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. 2023 Aug 15:13:1192946.
doi: 10.3389/fonc.2023.1192946. eCollection 2023.

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

Ta-Chung Chao  1   2   3 , Yi-Fang Tsai  1   2   4 , Chun-Yu Liu  1   2   5 , Pei-Ju Lien  1   4 , Yen-Shu Lin  1   4 , Chin-Jung Feng  1   4 , Yen-Jen Chen  1   2   4 , Jiun-I Lai  1   6   7 , Chih-Yi Hsu  2   8 , Jiun Jen Lynn  9 , Chi-Cheng Huang  1   4   10 , Ling-Ming Tseng  1   2   4
Affiliations

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

Ta-Chung Chao et al. Front Oncol. .

Abstract

Background: 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 (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population.

Methodology: 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 PIK3CA 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.

Results: PIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR-/HER2+ subtype and 42% of patients with HR+/HER2- postmenopausal status. A lower prevalence of PIK3CA 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 PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA 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 PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort.

Conclusion: A high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes.

Keywords: PIK3CA mutations; Taiwanese population; advanced breast cancer; hotspot mutations; next-generation sequencing.

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Conflict of interest statement

Author JL is full time employee of Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare his study was supported by Novartis Pharmaceuticals Corporation. The funder was involved in the study design and medical writing assistance was provided by Caamin Arora, M Pharm, from Novartis Pharmaceuticals Corporation, India.

Figures

Figure 1
Figure 1
Study design. * Baseline characteristics collection period from HER. ABC, advanced breast cancer; BC, breast cancer; CDK4/6, cyclin-dependent 4 or 6 kinase; EBC, early breast cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; EHC, electronic health record; NGS, next-generation sequencing; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; y, years.
Figure 2
Figure 2
Patient distribution.
Figure 3
Figure 3
Mutation map of genes in the PI3K/AKT/mTOR pathway. AKT, serine/threonine kinase; HR, hormone receptor; HER2, human epidermal growth factor receptor 2; mTOR, mammalian target of rapamycin; PI3K, phosphoinositide 3-kinase; PIK3CA/PIK3CB, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta; PIK3R1, phosphoinositide-3-kinase regulatory subunit 1; PTEN, phosphatase and TENsin homolog; TSC, tuberous sclerosis complex.
Figure 4
Figure 4
Prevalence of PIK3CA mutation in each IHC cohort. HR, hormone receptor; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; TNBC, triple-negative breast cancer.
Figure 5
Figure 5
(A) Distribution of PIK3CA variants frequency. *A total of 16.9% of mutations in patients from this study were not captured by the therascreen PIK3CA Rotor-Gene Q (RGQ) PCR Kit. The most frequent mutations not captured were E726K (2.8%) and N345K (5.3%). Mutation Q546E was not detected (0%) at exon 9. (B) OncoPrinter plot of PIK3CA mutations. PI3K, phosphoinositide 3-kinase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.
Figure 6
Figure 6
(A) Product-limit survival estimates of CDK4/6 inhibitors. (B) Product-limit survival estimates of everolimus (an mTOR inhibitor). CDK4/6, cyclin-dependent 4 and 6 kinase; mTOR, mammalian target of rapamycin; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.
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