Background: Factors or signatures predicting response to chemotherapeutic agents are of great interest for breast cancer patient care. There is conflicting data regarding microtubule-associated protein tau as predictive marker of paclitaxel sensitivity. Paclitaxel plays an important role in the adjuvant and metastatic therapy of breast cancer. However, a substantial proportion of patients treated with paclitaxel do not derive benefit from this therapy. Therefore, evaluating potential predictive factors is increasingly important. The authors attempted to validate these findings in vitro utilizing the ATP tumorchemosensitivity assay (ATP-TCA).
Materials and methods: The in vitro drug sensitivity to paclitaxel was evaluated in 48 fresh primary breast cancer specimens using the ATP-TCA. ATP-TCA results were analysed using the area under the curve (AUC) of growth inhibition. These results were correlated with the expression of tau mRNA measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Tau was also compared between patients with progesterone receptor (PgR) positive and negative and estrogen receptor (ER) positive and negative breast cancer, respectively.
Results: The correlation of tau with the AUC for paclitaxel was weak, Spearman Rho was -0.267 with a p-value of 0.064. As described before, multiple regression analysis confirmed T-stage (p = 0.01) and PR status (p = 0.01) as independent predictors of paclitaxel chemosensitivity. Using multiple regression analysis and defining tau mRNA expression as dependent variable estrogen receptor status as measured by immunohistochemistry was a highly significant predictor for tau mRNA expression (p < 0.001). Grade (p = 0.002) as well as PgR expression (p < 0.001) were also found to be predictors of tau mRNA expression. CON- CLUSIONS: In the present data set the authors were not able to show that MAP-tau mRNA could predict benefit from the addition of a taxane to adjuvant chemotherapy. They found that ER expression is associated with tau protein expression. Estrogen gene transcription is reported to carry weak predictive significance for endocrine sensitivity, therefore it might be worth pursuing whether, tau mRNA could possibly be a predictor for endocrine therapy response.