Unknown

Dataset Information

0

Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen.


ABSTRACT: Low steady-state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor-positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z-endoxifen and Z-4-hydroxy-tamoxifen (Z-4OHtam), with treatment outcomes in an independent cohort of BC patients. Among all patients, metabolite levels did not affect survival. However, in the premenopausal subgroup receiving tamoxifen alone (n = 191) we confirmed an inferior BC -specific survival in patients with the previously described serum concentration threshold of Z-4OHtam ≤ 3.26 nm (HR = 2.37, 95% CI = 1.02-5.48, P = 0.039). The 'dose-response' survival trend in patients categorized to ordinal concentration cut-points of Z-4OHtamoxifen (≤ 3.26, 3.27-8.13, > 8.13 nm) was also replicated (P-trend log-rank = 0.048). Z-endoxifen was not associated with outcome. This is the first study to confirm the association between a published active tamoxifen metabolite threshold and BC outcome in an independent patient cohort. Premenopausal patients receiving 5-year of tamoxifen alone may benefit from therapeutic drug monitoring to ensure tamoxifen effectiveness.

SUBMITTER: Helland T 

PROVIDER: S-EPMC8024735 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4308646 | biostudies-literature
| S-EPMC10358080 | biostudies-literature
| S-EPMC6312049 | biostudies-literature
| S-EPMC4872319 | biostudies-literature
| S-EPMC7105402 | biostudies-literature
| S-EPMC7830894 | biostudies-literature
| S-EPMC3909953 | biostudies-literature
| S-EPMC8885431 | biostudies-literature
| S-EPMC3805021 | biostudies-literature
| S-EPMC9328423 | biostudies-literature