Benefit–risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John’s wort in breast cancer patients

References

• Lorizio W, Wu AHB, Beattie MS, Rugo H, Tchu S, Kerlikowske K. Clinical and biomarker predictors of side effects from tamoxifen. Breast Cancer Res Treat 2012;132:1107–18
   PubMed Web of Science ®Google Scholar
• Hadji P. Improving compliance and persistence to adjuvant tamoxifen and aromatase inhibitor therapy. Crit Rev Oncol Hematol 2010;73:156–66
   PubMed Web of Science ®Google Scholar
• Fallowfield L. Acceptance of adjuvant therapy and quality of life issues. Breast 2005;14:612–16
   PubMed Web of Science ®Google Scholar
• NAMS. The 2017 hormone therapy position statement of the North American Menopause Society. Menopause 2017;24:1–26
   PubMedGoogle Scholar
• European Union herbal monograph on Cimicifuga racemosa (L.). Nutt., Rhizoma [Internet]. 2018; Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Herbal_monograph/2017/08/WC500233056.pdf
   Google Scholar
• Beer A-M, Neff A. Differentiated evaluation of extract-specific evidence on Cimicifuga racemosa's efficacy and safety for climacteric complaints. Evid Based Complement Alternat Med 2013;2013:860602
   PubMed Web of Science ®Google Scholar
• Beer A-M. Cimicifuga racemosa bei klimakterischen Beschwerden – Aktuelle Daten bestätigen Wirksamkeit und Sicherheit. Z Phytother 2015;36:10–17
   Google Scholar
• Stoll W. Phytotherapeutikum beeinflußt atrophisches Vaginalepithel: Doppelblindversuch Cimicifuga vs. Oestrogenpräparat. Therapeutikon 1987;1:23–31
   Google Scholar
• Osmers R, Friede M, Liske E, Schnitker J, Freudenstein J, Henneicke-von Zepelin HH. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol 2005;105:1074–83
   PubMed Web of Science ®Google Scholar
• Li Y, Cui M, Gao S. Efficacy of remifemin for control of climacteric symptoms. Prog Obstet Gynecol 2011;20:462–5
   Google Scholar
• Jiang K, Jin Y, Huang L, Feng S, Hou X, Du B. Black cohosh improves objective sleep in postmenopausal women with sleep disturbance. Climacteric 2015;18:559–67
   PubMed Web of Science ®Google Scholar
• Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J, Wernecke KD. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107:247–55
   PubMed Web of Science ®Google Scholar
• Nappi RE, Malavasi B, Brundu B, Facchinetti F. Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol 2005;20:30–5
   PubMed Web of Science ®Google Scholar
• Bai W, Henneicke-von Zepelin HH, Wang S, Zheng S, Liu J, Zhang Z. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas 2007;58:31–41
   PubMed Web of Science ®Google Scholar
• Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment-results of a large-scale, controlled, observational study. Maturitas 2007;57:405–14
   PubMed Web of Science ®Google Scholar
• Anampa J, Makower D, Sparano JA. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Med 2015;13:195
   PubMed Web of Science ®Google Scholar
• Schneider AP, 2nd, Zainer CM, Kubat CK, Mullen NK, Windisch AK. The breast cancer epidemic: 10 facts. Linacre Q 2014;81:244–77
   PubMedGoogle Scholar
• Leong SP, Shen ZZ, Liu TJ, et al. Is breast cancer the same disease in Asian and Western countries? World J Surg 2010;34:2308–24
   PubMed Web of Science ®Google Scholar
• Fan L, Strasser-Weippl K, Li J-J, et al. Breast cancer in China. Lancet Oncol 2014;15:e279–e89
   PubMed Web of Science ®Google Scholar
• Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739–45
   PubMed Web of Science ®Google Scholar
• Rostock M, Fischer J, Mumm A, Stammwitz U, Saller R, Bartsch HH. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints – a prospective observational study. Gyneco Endocrinol 2011;27:844–8
   PubMed Web of Science ®Google Scholar
• Pockaj BA, Loprinzi CL, Sloan JA, et al. Pilot evaluation of black cohosh for the treatment of hot flashes in women. Cancer Invest 2004;22:515–21
   PubMed Web of Science ®Google Scholar
• Wu X, Remifemin improve gynecological malignant tumor postoperative patients of menopause syndrome for the clinical research. Dalian Medical University: Master Degree Thesis; 2011.
   Google Scholar
• Henneicke-von Zepelin HH, Meden H, Kostev K, Schröder-Bernhardi D, Stammwitz U, Becher H. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. Int J Clin Pharmacol Ther 2007;45:143–54
   PubMed Web of Science ®Google Scholar
• Fischer J. Cimicifuga racemosa Extrakt (Remifemin®) bei Mamma-Ca-Patientinnen mit klimakterischen Beschwerden unter hormontherapeutischer Behandlung mit Tamoxifen – eine Anwendungsbeobachtung: Albert-Ludwigs-Universität; 2006.
   Google Scholar
• Huang X. The clinical research of Black cohosh extract in breast cancer patients with climacteric complaints 2011.
   Google Scholar
• Henneicke-von Zepelin H-H, Meden H, Kostev K, Schröder-Bernhardi D, Dietlein G, Friede M. Pharmakoepidemiologische Kohortenstudie zur Anwendung von Remifemin/Remifemin plus bei Patientinnen mit Mammakarzinom, einschließlich Hormonrezeptor-positiver Tumore. Interner Bericht Studiencode SB-FEM 1400. 2005.
   Google Scholar
• Hirschberg AL, Edlund M, Svane G, Azavedo E, Skoog L, von SB. An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women. Menopause 2007;14:89–96
   PubMed Web of Science ®Google Scholar
• Lundström E, Hirschberg AL, Soderqvist G. Digitized assessment of mammographic breast density – effects of continuous combined hormone therapy, tibolone and black cohosh compared to placebo. Maturitas 2011;70:361–4
   PubMed Web of Science ®Google Scholar
• Li W, Sun N-X, Chen X, Lang D-F, Jin Z-J. Cimicifuga racemosa for treatment of menopausal symptoms in patients with early endometrial cancer after operation. Acad J Second Mil Med Univ 2012;33:562–4
   Google Scholar
• Liske E, Hänggi W, Henneicke-von Zepelin H-H, Boblitz N, Wüstenberg P, Rahlfs VW. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Womens Health Gend Based Med 2002;11:163–74
   PubMedGoogle Scholar
• Sun N-x, Jin Z-j, Jia X-f, Li W. Black cohosh improves vaginal atrophy in postmenopausal women. Acad J Second Mil Med Univ 2012;32:339–41
   Google Scholar
• Garcia-Perez MA, Pineda B, Hermenegildo C, Tarin JJ, Cano A. Isopropanolic Cimicifuga racemosa is favorable on bone markers but neutral on an osteoblastic cell line. Fertil Steril 2009;91:1347–50
   PubMed Web of Science ®Google Scholar
• Nesselhut T, Liske E, editors. Pharmacological measures in postmenopausal women with an isopropanolic aqueous extract of Cimicifugae racemosae rhizoma. 10th Annual Meeting of the North American Menopause Society (NAMS); 1999: Menopause.
   Google Scholar
• Chen J, Gao H, Li Q, Cong J, Wu J, Pu D. Efficacy and safety of remifemin on peri-menopausal symptoms induced by post-operative GnRH-a therapy for endometriosis: a randomized study versus tibolone. Med Sci Monit 2014;20:1950–7
   PubMed Web of Science ®Google Scholar
• Reame NE, Lukacs JL, Padmanabhan V, Eyvazzadeh AD, Smith YR, Zubieta JK. Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause 2008;15:832–40
   PubMed Web of Science ®Google Scholar
• Obi N, Chang-Claude J, Berger J, et al. The use of herbal preparations to alleviate climacteric disorders and risk of postmenopausal breast cancer in a German case-control study. Cancer Epidemiol Biomarkers Prev 2009;18:2207–13
   PubMed Web of Science ®Google Scholar
• Rebbeck TR, Troxel AB, Norman S, et al. A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer 2007;120:1523–8
   PubMed Web of Science ®Google Scholar
• Zierau O, Bodinet C, Kolba S, Wulf M, Vollmer G. Antiestrogenic activities of Cimicifuga racemosa extracts. J Steroid Biochem Mol Biol 2002;80:125–30
   PubMed Web of Science ®Google Scholar
• Bodinet C, Freudenstein J. Influence of marketed herbal menopause preparations on MCF-7 cell proliferation. Menopause 2004;11:281–9
   PubMed Web of Science ®Google Scholar
• Omer-Adam MA, Zieg H, Bodinet C, Liske E. Quantification of characteristic marker substances and evaluation of their effects on MCF-7 cell proliferation. 7th Joint Meeting of GA, AFERP, ASP. 2008.
   Google Scholar
• Nesselhut T, Bodinet C, Schneider P, Freudenstein J. Inventors use of extract of Cimicifuga racemose; 2001.
   Google Scholar
• Bodinet C, Freudenstein J. Influence of Cimicifuga racemosa on the proliferation of estrogen receptor-positive human breast cancer cells. Breast Cancer Res Treat 2002;76:1–10
   PubMed Web of Science ®Google Scholar
• Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Evaluation of cell death caused by triterpene glycosides and phenolic substances from Cimicifuga racemosa extract in human MCF-7 breast cancer cells. Biol Pharm Bull 2004;27:1970–5
   PubMed Web of Science ®Google Scholar
• Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res Treat 2004;84:151–60
   PubMed Web of Science ®Google Scholar
• Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Inhibitory effect of an isopropanolic extract of black cohosh on the invasiveness of MDA-MB 231 human breast cancer cells. In Vivo 2007;21:349–55
   PubMed Web of Science ®Google Scholar
• Freudenstein J, Dasenbrock C, Nisslein T. Lack of promotion of estrogen-dependent mammary gland tumors in vivo by an isopropanolic Cimicifuga racemosa extract. Cancer Res 2002;62:3448–52
   PubMed Web of Science ®Google Scholar
• Nisslein T, Freudenstein J, editors. Prepubertal treatment with black cohosh attenuates pathogenicity in the DMBA rat model of mammary carcinoma. 10th world congress on the menopause; 2002 P06-08; Berlin: Climacteric.
   Google Scholar
• Nisslein T, Freudenstein J, editors. Synergistic effects of Black Cohosh and Tamoxifen in an animal model of mammary carcinoma. 6th European Congress on Menopause; 2003: Maturitas.
   Google Scholar
• Nißlein T, Freudenstein J. Coadministration of the aromatase inhibitor formestane and an isopropanolic extract of black cohosh in a rat model of chemically induced mammary carcinoma. Planta Med 2007;73:318–22
   PubMed Web of Science ®Google Scholar
• Davis VL, Jayo MJ, Ho A, et al. Black cohosh increases metastatic mammary cancer in transgenic mice expressing c-erbB2. Cancer Res 2008;68:8377–83
   PubMed Web of Science ®Google Scholar
• Stute P, Nisslein T, Gotte M, Kamischke A, Kiesel L, Klockenbusch W. Effects of black cohosh on estrogen biosynthesis in normal breast tissue in vitro. Maturitas 2007;57:382–91
   PubMed Web of Science ®Google Scholar
• Huang YX, Song L, Zhang X, Lun WW, Pan C, Huang YS. Clinical study of combined treatment of remifemin and paroxetine for perimenopausal depression. Zhonghua Yi Xue Za Zhi 2013;93:600–2
   PubMedGoogle Scholar
• Xi S, Liske E, Wang S, et al. Effect of isopropanolic Cimicifuga racemosa extract on uterine fibroids in comparison with tibolone among patients of a recent randomized, double blind, parallel-controlled study in Chinese women with menopausal symptoms. Evid Based Complement Alternat Med 2014;2014:1.
   Google Scholar
• Liske E. Phytokombination lindert psychovegetative Leiden. [Phytocombination alleviates psychovegatative disorders]. TW Gynäkologie 1997;10:172–5
   Google Scholar
• Schmidt M, Polasek W, Käufeler R. Wirksamkeit und Sicherheit von Traubensilberkerze (Cimicifuga racemosa, Cimifemin®) bei Menopausebeschwerden: Therapiebeobachtung unter Praxisbedingungen. J Für Menopause 2005;1:27–32
   Google Scholar
• Vermes G, Banhidy F, Acs N. The effects of remifemin on subjective symptoms of menopause. Adv Ther 2005;22:148–54
   PubMed Web of Science ®Google Scholar
• Arriaza Peso E, del Carmen Arévalo Páez M, Ángeles Grandas Alonso M, Olleros Izard T. Eficacia de Cimicifuga racemosa para el tratamiento de la clínica vasomotora y psíquica en pacientes menopáusicas. [Efficacy of Cimicifuga racemosa in the treatment of vasomotor and psychic symptoms in menopausal patients]. Progresos de Obstetricia y Ginecología 2008;51:20–7
   Google Scholar
• Julia Molla MD, Garcia-Sanchez Y, Romeu Sarri A, Perez-Lopez FR. Cimicifuga racemosa treatment and health related quality of life in post-menopausal Spanish women. Gynecol Endocrinol 2009;25:21–6
   PubMed Web of Science ®Google Scholar
• Arold G, Donath F, Maurer A, et al. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract. Planta Med 2005;71:331–7
   PubMed Web of Science ®Google Scholar
• European Medicines Agency (EMA), Committee for medicinal products for human use (CHMP). Guideline on clinical investigation of medicinal products for hormone replacement therapy of oestrogen deficiency symptoms in postmenopausal women. 2005.
   Google Scholar
• FDA. Guidance for Industry Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms — Recommendations for Clinical Evaluation. 2003.
   Google Scholar
• Beer A-M. Update Cimicifuga racemosa – neue Erkenntnisse aus Wissenschaft und Forschung: Differenzierte Evidenz für Wirksamkeit und Sicherheit von Traubensilberkerzen-Arzneimitteln zur Behandlung klimakterischer Beschwerden. J Gynäkol Endokrinol 2014;24:6–10
   Google Scholar
• Beer A-M. Cimicifuga in den Wechseljahren: Gibt es Risiken? MMW – Fortschritte Der Medizin 2013;155:22
   PubMedGoogle Scholar
• Hernández Muñoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas 2003;44:S59–S65
   PubMed Web of Science ®Google Scholar
• Lehmann-Willenbrock E, Riedel HH. Klinische und endokrinologische Untersuchungen zur Therapie ovarieller Ausfallerscheinungen nach Hysterektomie unter Belassung der Adnexe. Zent bl Gynäkol 1988;110:611–18
   PubMedGoogle Scholar
• Einbond LS, Wen-Cai Y, He K, et al. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine 2008;15:504–11
   PubMed Web of Science ®Google Scholar
• Nisslein T, Freudenstein J, editors. Long term treatment of uterine prone Dark Agouti rats with a standardized isopropanolic extract of Cimicifuga racemosa. 51st Annual Congress of the Society for Medicinal Plant Research; 2003; Kiel, Germany.
   Google Scholar
• Nisslein T, Freudenstein J. Concomitant administration of an isopropanolic extract of black cohosh and tamoxifen in the in vivo tumor model of implanted RUCA-I rat endometrial adenocarcinoma cells. Toxicol Lett 2004;150:271–5
   PubMed Web of Science ®Google Scholar
• Ikink GJ, Boer M, Bakker ERM, et al. Insertional mutagenesis in a HER2-positive breast cancer model reveals ERAS as a driver of cancer and therapy resistance. Oncogene 2018;37:1594–609
   PubMed Web of Science ®Google Scholar
• Paplomata EO´, Regan R. The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers. Ther Adv Med Oncol 2014;6:154–66
   PubMed Web of Science ®Google Scholar
• Ji L, Zhong B, Jiang X, et al. Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways. Oncotarget 2017;8:112498–515
   PubMedGoogle Scholar
• Yue GG, Xie S, Lee JK, et al. New potential beneficial effects of actein, a triterpene glycoside isolated from Cimicifuga species, in breast cancer treatment. Sci Rep 2016;6:35263
   PubMed Web of Science ®Google Scholar
• Moser C, Vickers SP, Brammer R, Cheetham SC, Drewe J. Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice. Phytomedicine 2014;21:1382–9
   PubMed Web of Science ®Google Scholar
• Moi LL, Flageng MH, Gjerde J, et al. Steroid receptor coactivators, HER-2 and HER-3 expression is stimulated by tamoxifen treatment in DMBA-induced breast cancer. BMC Cancer 2012;12:247
   PubMed Web of Science ®Google Scholar
• Kennelly EJ, Baggett S, Nuntanakorn P, et al. Analysis of thirteen populations of black cohosh for formononetin. Phytomedicine 2002;9:461–7
   PubMed Web of Science ®Google Scholar
• Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol 2003;84:259–68
   PubMed Web of Science ®Google Scholar
• Kostev K. Re-evaluations regarding the REMIFEMIN-study (2004) "study code: SB-FEM1400". IMS® Disease Analyzer 2009.
   Google Scholar
• Community Herbal Monograph on Hypericum perforatum L., Herba. Well-established medicinal use [Internet]. 2009. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2010/01/WC500059145.pdf
   Google Scholar
• Fachinformation (Summary of Product Characteristics). Remifemin plus Johanniskraut. Aug. 2015.
   Google Scholar
• Mueller SC, Majcher-Peszynska J, Uehleke B, et al. The extent of induction of CYP3A by St. John's wort varies among products and is linked to hyperforin dose. Eur J Clin Pharmacol 2006;62:29–36
   PubMed Web of Science ®Google Scholar
• Madabushi R, Frank B, Drewelow B, Derendorf H, Butterweck V. Hyperforin in St. John's wort drug interactions. Eur J Clin Pharmacol 2006;62:225–33
   PubMed Web of Science ®Google Scholar
• Stargrove MB, Treasure J, McKee DL, Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies. Mosby Elsevier: St. Louis, Missouri, United States of America 2008:140–59.
   Google Scholar
• Wurglics M, Westerhoff K, Kaunzinger A, et al. Comparison of German St. John's wort products according to hyperforin and total hypericin content. J Am Pharm Assoc (Wash) 2001;41:560–6
   PubMedGoogle Scholar
• Mueller SC, Uehleke B, Woehling H, et al. Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther 2004;75:546–57
   PubMed Web of Science ®Google Scholar
• Mueller SC, Majcher-Peszynska J, Mundkowski RG, et al. No clinically relevant CYP3A induction after St. John´s wort with low hyperforin content in healthy volunteers. Eur J Clin Pharmacol 2009;65:81–7
   PubMed Web of Science ®Google Scholar
• Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol 2006;62:512–26
   PubMed Web of Science ®Google Scholar
• Musterfachinformation Tamoxifencitrat [Internet]. 2015 [cited 04.07.2017]. Available from: https://sunset-clause.dimdi.de/muster/O9b59fc22f0a34cf7a8fb53b59eee5096.pdf
   Google Scholar
• ter Heine R, Binkhorst L, de Graan AJM, et al. Population pharmacokinetic modelling to assess the impact of CYP2D6 and CYP3A metabolic phenotypes on the pharmacokinetics of tamoxifen and endoxifen. Br J Clin Pharmacol 2014;78:572–86
   PubMed Web of Science ®Google Scholar
• Tan SH, Lee S-C, Goh B-C, Wong J. Pharmacogenetics in breast cancer therapy. Clin Cancer Res 2008;14:8027–41
   PubMed Web of Science ®Google Scholar
• Klein DJ, Thorn CF, Desta Z, Flockhart DA, Altman RB, Klein TE. PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenet Genomics 2013;23:643–7
   PubMed Web of Science ®Google Scholar
• Cronin-Fenton DP, Damkier P, Lash TL. Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol 2014;10:107–22
   PubMed Web of Science ®Google Scholar
• Neven P, Jongen L, Lintermans A, et al. Tamoxifen metabolism and efficacy in breast cancer: a prospective multicenter trial. Clin Cancer Res 2018;24:2312–18
   PubMed Web of Science ®Google Scholar
• Kuypers DR, Verleden G, Naesens M, Vanrenterghem Y. Drug interaction between mycophenolate mofetil and rifampin: possible induction of uridine diphosphate-glucuronosyltransferase. Clin Pharmacol Ther 2005;78:81–8
   PubMed Web of Science ®Google Scholar
• Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). Musterfachinformation Anastrozol. 18.04.2018 ed2018.
   Google Scholar
• Linardi A, Damiani D, Longui CA. The use of aromatase inhibitors in boys with short stature: what to know before prescribing? Arch Endocrinol Metab 2017;61:391–7
   PubMed Web of Science ®Google Scholar
• Kamdem LK, Liu Y, Stearns V, et al. In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol 2010;70:854–69
   PubMed Web of Science ®Google Scholar
• Fachinformation (Summary of Product Characteristics). Femara 2.5 mg. Oct. 2017.
   Google Scholar
• Murai K, Yamazaki H, Nakagawa K, Kawai R, Kamataki T. Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes. Xenobiotica 2009;39:795–802
   PubMed Web of Science ®Google Scholar
• Desta Z, Kreutz Y, Nguyen AT, et al. Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age. Clin Pharmacol Ther 2011;90:693–700
   PubMed Web of Science ®Google Scholar
• Landry KK, David FA, Zeruesenay D. 17-Hydroexemestane: a potent inhibitor of CYP19 (aromatase) and substrate of CYP3A. J Drug Metabolism Toxicol 2014;5:2.
   Google Scholar
• Kamdem LK, Flockhart DA, Desta Z. In vitro cytochrome P450-mediated metabolism of exemestane. Drug Metab Dispos 2011;39:98–105
   PubMed Web of Science ®Google Scholar
• Fachinformation (Summary of Product Characteristics). Aromasin Dec. 2017.
   Google Scholar
• Hertz DL, Kidwell KM, Seewald NJ, et al. Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in postmenopausal patients with breast cancer. Pharmacogenomics J 2017;17:521–7
   PubMed Web of Science ®Google Scholar