Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data

Haizhu Chen; Xingbin Hu; Daquan Wang; Ying Wang; Yunfang Yu; Herui Yao

doi:10.1016/j.tranon.2023.101738

Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data

Transl Oncol. 2023 Nov:37:101738. doi: 10.1016/j.tranon.2023.101738. Epub 2023 Aug 17.

Authors

Haizhu Chen¹, Xingbin Hu¹, Daquan Wang², Ying Wang¹, Yunfang Yu³, Herui Yao⁴

Affiliations

¹ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Centre, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.
² Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
³ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Centre, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China; Faculty of Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China. Electronic address: yuyf9@mail.sysu.edu.cn.
⁴ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Centre, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China. Electronic address: yaoherui@mail.sysu.edu.cn.

Abstract

Background: This study aimed to comprehensively explore the clinical significance of PIK3CA mutation in human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with anti-HER2 therapy.

Methods: We systematically searched PubMed, Embase, and the Cochrane databases for eligible studies assessing the association between PIK3CA mutation and outcomes in patients with HER2-positive breast cancer receiving anti-HER2 therapy. The main outcomes included: (1) pathological complete response (pCR) or disease-free survival (DFS) for the neoadjuvant setting; (2) DFS or invasive DFS for the adjuvant setting; (3) objective response rate (ORR), progression-free survival (PFS), time-to-progression (TTP), or overall survival (OS) for the metastatic setting. The mutational landscape of HER2-positive breast cancer according to PIK3CA mutation status was examined based on TCGA breast cancer dataset.

Results: Totally, 43 eligible studies, covering 11,099 patients with available data on PIK3CA mutation status, were identified. In the neoadjuvant setting, PIK3CA mutation was significantly associated with a lower pCR rate (OR=0.23, 95% CI 0.19-0.27, p<0.001). This association remained significant irrespective of the type of anti-HER2 therapy (single-agent or dual-agent) and hormone receptor status. There were no significant differences in DFS between PIK3CA mutated and wild-type patients in either the neoadjuvant or adjuvant settings. In the metastatic setting, PIK3CA mutation predicted worse ORR (OR=0.26, 95%CI 0.17-0.40, p<0.001), PFS (HR=1.28, 95%CI 1.03-1.59, p = 0.024) and TTP (HR=2.27, 95%CI 1.54-3.34, p<0.001). However, no significant association was observed between PIK3CA mutation status and OS. Distinct mutational landscapes were observed in HER2-positive breast cancer between individuals with PIK3CA mutations and those with wild-type PIK3CA.

Conclusions: PIK3CA mutation was significantly associated with a lower pCR rate in HER2-positive breast cancer treated with neoadjuvant anti-HER2 therapy. In the metastatic setting, PIK3CA mutation was predictive of worse ORR, PFS and TTP. These results suggest the potential for developing PI3K inhibitors as a therapeutic option for these patients.

Keywords: Anti-HER2 therapy; Breast cancer; HER2-positive; PIK3CA mutation; Predictive.