AUTHOR=Chao Ta-Chung , Tsai Yi-Fang , Liu Chun-Yu , Lien Pei-Ju , Lin Yen-Shu , Feng Chin-Jung , Chen Yen-Jen , Lai Jiun-I. , Hsu Chih-Yi , Lynn Jiun Jen , Huang Chi-Cheng , Tseng Ling-Ming 

TITLE=Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1192946

DOI=10.3389/fonc.2023.1192946

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Breast cancer is the most common cancer type that affects women. In hormone receptor–positive (HR+), human epidermal growth factor receptor 2−negative (HER2–) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (<italic>PIK3CA)</italic> is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of <italic>PIK3CA</italic> mutations in the Taiwanese breast cancer population.</p></sec><sec><title>Methodology</title><p>This is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of <italic>PIK3CA</italic> mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment.</p></sec><sec><title>Results</title><p><italic>PIK3CA</italic> mutations were identified in 278 of 728 patients (38%). <italic>PIK3CA</italic> mutations were reported in 43% of patients with HR−/HER2+ subtype and 42% of patients with HR+/HER2– postmenopausal status. A lower prevalence of <italic>PIK3CA</italic> mutations was observed in triple-negative (27%) and HR+/HER2– premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the <italic>PIK3CA</italic> mutation cohort and 16 months (95% CI: 11-23 months) in the <italic>PIK3CA</italic> wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the <italic>PIK3CA</italic> mutation cohort and 6 months (95% CI: 2-9 months) in the <italic>PIK3CA</italic> wild-type cohort.</p></sec><sec><title>Conclusion</title><p>A high frequency of <italic>PIK3CA</italic> mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of <italic>PIK3CA</italic> mutations might influence therapeutic decisions, leading to better treatment outcomes.</p></sec>