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PAI-1 and HER2 interaction in advanced breast cancer disease: evidence for added benefit from trastuzumab in HER2-negative patients.
- Source :
-
Cancer Chemotherapy & Pharmacology . Jun2015, Vol. 75 Issue 6, p1289-1301. 13p. - Publication Year :
- 2015
-
Abstract
- Purpose: The urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor 1 (PAI-1) are associated with an aggressive course in breast cancer and are used to determine whether chemotherapy is needed in node-negative patients. The objective of the study was to evaluate the prognostic value of uPA and PAI-1 protein expression in advanced breast cancer patients treated with trastuzumab. Methods: Formalin-fixed paraffin-embedded tumor tissue samples were retrospectively collected from 230 patients with advanced breast cancer treated with trastuzumab and 130 patients treated with 1st line taxanes. uPA, PAI-1, ER, PgR, HER2 and Ki67 protein expression was evaluated by immunohistochemistry. Results: Central review of HER2 status revealed that only 144 (63 %) of the trastuzumab-treated patients were truly HER2-positive. Median survival was 50.7 months for the HER2-positive and 30.1 months for the HER2-negative patients ( p = 0.006) treated with trastuzumab. In multivariate Cox regression analysis of the trastuzumab cohort, a significant interaction was found, in terms of survival, between HER2 status and PAI-1 protein expression in the stroma (Wald's p = 0.002). Positive PAI-1 protein expression in the stroma of HER2-negative patients was associated with lower risk of death (HR 0.35, 95 % CI 0.19-0.65, Wald's p = 0.0008). Such an association was not observed in HER2-positive patients treated with trastuzumab or in the non-trastuzumab (validation) cohorts. Conclusions: Our results suggest that positive stromal PAI-1 protein expression may identify a subgroup of HER2-negative advanced breast cancer patients who might benefit from treatment with trastuzumab. Further studies are warranted to validate these findings in larger cohorts. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03445704
- Volume :
- 75
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Cancer Chemotherapy & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 102856197
- Full Text :
- https://doi.org/10.1007/s00280-015-2762-3