PIK3CA Mutation Predicts Worse Outcomes in HER2+ Breast Cancer

The study covered in this summary was published as a preprint on ssrn.com and has not yet been peer reviewed.

Key Takeaway

  • Researchers observed that PIK3CA mutation was significantly associated with a lower pathologic complete response rate in patients with HER2-positive breast cancer who had received neoadjuvant therapy.

  • In the metastatic setting, PIK3CA mutation also predicted a worse objective response rate, progression-free survival, and time-to-progression. 

Why This Matters

  • PIK3CA mutation occurs frequently in HER2-positive disease (20%–25% of patients), yet the evidence surrounding its significance on cancer or treatment outcomes remains unclear.

  • This meta-analysis suggests PIK3CA mutation does, in fact, affect patient outcomes.

Study Design

  • The researchers searched PubMed, Embase, and the Cochrane Library Central Register of Controlled Trials databases for studies with data on patients with a PIK3CA mutation and various outcome measures in those with HER2-positive breast cancer who had received anti-HER2 therapy.

  • Overall, the researchers identified 43 studies that included 11,099 patients with known PIK3CA mutation status.

Key Results

  • PIK3CA mutation was associated with a lower pathologic complete response rate in the neoadjuvant setting (odds ratio [OR], 0.23; P < .001); the significant association held whether patients received single- or dual-agent anti-HER2 therapy and regardless of hormone receptor status.

  • However, regarding disease-free survival, the authors found no significant association in the adjuvant or neoadjuvant setting. 

  • In the metastatic setting, PIK3CA mutation predicted significantly worse objective response rate (OR, 0.26; P < .001), progression-free survival (hazard ratio [HR], 1.28; P = .024) and time-to-progression (HR, 2.27; P < .001); but the authors did not find a significant association between PIK3CA mutation and overall survival. 

Limitations

  • The anti-HER2 agents administered in each study and methods of assessment of PIK3CA mutation were not uniform. 

  • The number of studies included in several pooled analyses was small. 

Disclosures

  • The study was supported by grants from the National Natural Science Foundation of China, the Sun Yat-Sen University Clinical Research Program, the Guangdong Medical Science and Technology Program, and the Tencent Charity Foundation.

  • The authors declared no conflicts of interest. 

This is a summary of a preprint research study, “Clinical Significance of PIK3CA Mutation in Primary HER2-Positive Breast Cancer Treated with Anti-HER2 Therapy: A Systematic Review and Meta-Analysis.” The study was published as a preprint and has not been peer reviewed. The full text  can be found at ssrn.com.

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