HER2 Support Group Forums - View Single Post - Tamoxifen, LHRH agonist, AI, oophorectomy??

Jackie07 · 02-11-2012, 05:24 PM

Clin Pharmacol Ther. 2011 May;89(5):718-25. Epub 2011 Mar 23.
Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes.

Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP.
Source

Cancer Prevention and Control Program, Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California, USA.

Abstract

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study.

We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen.

For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)).

The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold.

[About endoxifen: http://www.sciencedaily.com/releases...1211141838.htm]

02-11-2012, 05:24 PM	#5
Jackie07 Senior Member Join Date: Jan 2008 Location: "Love never fails." Posts: 5,808	Re: Tamoxifen, LHRH agonist, AI, oophorectomy?? Clin Pharmacol Ther. 2011 May;89(5):718-25. Epub 2011 Mar 23. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP. Source Cancer Prevention and Control Program, Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California, USA. Abstract We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)). The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold. [About endoxifen: http://www.sciencedaily.com/releases...1211141838.htm] __________________ Jackie07 http://www.kevinmd.com/blog/2011/06/doctors-letter-patient-newly-diagnosed-cancer.html http://www.asco.org/ASCOv2/MultiMedi...=114&trackID=2 NICU 4.4 LB Erythema Nodosum 85 Life-long Central Neurocytoma 4x5x6.5 cm 23 hrs 62090 semi-coma 10 d PT OT ST 30 d 3 Infertility tmts 99 > 3 u. fibroids > Pills CN 3 GKRS 52301 IDC 1.2 cm Her2 +++ ER 5% R. Lmptmy SLNB+1 71703 6 FEC 33 R Tamoxifen Recc IIB 2.5 cm Bi-L Mast 61407 2/9 nds PET 6 TCH Cellulitis - Lymphedema - compression sleeve & glove H w x 4 MUGA 51 D, J 49 M Diastasis recti Tamoxifen B. scan Irrtbl bowel 1'09 Colonoscopy 313 BRCA1 V1247I hptc hemangioma Vertigo GI - > yogurt hysterectomy/oophorectomy 011410 Exemestane 25 mg tab 102912 ~ 101016 stopped due to r. hip/l.thigh pain after long walk DEXA 1/13 1-2016 lesions in liver largest 9mm & 1.3 cm onco. says not cancer. 3-11 Appendectomy - visually O.K., a lot of puss. Final path result - not cancer. Start Vitamin D3 and Calcium supplement （600mg x2) 10-10 Stopped Exemestane due to r. hip/l.thigh pain OKed by Onco 11-08-2016 7-23-2018 9 mm groundglass nodule within the right lower lobe with indolent behavior. Due to possible adenocarcinoma, Recommend annual surveilence. 7-10-2019 CT to check lung nodule. 1-10-2020 8mm stable nodule on R Lung, two 6mm new ones on L Lung, a possible lymph node involvement in inter fissule. "I WANT TO BE AN OUTRAGEOUS OLD WOMAN WHO NEVER GETS CALLED AN OLD LADY. I WANT TO GET SHARP EDGED & EARTH COLORED, TILL I FADE AWAY FROM PURE JOY." Irene from Tampa Advocacy is a passion .. not a pastime - Joe Last edited by Jackie07; 02-11-2012 at 05:31 PM..