Topoisomerase IIalpha gene status and prediction of pathological complete remission after anthracycline-based neoadjuvant chemotherapy in endocrine non-responsive Her2/neu-positive breast cancer.
OBJECTIVE
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.
Orlando
Laura
L
Research Unit Medical Senology, European Institute of Oncology, Milan, Italy. laura.orlando@ieo.i
Del Curto
Barbara
B
Gandini
Sara
S
Ghisini
Raffaella
R
Pietri
Elisabetta
E
Torrisi
Rosalba
R
Balduzzi
Alessandra
A
Cardillo
Anna
A
Dellapasqua
Silvia
S
Veronesi
Paolo
P
Viale
Giuseppe
G
Goldhirsch
Aron
A
Colleoni
Marco
M
D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D012189:Retrospective Studies
D018943:Anthracyclines; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases