Secreted phospholipase A2 group IIa (sPLA2-IIa) has been shown to promote tumor genesis and cell proliferation. The properties of this group of enzymes are utilized in liposomal drug delivery of chemotherapy. sPLA2-IIa is also under investigation as a possible treatment target in itself, and as a prognostic marker. The expression of sPLA2-IIa in breast cancer has not been examined extensively, and never using immunohistochemistry. We sought to investigate the expression of sPLA2-IIa in a cohort of advanced breast cancer patients with correlation to known clinicopathologic risk factors and survival. Material from 525 breast cancer patients (426 primary tumors and 99 metastases or local recurrences) was examined for sPLA2-IIa expression using immunohistochemistry. Out of these, 262 showed expression of sPLA2-IIa. We found that there was no correlation to clinicopathologic characteristics, and no impact of sPLA2-IIa expression on prognosis. However, we found that a large proportion of patients in our study had high levels of sPLA2-IIa expression, and that sPLA2-IIa was equally expressed in primary tumors and metastases. These findings may be significant in the future development of liposomal drug delivery or targeted sPLA2-IIa treatment.
PurposeAnthracyclines remain a cornerstone in the treatment of primary and advanced breast cancer (BC). This study has evaluated the predictive value of a multigene mRNA-based drug response predictor (DRP) in the treatment of advanced BC with epirubicin. The DRP is a mathematical method combining in vitro sensitivity and gene expression with clinical genetic information from > 3000 clinical tumor samples.MethodsFrom a DBCG cohort, 140 consecutive patients were treated with epirubicin between May 1997 and November 2016. After patient informed consent, mRNA was isolated from archival formalin-fixed paraffin-embedded primary breast tumor tissue and analyzed using Affymetrix arrays. Using time to progression (TTP) as primary endpoint, the efficacy of epirubicin was analyzed according to DRP combined with clinicopathological data collected retrospectively from patients’ medical records. Statistical analysis was done using Cox proportional hazards model stratified by treatment line.ResultsMedian TTP was 9.3 months. The DRP was significantly associated to TTP (P = 0.03). The hazard ratio for DRP scores differing by 50 percentage points was 0.55 (95% CI –0.93, one-sided). A 75% DRP was associated with a median TTP of 13 months compared to 7 months following a 25% DRP. Multivariate analysis showed that DRP was independent of age and number of metastases.ConclusionThe current study prospectively validates the predictive capability of DRP regarding epirubicin previously shown retrospectively allowing the patients predicted to be poor responders to choose more effective alternatives. Randomized prospective studies are needed to demonstrate if such an approach will lead to increased overall survival.
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