Acquired tamoxifen resistance in human breast cancer and reduced intra-tumoral drug concentration.
Reduced intra-tumoral drug concentrations have been investigated as a mechanism of tamoxifen resistance in 51 patients with locally recurrent breast cancer. Serum tamoxifen was similar in patients with acquired and de-novo resistance, but intra-tumoral concentrations were significantly lower in patients with acquired resistance. Tumour oestrogen-receptor concentrations at relapse did not support the hypothesis that selective outgrowth of oestrogen-receptor-negative cells is a major mechanism for acquired tamoxifen resistance. Reduced intra-tumoral tamoxifen levels during prolonged therapy may be an important mechanism for acquired resistance in breast cancer.
Johnston
S R
SR
Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
Haynes
B P
BP
Smith
I E
IE
Jarman
M
M
Sacks
N P
NP
Ebbs
S R
SR
Dowsett
M
M
D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000378:metabolism*
D011960:Receptors, Estrogen; D013629:Tamoxifen