Topoisomerase IIalpha gene status and prediction of pathological complete remission after anthracycline-based neoadjuvant chemotherapy in endocrine non-responsive Her2/neu-positive breast cancer

Abstract

Purpose: Topoisomerase IIalpha (Topo II) is a potential marker of responsiveness to anthracycline-based therapy. We analyzed the role of Topo II gene status in the prediction of pathological complete remission (pCR) after primary anthracycline-based chemotherapy in non- endocrine responsive breast cancers overexpressing Her2/neu.

Methods: Twenty-three patients, with T2-T4, ER and PgR absent, overexpressing Her2/neu breast cancers treated with anthracycline-based chemotherapy were evaluated. Topo II gene status was assessed by FISH in pre-treatment tumor specimens and the results were correlated to pathological and clinical responses.

Results: Overall, six patients had a pCR (26%). Topo II was amplified in 5 (22%) of the tumors. In all patients with Topo II amplification, Her2/neu gene amplification was also detected. Among patients without amplification, one had polysomia of chromosome (Cr) 17 and four patients had deletion of the Topo II gene. A higher probability of pCR was observed when Topo II amplification and Cr 17 polysomy were present: pCR was reported in 3 of 5 amplified tumors (60%), in the polysomic tumor (amplified plus polysomic 67%) and in only 2 out of 13 tumors without alteration of Topo II status (15%). If we compare the frequency of pCR in tumors with amplification or polysomy versus the frequency of tumors with not amplification (deletion or no modification), a significant difference was detected (p=0.02). One progressive disease (PD) was reported in one tumor with Topo II deletion (1/4, 25%) and one in tumor without any modification of Topo II gene status (1/13, 8%).

Conclusions: In patients with endocrine unresponsive and Her2 overexpressing tumors, Topo II amplification or the presence of chromosome 17 polysomy correlate with a significantly high probability of achieving pCR after neoadjuvant, anthracycline-based chemotherapy. Further prospective studies in order to more clearly define the predictive role of Topo II status in this subgroup of patients are warranted.