PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib
2011

PI3K Pathway Activation and Drug Resistance in HER2-Positive Breast Cancer

Sample size: 67 publication Evidence: moderate

Author Information

Author(s): Wang Leiping, Zhang Qunling, Zhang Jian, Sun Si, Guo Haiyi, Jia Zhen, Wang Biyun, Shao Zhimin, Wang Zhonghua, Hu Xichun

Primary Institution: Fudan University Shanghai Cancer Center

Hypothesis

The study explores the relationship between PI3K pathway activation and the sensitivity to lapatinib in HER2-positive metastatic breast cancer patients.

Conclusion

PI3K pathway activation may lead to drug resistance to lapatinib and trastuzumab.

Supporting Evidence

  • PIK3CA mutations were found in 12.3% of patients.
  • PTEN loss was detected in 31.6% of patients.
  • Patients with PI3K pathway activation had a lower clinical benefit rate of 36.4% compared to 68.6% in those without activation.
  • The overall response rate was 9.1% for patients with activation versus 31.4% for those without.
  • PI3K pathway activation correlated with a shorter median progression-free survival of 4.5 months.

Takeaway

This study found that some breast cancer patients have changes in their genes that make their treatment less effective.

Methodology

The study involved 67 HER2-positive metastatic breast cancer patients treated with lapatinib and capecitabine, with tumor specimens analyzed for PI3K pathway status.

Limitations

The study had a relatively small sample size and focused only on specific mutations.

Participant Demographics

Median age of participants was 49 years, with a range from 26 to 75 years.

Statistical Information

P-Value

0.017

Confidence Interval

95% CI, 5.7-7.3 months

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1471-2407-11-248

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