The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels
Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant fo...
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| Autor*in: |
Opdam, F. L. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2012 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag Berlin Heidelberg 2012 |
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| Übergeordnetes Werk: |
Enthalten in: Cancer chemotherapy and pharmacology - Berlin : Springer, 1978, 71(2012), 3 vom: 11. Dez., Seite 593-601 |
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| Übergeordnetes Werk: |
volume:71 ; year:2012 ; number:3 ; day:11 ; month:12 ; pages:593-601 |
| Links: |
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| DOI / URN: |
10.1007/s00280-012-2034-4 |
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| Katalog-ID: |
SPR003603660 |
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| 024 | 7 | |a 10.1007/s00280-012-2034-4 |2 doi | |
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| 100 | 1 | |a Opdam, F. L. |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels |
| 264 | 1 | |c 2012 | |
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| 337 | |a Computermedien |b c |2 rdamedia | ||
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| 500 | |a © Springer-Verlag Berlin Heidelberg 2012 | ||
| 520 | |a Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. | ||
| 650 | 4 | |a Tamoxifen |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Endoxifen |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Genotype |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Phenotype |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Dextromethorphan |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Breath test |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Dezentje, V. O. |4 aut | |
| 700 | 1 | |a den Hartigh, J. |4 aut | |
| 700 | 1 | |a Modak, A. S. |4 aut | |
| 700 | 1 | |a Vree, R. |4 aut | |
| 700 | 1 | |a Batman, E. |4 aut | |
| 700 | 1 | |a Smorenburg, C. H. |4 aut | |
| 700 | 1 | |a Nortier, J. W. R. |4 aut | |
| 700 | 1 | |a Gelderblom, H. |4 aut | |
| 700 | 1 | |a Guchelaar, H.-J. |4 aut | |
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10.1007/s00280-012-2034-4 doi (DE-627)SPR003603660 (SPR)s00280-012-2034-4-e DE-627 ger DE-627 rakwb eng Opdam, F. L. verfasserin aut The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2012 Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. Tamoxifen (dpeaa)DE-He213 Endoxifen (dpeaa)DE-He213 Genotype (dpeaa)DE-He213 Phenotype (dpeaa)DE-He213 Dextromethorphan (dpeaa)DE-He213 Breath test (dpeaa)DE-He213 Dezentje, V. O. aut den Hartigh, J. aut Modak, A. S. aut Vree, R. aut Batman, E. aut Smorenburg, C. H. aut Nortier, J. W. R. aut Gelderblom, H. aut Guchelaar, H.-J. aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 71(2012), 3 vom: 11. Dez., Seite 593-601 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:71 year:2012 number:3 day:11 month:12 pages:593-601 https://dx.doi.org/10.1007/s00280-012-2034-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 71 2012 3 11 12 593-601 |
| spelling |
10.1007/s00280-012-2034-4 doi (DE-627)SPR003603660 (SPR)s00280-012-2034-4-e DE-627 ger DE-627 rakwb eng Opdam, F. L. verfasserin aut The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2012 Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. Tamoxifen (dpeaa)DE-He213 Endoxifen (dpeaa)DE-He213 Genotype (dpeaa)DE-He213 Phenotype (dpeaa)DE-He213 Dextromethorphan (dpeaa)DE-He213 Breath test (dpeaa)DE-He213 Dezentje, V. O. aut den Hartigh, J. aut Modak, A. S. aut Vree, R. aut Batman, E. aut Smorenburg, C. H. aut Nortier, J. W. R. aut Gelderblom, H. aut Guchelaar, H.-J. aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 71(2012), 3 vom: 11. Dez., Seite 593-601 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:71 year:2012 number:3 day:11 month:12 pages:593-601 https://dx.doi.org/10.1007/s00280-012-2034-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 71 2012 3 11 12 593-601 |
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10.1007/s00280-012-2034-4 doi (DE-627)SPR003603660 (SPR)s00280-012-2034-4-e DE-627 ger DE-627 rakwb eng Opdam, F. L. verfasserin aut The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2012 Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. Tamoxifen (dpeaa)DE-He213 Endoxifen (dpeaa)DE-He213 Genotype (dpeaa)DE-He213 Phenotype (dpeaa)DE-He213 Dextromethorphan (dpeaa)DE-He213 Breath test (dpeaa)DE-He213 Dezentje, V. O. aut den Hartigh, J. aut Modak, A. S. aut Vree, R. aut Batman, E. aut Smorenburg, C. H. aut Nortier, J. W. R. aut Gelderblom, H. aut Guchelaar, H.-J. aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 71(2012), 3 vom: 11. Dez., Seite 593-601 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:71 year:2012 number:3 day:11 month:12 pages:593-601 https://dx.doi.org/10.1007/s00280-012-2034-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 71 2012 3 11 12 593-601 |
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10.1007/s00280-012-2034-4 doi (DE-627)SPR003603660 (SPR)s00280-012-2034-4-e DE-627 ger DE-627 rakwb eng Opdam, F. L. verfasserin aut The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2012 Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. Tamoxifen (dpeaa)DE-He213 Endoxifen (dpeaa)DE-He213 Genotype (dpeaa)DE-He213 Phenotype (dpeaa)DE-He213 Dextromethorphan (dpeaa)DE-He213 Breath test (dpeaa)DE-He213 Dezentje, V. O. aut den Hartigh, J. aut Modak, A. S. aut Vree, R. aut Batman, E. aut Smorenburg, C. H. aut Nortier, J. W. R. aut Gelderblom, H. aut Guchelaar, H.-J. aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 71(2012), 3 vom: 11. Dez., Seite 593-601 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:71 year:2012 number:3 day:11 month:12 pages:593-601 https://dx.doi.org/10.1007/s00280-012-2034-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 71 2012 3 11 12 593-601 |
| allfieldsSound |
10.1007/s00280-012-2034-4 doi (DE-627)SPR003603660 (SPR)s00280-012-2034-4-e DE-627 ger DE-627 rakwb eng Opdam, F. L. verfasserin aut The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2012 Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. Tamoxifen (dpeaa)DE-He213 Endoxifen (dpeaa)DE-He213 Genotype (dpeaa)DE-He213 Phenotype (dpeaa)DE-He213 Dextromethorphan (dpeaa)DE-He213 Breath test (dpeaa)DE-He213 Dezentje, V. O. aut den Hartigh, J. aut Modak, A. S. aut Vree, R. aut Batman, E. aut Smorenburg, C. H. aut Nortier, J. W. R. aut Gelderblom, H. aut Guchelaar, H.-J. aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 71(2012), 3 vom: 11. Dez., Seite 593-601 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:71 year:2012 number:3 day:11 month:12 pages:593-601 https://dx.doi.org/10.1007/s00280-012-2034-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 71 2012 3 11 12 593-601 |
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Enthalten in Cancer chemotherapy and pharmacology 71(2012), 3 vom: 11. Dez., Seite 593-601 volume:71 year:2012 number:3 day:11 month:12 pages:593-601 |
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Enthalten in Cancer chemotherapy and pharmacology 71(2012), 3 vom: 11. Dez., Seite 593-601 volume:71 year:2012 number:3 day:11 month:12 pages:593-601 |
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Opdam, F. L. @@aut@@ Dezentje, V. O. @@aut@@ den Hartigh, J. @@aut@@ Modak, A. S. @@aut@@ Vree, R. @@aut@@ Batman, E. @@aut@@ Smorenburg, C. H. @@aut@@ Nortier, J. W. R. @@aut@@ Gelderblom, H. @@aut@@ Guchelaar, H.-J. @@aut@@ |
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L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="4"><subfield code="a">The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2012</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Springer-Verlag Berlin Heidelberg 2012</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tamoxifen</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Endoxifen</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genotype</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Phenotype</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dextromethorphan</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Breath test</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dezentje, V. 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Opdam, F. L. |
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Opdam, F. L. misc Tamoxifen misc Endoxifen misc Genotype misc Phenotype misc Dextromethorphan misc Breath test The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels |
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The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels Tamoxifen (dpeaa)DE-He213 Endoxifen (dpeaa)DE-He213 Genotype (dpeaa)DE-He213 Phenotype (dpeaa)DE-He213 Dextromethorphan (dpeaa)DE-He213 Breath test (dpeaa)DE-He213 |
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misc Tamoxifen misc Endoxifen misc Genotype misc Phenotype misc Dextromethorphan misc Breath test |
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misc Tamoxifen misc Endoxifen misc Genotype misc Phenotype misc Dextromethorphan misc Breath test |
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The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels |
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The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels |
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Opdam, F. L. |
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Cancer chemotherapy and pharmacology |
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Opdam, F. L. Dezentje, V. O. den Hartigh, J. Modak, A. S. Vree, R. Batman, E. Smorenburg, C. H. Nortier, J. W. R. Gelderblom, H. Guchelaar, H.-J. |
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Elektronische Aufsätze |
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Opdam, F. L. |
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10.1007/s00280-012-2034-4 |
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use of the 13c-dextromethorphan breath test for phenotyping cyp2d6 in breast cancer patients using tamoxifen: association with cyp2d6 genotype and serum endoxifen levels |
| title_auth |
The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels |
| abstract |
Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. © Springer-Verlag Berlin Heidelberg 2012 |
| abstractGer |
Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. © Springer-Verlag Berlin Heidelberg 2012 |
| abstract_unstemmed |
Purpose Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min ($ DOB_{50} $) values of 0.7–0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. © Springer-Verlag Berlin Heidelberg 2012 |
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The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels |
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Dezentje, V. O. den Hartigh, J. Modak, A. S. Vree, R. Batman, E. Smorenburg, C. H. Nortier, J. W. R. Gelderblom, H. Guchelaar, H.-J. |
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| score |
7.4006653 |