Topoisomerase II alpha and TLE3 as predictive markers of response to anthracycline and taxane-containing regimens for neoadjuvant chemotherapy in breast cancer

Abstract

PurposeAnthracyclines and taxanes are considered the standard for neoadjuvant chemotherapy of breast cancer, although they are often associated with serious side effects and wide variability of individual response. In this study, we analyzed the value of topoisomerase II alpha (TOP2A) and transducin-like enhancer of split 3 (TLE3) as predictive markers of response to therapy with anthracyclines and taxanes.Materials and methodsTOP2A and TLE3 protein expressions were evaluated using immunohistochemistry on 28 samples, obtained by core needle biopsy in patients with locally advanced breast carcinoma, subsequently subjected to epirubicin- and paclitaxel-based neoadjuvant chemotherapy. The immunohistochemical staining was correlated with the clinical response measured by the tumor size reduction evaluated by breast magnetic resonance imaging, prior and after chemotherapy, and by pathologic evaluation of the surgical specimen.ResultsNeoadjuvant chemotherapy achieved a size reduction in 26/28 tumors (92.9%), with an average percentage decrease of 45.6%. A downstaging was achieved in 71.4% of the cases of locally advanced carcinoma. TOP2A positivity was correlated with a greater reduction in tumor diameter (P=0.06); negative staining for TLE3 was predictive of a better response to neoadjuvant chemotherapy (P=0.07). A higher reduction in tumor diameter (P=0.03) was also found for tumors that were concurrently TLE3-negative and TOP2A-positive.ConclusionTOP2A and TLE3 showed a correlation with response to neoadjuvant chemotherapy. While TOP2A is a well-known marker of response to anthracyclines-based chemotherapy, TLE3 is a new putative predictor of response to taxanes. Data from the current study suggest that TOP2A and TLE3 warrant further investigation in a larger series as predictors of response to neoadjuvant chemotherapy for locally advanced breast carcinoma.

The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer

“…However, no standard antibodies, staining procedure, and scoring system have been recommended. Various cut-off values such as 5% [ 29 ], 10% [ 30 ], 15% [ 31 ], 20% [ 26 ], and 30% [ 32 ] have been applied in different studies. Other studies took both the staining intensity and percentage of positive cells into consideration to defined TOP2A status [ 33 ].…”

Differential Regulation of TLE3 in Sertoli Cells of the Testes during Postnatal Development

“…Villanueva et al reported that TLE3 has two contradictory functions during transcriptional activity in adipogenesis [27]. TLE3 also regulates metabolism and cell fate in the bone [28,29,30], pancreas [31,32,33], muscle [34], embryonic stem cell [35,36], and cancer [17,27,37,38,39]. It is interesting to note that the relative level of TLE3 in the testes is much higher than that in other tissues.…”

miR-34a expression in human breast cancer is associated with drug resistance

“…The TOP-2a gene is located on the 17q21-q22 region and is the target of anthracycline drugs. Changes in intracellular TOP-2a expression and activity form another important mechanism of breast cancer resistance to chemotherapy [ 30 ]. The HER-2 gene is located adjacent to the TOP-2a gene and promotes cell proliferation by participating in transmembrane signal transduction in a variety of ways.…”