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PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic
Daphne Gschwantler-Kaulich1, Yen Y Tan1,2, Eva-Maria Fuchs3
1Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.
Background:
Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients.
Methods:
Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months.
Results:
Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS.
Conclusion:
In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.
Insights
Phosphatase and tensin homologue (PTEN) positivity is linked to progressive disease in advanced Her-2+ breast cancer patients receiving trastuzumab therapy. PTEN status did not impact progression-free or overall survival in this patient group.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Trastuzumab is effective for early-stage Her-2+ breast cancer.
- 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance.
- Loss of phosphatase and tensin homologue (PTEN) may cause resistance via aberrant signaling.
Purpose of the Study:
- To investigate the relationship between PTEN expression and trastuzumab response.
- To analyze PTEN's role in Her-2 overexpressing metastatic breast cancer.
Main Methods:
- 164 Her-2+ metastatic breast cancer patients receiving trastuzumab-based therapy (2000-2007).
- PTEN status analyzed by immunohistochemistry in 115 tumor tissues.
- Associations with histopathological parameters, response rate, progression-free survival (PFS), and overall survival (OS) assessed.
Main Results:
- PTEN positive in 80 patients (69.6%), PTEN negative in 35 (30.4%).
- PTEN expression associated with p53 (p=0.041).
- Significantly more progressive disease observed in PTEN-positive patients (p=0.018), no significant correlation with PFS or OS.
Conclusions:
- PTEN positivity is significantly associated with progressive disease in Her-2-positive metastatic breast cancer.
- PTEN status did not correlate with progression-free or overall survival.
- PTEN may play a role in trastuzumab resistance mechanisms.
