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KMID : 0939920230550020531
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대한암학회지
2023 Volume.55 No. 2 p.531 ~ p.541
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PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
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Kim Ju-Won
Lim Ah-Reum
You Ji-Young
Lee Jung-Hyun
Song Sung-Eun
Lee Nam-Kwon
Jung Seung-Pil
Cho Kyu-Ran
Kim Cheol-Yong
Park Kyong-Hwa
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Abstract
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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 (PIK3CAm). 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.
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KEYWORD
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PIK3CA, Breast neoplasms, HER2, Prognosis
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