Response to mitoxantrone in advanced breast cancer: correlation with expression of c-erbB-2 protein and glutathione S-transferases.
Sixty-eight patients with advanced breast cancer were treated with mitoxantrone and clinical responses assessed. Expression of c-erbB-2 protein and cytosolic glutathione S-transferase (GST) isoenzymes pi, alpha and mu by the primary tumours of these patients was determined immunohistochemically, and correlated with treatment response. Tumours overexpressing c-erbB-2 (n = 16, 23%) showed a lower response rate (50% vs 58%) and shorter duration of response to treatment, compared with c-erbB-2 negative tumours. These associations were not statistically significant but survival following start of treatment was significantly shorter in the c-erbB-2 positive group. For each GST isoenzyme, the response rate and duration of response of the group showing enzyme expression did not differ significantly from those with negatively staining tumours. These data do not support a role for expression of GSTs alone in resistance to mitoxantrone monotherapy in advanced breast cancer. The poorer post treatment survival of patients with c-erbB-2 positive tumours suggests they could be selected for more intensive treatment regimens.
Division of Pathology, University of Newcastle upon Tyne, UK.
C
C
Wright
J
J
Cairns
B J
BJ
Cantwell
A R
AR
Cattan
A G
AG
Hall
A L
AL
Harris
C H
CH
Horne
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use*; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D016019:Survival Analysis
D005982:Glutathione Transferase; D007527:Isoenzymes; D008942:Mitoxantrone; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases