Abstract P4-14-08: Serum concentrations of tamoxifen and Z-endoxifen may predict sexual dysfunction in the 2nd year of adjuvant endocrine treatment

Autor: Gunnar Mellgren, Ea Lien, S Lunde, E Bifulco, BH Gripsrud, K Lode, RA Lind, SS Hustad, J Jonassen, Håvard Søiland, JT Kvaløy, NS Gebreslase, ME Haugstøyl, Emiel A. M. Janssen, Tone Hoel Lende, Turid Aas, Thomas Helland, KB Hagen
Rok vydání: 2019
Předmět:
Zdroj: Cancer Research. 79:P4-14
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.sabcs18-p4-14-08
Popis: Background and rationale: Side effects of adjuvant treatment with tamoxifen (tam) may impair Quality of Life (QoL) and have been suggested as an independent variable for discontinuation of tam1. There are large inter-patient variabilities in prevalence and severance of side effects among tam users. Therefore, there is a need for biological markers that can predict side effects. A potential biological predictor is the serum concentrations of tam and/or its metabolites. In this prospective observational study we have analyzed serum concentrations of tam and 9 metabolites over 3 years. Patients Reported Outcome Measures (PROM) were obtained to elucidate possible associations between side effects, adherence and tam metabolism. Methods: Breast cancer patients using adjuvant tam (20mg/d) were recruited through the Prospective Breast Cancer Biobank project between 2011 and 2016. Inclusion criteria were ER positive status, ≥ 6 months tam use, tumor size of ≥0.1 cm and being able to read and write Norwegian. Concentration levels of tam and metabolites in serum were analyzed by LC-MS/MS2 and adherence data were collected through the Norwegian prescription database. PROM-data comprised of validated questioners reporting side effects of endocrine treatment and QoL. Statistical analyses comprised non-parametric tests, logistic regression, chi square tests and the Benjamin-Hochberg procedure to correct for multiple testing. Results: Associations between metabolite concentrations and side effects were run as a cross sectional analysis (N=149) and separate analysis of each year of follow-up with 85, 77 and 65 patients at the 1st, 2nd and 3rd year respectively. We found that 78 % of patients reported side effects, 66 % reported mood swings, 21 % reported severe hot flushes and 71 % reported decreased libido. When analyzing years separately, we found that on the 2nd year patients experiencing vaginal dryness had significantly higher levels of tamoxifen (P=0.032, after correction for multiple testing and adjustment for clinical relevant variables) compared to patients not experiencing vaginal dryness. Also, on year 2 the patients in the lower quartile of Z-endoxifen (≤17.9 nM) had significantly lower libido (p=0.015) compared to patients with Z-endoxifen levels >17.9 nM after adjustment for clinical relevant variables and correction for multiple testing. Analyses regarding adherence are not complete and more results will be presented in the poster. Discussion: Our data indicates that high serum concentrations of tam and low concentrations of Z-endoxifen are associated with vaginal dryness and sexual dysfunction. Patients reporting “very low libido” had the highest levels of tam, suggesting that slow metabolic conversion and accumulation of tam may contribute to sexual dysfunction. Our results were only significant in the second year of follow-up, possibly because patients wait to resume sexual activity after diagnosis, chemo and surgery. After receiving advice (i.e. lubricants), the symptoms are often reduced in the subsequent follow-up (3rd year). In conclusion, our results indicate that monitoring tam serum concentrations may be used to predict side effects. 1 Owusu C. et al. JCO. 2008 2 Helland T. et al. BCR. 2017 Citation Format: Helland T, Haugstøyl ME, Hagen KB, Kvaløy JT, Lunde S, Lode K, Lind RA, Gripsrud BH, Bifulco E, Gebreslase NS, Jonassen J, Hustad SS, Aas T, Lende TH, Lien EA, Janssen EA, Mellgren G, Søiland H. Serum concentrations of tamoxifen and Z-endoxifen may predict sexual dysfunction in the 2nd year of adjuvant endocrine treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-08.
Databáze: OpenAIRE
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