Abstract
BackgroundEven 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.MethodsBetween 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.ResultsEighty 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.ConclusionIn Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.
Highlights
Overexpression of Her-2 is found in approximately 25% of human breast cancers leading to an aggressive phenotype and poor patient survival [1,2,3,4]
We found a significant association of the expression of phosphatase and tensin homologue (PTEN) and p53 (p = 0.041), while there was no association with grading, hormone receptor status, insulin like growth factor receptor (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 progression free survival (PFS) or overall survival (OS)
Summary
Overexpression of Her-2 is found in approximately 25% of human breast cancers leading to an aggressive phenotype and poor patient survival [1,2,3,4]. One of the known mechanisms underlying trastuzumab’s antitumor activity is the downregulation of p185ErbB2 and the subsequent inhibition of its downstream PI3K-Akt and MAPK signalling pathways. Molecules located in these pathways are thought to be associated with unresponsiveness to trastuzumab. 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
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