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@ARTICLE{Mrdter:306679,
      author       = {T. E. Mürdter and W. Schroth and M. P. Goetz and R.
                      Tremmel and S. Igel and E. Schaeffeler and S. Jäger and S.
                      Loibl and A. Gerteis and L. Pfaff and C. Bechtner and D.
                      Wrobel and I. Bernhöft and I. Fischer and C. Meisner and M.
                      Block and H. Brauch$^*$ and M. Schwab$^*$},
      collaboration = {G. T. C. Group},
      othercontributors = {C. Bechtner and I. Bernhöft and V. Bjelic-Radisic and M.
                          Burkhardt and M. Darsow and G. Deutsch and T. Dewitz and W.
                          Dietz and M. Eichbaum and E. Faust and T. Göhler and S.-T.
                          Graßhoff and J. Hackmann and C. Hänle and A. Hartkopf and
                          B. Heinrich and C. Kahl and G. Kaltenecker and A.
                          Kleine-Tebbe and H.-C. Kolberg and T. Krauß and T. Kühn
                          and G. Kunz and A. Ligl-Löhner and M. Negwer and U. Rhein
                          and G. Rogmans and J. Rom and S. Schmatloch and M.
                          Schwab$^*$ and G. Stalzer and A. Stefek and H.-J.
                          Strittmatter and J. Terhaag and C. Uleer and K. Wimmer-Freys
                          and D. Wrobel and D.-M. Zahm},
      title        = {{S}upplementation of {T}amoxifen with {L}ow-{D}ose
                      {E}ndoxifen in {P}atients with {B}reast {C}ancer with
                      {I}mpaired {T}amoxifen {M}etabolism ({TAMENDOX}): {A}
                      {R}andomized {C}ontrolled {P}hase {I}/{II} {T}rial.},
      journal      = {Clinical cancer research},
      volume       = {31},
      number       = {23},
      issn         = {1078-0432},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2025-02672},
      pages        = {4903 - 4911},
      year         = {2025},
      abstract     = {:Tamoxifen undergoes bioactivation to its active metabolite
                      (Z)-endoxifen, which blocks estrogen-dependent breast tumor
                      growth at high potency. We tested the feasibility and safety
                      of supplementing standard tamoxifen therapy with low-dose
                      (Z)-endoxifen in patients with breast cancer with
                      compromised tamoxifen bioactivation.:We conducted a
                      prospective, interventional, three group randomized trial
                      including 235 patients with hormone receptor-positive breast
                      cancer who received standard tamoxifen therapy (20 mg/day).
                      Patients were stratified by CYP2D6 genotype (n = 78),
                      defining poor, intermediate, and normal metabolizers, or by
                      baseline (Z)-endoxifen plasma concentration (n = 78),
                      defining ≤15, 15 to 25, and ≥25 nmol/L. Co-treatment
                      with (Z)-endoxifen 3 and 1.5 mg/day or placebo was
                      performed, respectively. A control group (n = 79) received
                      placebo regardless of metabolizer phenotype. The primary
                      endpoint was the number of patients with (Z)-endoxifen
                      levels >32 nmol/L after 6 weeks of treatment. Adverse events
                      were continuously monitored.A higher proportion of patients
                      in both intervention groups achieved target concentrations
                      >32 nmol/L compared with control (P < 0.0001). At 3 mg
                      (Z)-endoxifen supplementation, $92.3\%$ of CYP2D6 poor
                      metabolizer patients and all patients with baseline
                      (Z)-endoxifen ≤15 nmol/L achieved the target
                      concentration. At 1.5 mg (Z)-endoxifen supplementation,
                      $88\%$ of CYP2D6 intermediate metabolizer patients and
                      $95\%$ of patients with 15 to 25 nmol/L baseline
                      (Z)-endoxifen levels achieved the target concentration.
                      Similar proportions of patients receiving (Z)-endoxifen
                      (6/80, $7.5\%)$ or placebo (8/155, $5.2\%)$ experienced
                      grade 3 adverse events.Adding low-dose (Z)-endoxifen to
                      standard tamoxifen is safe and provides a new approach to
                      personalized antiestrogen treatment for patients with low
                      endoxifen plasma levels.},
      keywords     = {Humans / Female / Breast Neoplasms: drug therapy / Breast
                      Neoplasms: pathology / Breast Neoplasms: genetics / Breast
                      Neoplasms: metabolism / Tamoxifen: administration $\&$
                      dosage / Tamoxifen: analogs $\&$ derivatives / Tamoxifen:
                      pharmacokinetics / Tamoxifen: adverse effects / Middle Aged
                      / Cytochrome P-450 CYP2D6: genetics / Aged / Adult /
                      Antineoplastic Agents, Hormonal: administration $\&$ dosage
                      / Antineoplastic Agents, Hormonal: adverse effects /
                      Prospective Studies / Treatment Outcome / Aged, 80 and over
                      / Genotype / Tamoxifen (NLM Chemicals) / Cytochrome P-450
                      CYP2D6 (NLM Chemicals) / 4-hydroxy-N-desmethyltamoxifen (NLM
                      Chemicals) / Antineoplastic Agents, Hormonal (NLM
                      Chemicals)},
      cin          = {TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)TU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41036998},
      doi          = {10.1158/1078-0432.CCR-25-2103},
      url          = {https://inrepo02.dkfz.de/record/306679},
}