TY - JOUR
T1 - Amplification and overexpression of topoisomerase IIα predict response to anthracycline-based therapy in locally advanced breast cancer
AU - Coon, John S.
AU - Marcus, Elizabeth
AU - Gupta-Burt, Shalina
AU - Seelig, Steven
AU - Jacobson, Kris
AU - Chen, Shande
AU - Renta, Vivian
AU - Fronda, Geraldo
AU - Preisler, Harvey D.
PY - 2002/4/1
Y1 - 2002/4/1
N2 - Purpose: The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIα gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. Experimental Design: Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase IIα and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry. Results: Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase IIα amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase IIα amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIα (9 patients) was also associated with favorable response (P = 0.021). Conclusions: Coamplification of erbB-2 and topoisomerase IIα is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIα biology.
AB - Purpose: The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIα gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. Experimental Design: Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase IIα and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry. Results: Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase IIα amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase IIα amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIα (9 patients) was also associated with favorable response (P = 0.021). Conclusions: Coamplification of erbB-2 and topoisomerase IIα is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIα biology.
UR - http://www.scopus.com/inward/record.url?scp=0036554731&partnerID=8YFLogxK
M3 - Article
C2 - 11948114
AN - SCOPUS:0036554731
SN - 1078-0432
VL - 8
SP - 1061
EP - 1067
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -