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

Ju Won Kim1, Ah Reum Lim1, Ji Young You2

  • 1Division of Medical Oncology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.

Cancer Research and Treatment
|September 13, 2022
PubMed
Abstract

Insights

Activating PIK3CA mutations in HER2-positive breast cancer patients correlate with lower response rates and shorter progression-free survival (PFS) to HER2-targeted therapies. Further research is needed to improve outcomes for these patients.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Activating mutations in the PIK3CA gene are common in breast cancer.
  • These PIK3CA mutations are associated with resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments.
  • HER2-positive (HER2+) breast cancer accounts for a significant proportion of breast cancer cases.

Purpose of the Study:

  • To investigate the correlation between PIK3CA mutations and treatment response in HER2+ breast cancer patients.
  • To compare treatment outcomes, including pathologic complete response (pCR) and progression-free survival (PFS), between patients with wild-type PIK3CA (PIK3CAw) and mutated PIK3CA (PIK3CAm).
  • To assess the impact of PIK3CA mutations on PFS with anti-HER2 monoclonal antibody (mAb) treatment.

Main Methods:

  • Retrospective review of clinical data from 90 HER2+ breast cancer patients receiving HER2-targeted therapy.
  • Comparison of pCR, PFS, and overall survival between PIK3CAw and PIK3CAm groups.
  • Next-generation sequencing to analyze tumor mutational landscape and its association with PFS.

Main Results:

  • 37.8% of patients harbored pathogenic PIK3CA mutations.
  • PIK3CAm group showed lower pCR rates in neoadjuvant chemotherapy for early-stage cancer.
  • PIK3CAm group had significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb and second-line T-DM1 in the metastatic setting.

Conclusions:

  • Activating PIK3CA mutations are linked to diminished treatment response and shorter PFS in HER2+ breast cancer patients receiving palliative HER2-targeted therapy.
  • Patients with PIK3CA mutations require more precise targeted therapies to enhance survival.
  • Understanding the PIK3CA mutational status is crucial for optimizing treatment strategies in HER2+ breast cancer.
Keywords:
Breast neoplasmsHER2PIK3CAPrognosis

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