanced in recent years. However, knowledge of epidemiological prevalence has not been systematically evaluated. This study aimed to report prevalence of PIK3CA mutation using different biopsy techniques as well as specific hotspot mutations across the available literature. 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 detailing the prevalence of PIK3CA mutations 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. Most included studies (n = 18) were observational in nature. A total of 4,247 samples were tested for genetic mutations. Most studies used tissue biopsy samples (n = 33; 89%). Tumor samples accounted for 84.6% of all samples (n = 3597). Liquid biopsies were performed in 4 studies (11%) and accounted for 15.3% of all samples (n = 650). One study reported both liquid and tumor biopsy data. Overall, reported prevalence of the PIK3CA mutation ranged from 13.3% to 61.5%. Median prevalence was 36.4% (25th percentile = 28.6%; 75th percentile = 48.4%). Among studies using tissue biopsies, the majority reported prevalence from 16.7% to 61.5%. Among studies using liquid biopsies, the majority (n = 3) reported prevalence from 43.3% to 46.8%; one other study reported 13.3%. The most commonly tested hotspot mutations were H1047R and E545K. Among studies reporting specific hotspot mutation prevalence (n = 9), the H1047R hotspot mutation prevalence in these studies ranged between 25% and 75% while the E545K prevalence ranged between 11.1% and 50%. Conclusions: Although discrepancies exist with respect to mutation prevalence estimated across various tissue vs. liquid biopsy techniques, PIK3CA mutations and mutation hotspots (specifically H1047R and E545K) frequently occur in HR+/HER2– mBC. Citation Format: Lea Mollon, Alejandra Aguilar, Elizabeth Anderson, Joni Dean, Lisa Davis, Terri Warholak, Ayal A. Aizer, Emma Platt, Aditya Bardiya, Derek Tang. A systematic literature review of the prevalence of PIK3CA mutations and mutation hotspots in HR+/HER2- metastatic breast cancer [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 1207.

Endocrine-Resistant Breast Cancer: Mechanisms and Treatment

“…Somatic mutations in genes encoding for components of the PI3K/ AKT occur in up to 70% of breast cancers and include mutations or amplification of the catalytic (p110) subunits of PI3K as well as mutations of PI3K modulators, such as the phosphatase and tensin homolog (PTEN), AKT, and mTOR [29,30]. PIK3CA is mutated in up to 40% of human breast cancers and most alterations occur within the kinase (H1047R) and helical domains (E542K and E545K) of p110α resulting in hyperactivation of PI3K [31,32]. The prognostic impact of PI3CA mutations is still unclear: while in early ER-positive/HER2-negative breast cancer, an association with an increased diseasefree survival has been reported, they seem to decrease prognosis in the advanced setting [33][34][35].…”

Frequency and spectrum of PIK3CA somatic mutations in breast cancer

“…Activating mutations in the PIK3CA are found in approximately 30-40% of patients with cancer and induce hyperactivation of the alpha isoform (p110α) of the phosphatidylinositol 3-kinase (PI3K) [1][2][3]. In patients with HR+/HER2− BC, mTOR/mTOR pathway has been associated with endocrine therapy resistance [4].…”

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer

“…In patients with HR þ , HER2 À ABC, approximately 40% have disease with a mutation in phosphatidylinositol-4,5bisphosphate 3-kinase catalytic subunit alpha (PIK3CA; refs. [24][25][26][27][28]. The PIK3CA gene encodes the catalytic p110a isoform, belonging to class IA PI3K (29).…”