Journal of Breast Cancer

Korean Breast Cancer Society (한국유방암학회)
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PIK3CA Mutations and Neoadjuvant Therapy Outcome in Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Sequential Analysis

  • Seo, Youjeong (Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Yeon Hee (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ahn, Jin Seok (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Im, Young-Hyuck (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Nam, Seok Jin (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Cho, Soo Youn (Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Cho, Eun Yoon (Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2018.05.24
  • Accepted : 2018.09.19
  • Published : 2018.12.31
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Abstract

Purpose: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers. Methods: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients. Results: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in postNAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016). Conclusion: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.

Keywords

References

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