Topoisomerase IIalpha-positive and BRCA1-negative phenotype: association with favorable response to epirubicin-based regimens for human breast cancers.
Epirubicin exerts its anti-tumor effect through binding to topoisomerase IIalpha (TOP2A) and inducing DNA double-strand breaks. BRCA1 is involved in the repair of these breaks. We investigated the relationship between TOP2A or BRCA1 immunohistochemical expression and pathological response in 108 primary breast cancers treated with epirubicin-based regimens. The pCR (pathological complete response) rate for TOP2A-positive (17%) was significantly (P < 0.005) higher than for TOP2A-negative (2%), while the pCR rate for BRCA1-negative (11%) was non-significantly higher than for BRCA1-positive (5%). The pCR rate of TOP2A-positive and BRCA1-negative (30%) was significantly higher than for TOP2A-negative and BRCA1-positive (3%; P < 0.05), or TOP2A-negative and BRCA1-negative (0%; P < 0.005). The TOP2A-positive and BRCA1-negative phenotype associates with a favorable response to epirubicin-based regimens.
Miyoshi
Yasuo
Y
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Kurosumi
Masafumi
M
Kurebayashi
Junichi
J
Matsuura
Nariaki
N
Takahashi
Masato
M
Tokunaga
Eriko
E
Egawa
Chiyomi
C
Masuda
Norikazu
N
Kim
Seung Jin
SJ
Okishiro
Masatsugu
M
Yanagisawa
Tetsu
T
Ueda
Satsuki
S
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Noguchi
Shinzaburo
S
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010641:Phenotype; D000075223:Poly-ADP-Ribose Binding Proteins; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D015251:Epirubicin; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human