PIK3CA Mutation Is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients.

Ju Won Kim; Ah Reum Lim; Ji Young You; Jung Hyun Lee; Sung Eun Song; Nam Kwon Lee; Seung Pil Jung; Kyu Ran Cho; Cheol Yong Kim; Kyong Hwa Park

Purpose Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. Materials and Methods We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK-3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. Results Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 patients (37.8%) had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. Conclusion Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

HER2 positive breast cancer; CANCER patients; EPIDERMAL growth factor receptors; BREAST cancer; CANCER treatment

Cancer Research & Treatment, 2023, Vol 55, Issue 2, p531

1598-2998

Academic Journal

10.4143/crt.2022.221