The implications of genetic variation for the pharmacokinetics and pharmacodynamics of aromatase inhibitors

References

• Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386.
   PubMed Web of Science ®Google Scholar
• Gucalp A, Gupta GP, Pilewskie ML, et al. Advances in managing breast cancer: a clinical update. F1000Prime Rep. 2014;6:66.
   PubMedGoogle Scholar
• Parise CA, Caggiano V. Breast cancer survival defined by the ER/PR/HER2 subtypes and a surrogate classification according to tumor grade and immunohistochemical biomarkers. J Cancer Epidemiol. 2014;2014:469251.
   PubMedGoogle Scholar
• Jordan VC. Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov. 2003;2(3):205–213.
   PubMed Web of Science ®Google Scholar
• Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–784.
   PubMed Web of Science ®Google Scholar
• Braithwaite RS, Chlebowski RT, Lau J, et al. Meta-analysis of vascular and neoplastic events associated with tamoxifen. J Gen Intern Med. 2003;18(11):937–947.
   PubMed Web of Science ®Google Scholar
• Wysowski DK, Honig SF, Beitz J. Uterine sarcoma associated with tamoxifen use. N Engl J Med. 2002;346(23):1832–1833.
   PubMed Web of Science ®Google Scholar
• Ring A, Dowsett M. Mechanisms of tamoxifen resistance. Endocr Relat Cancer. 2004;11(4):643–658.
   PubMed Web of Science ®Google Scholar
• Chumsri S, Howes T, Bao T, et al. Aromatase, aromatase inhibitors, and breast cancer. J Steroid Biochem Mol Biol. 2011;125(1–2):13–22.
   PubMed Web of Science ®Google Scholar
• Falkson CI, Falkson HC. A randomised study of CGS 16949A (fadrozole) versus tamoxifen in previously untreated postmenopausal patients with metastatic breast cancer. Ann Oncol. 1996;7(5):465–469.
   PubMed Web of Science ®Google Scholar
• Thurlimann B, Beretta K, Bacchi M, et al. First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer. Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88. Ann Oncol. 1996;7(5):471–479.
   PubMed Web of Science ®Google Scholar
• Buzdar AU, Smith R, Vogel C, et al. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996;77(12):2503–2513.
   PubMed Web of Science ®Google Scholar
• Hausler A, Monnet G, Borer C, et al. Evidence that corticosterone is not an obligatory intermediate in aldosterone biosynthesis in the rat adrenal. J Steroid Biochem. 1989;34(1–6):567–570.
   PubMedGoogle Scholar
• Lamberts SW, Bruining HA, Marzouk H, et al. The new aromatase inhibitor CGS-16949A suppresses aldosterone and cortisol production by human adrenal cells in vitro. J Clin Endocrinol Metab. 1989;69(4):896–901.
   PubMed Web of Science ®Google Scholar
• Hong Y, Chen S. Aromatase inhibitors: structural features and biochemical characterization. Ann N Y Acad Sci. 2006;1089:237–251.
   PubMed Web of Science ®Google Scholar
• Bonneterre J, Buzdar A, Nabholtz JM, et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer. 2001;92(9):2247–2258.
   PubMed Web of Science ®Google Scholar
• Thurlimann B, Hess D, Koberle D, et al. Anastrozole (‘Arimidex’) versus tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer: results of the double-blind cross-over SAKK trial 21/95--a sub-study of the TARGET (Tamoxifen or ‘Arimidex’ Randomized Group Efficacy and Tolerability) trial. Breast Cancer Res Treat. 2004;85(3):247–254.
   PubMed Web of Science ®Google Scholar
• Smith IE. Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. J Steroid Biochem Mol Biol. 2003;86(3–5):289–293.
   PubMed Web of Science ®Google Scholar
• Mouridsen H, Gershanovich M, Sun Y, et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol. 2001;19(10):2596–2606.
   PubMed Web of Science ®Google Scholar
• Paridaens R, Dirix L, Lohrisch C, et al. Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Ann Oncol. 2003;14(9):1391–1398.
   PubMed Web of Science ®Google Scholar
• Coombes RC, Harper-Wynne C, Dowsett M. Aromatase inhibitors and their use in the sequential setting. Endocr Relat Cancer. 1999;6(2):259–263.
   PubMed Web of Science ®Google Scholar
• Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med. 2003;348(24):2431–2442.
   PubMed Web of Science ®Google Scholar
• Brueggemeier RW, Hackett JC, Diaz-Cruz ES. Aromatase inhibitors in the treatment of breast cancer. Endocr Rev. 2005;26(3):331–345.
   PubMed Web of Science ®Google Scholar
• Forbes JF, Cuzick J, Buzdar A, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9(1):45–53.
   PubMed Web of Science ®Google Scholar
• Regan MM, Neven P, Giobbie-Hurder A, et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol. 2011;12(12):1101–1108.
   PubMed Web of Science ®Google Scholar
• Smith IE, Dowsett M, Ebbs SR, et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol. 2005;23(22):5108–5116.
   PubMed Web of Science ®Google Scholar
• Cataliotti L, Buzdar AU, Noguchi S, et al. Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative “Arimidex” Compared to Tamoxifen (PROACT) trial. Cancer. 2006;106(10):2095–2103.
   PubMed Web of Science ®Google Scholar
• Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365(9453):60–62.
   PubMed Web of Science ®Google Scholar
• Coates AS, Keshaviah A, Thurlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007;25(5):486–492.
   PubMed Web of Science ®Google Scholar
• Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007;369(9561):559–570.
   PubMed Web of Science ®Google Scholar
• Eiermann W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol. 2001;12(11):1527–1532.
   PubMed Web of Science ®Google Scholar
• Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol. 2001;19(18):3808–3816.
   PubMed Web of Science ®Google Scholar
• Miller WR, Larionov A, Renshaw L, et al. Gene expression profiles differentiating between breast cancers clinically responsive or resistant to letrozole. J Clin Oncol. 2009;27(9):1382–1387.
   PubMed Web of Science ®Google Scholar
• Gotay C, Dunn J. Adherence to long-term adjuvant hormonal therapy for breast cancer. Expert Rev Pharmacoecon Outcomes Res. 2011;11(6):709–715.
   PubMed Web of Science ®Google Scholar
• Werk AN, Cascorbi I. Functional gene variants of CYP3A4. Clin Pharmacol Ther. 2014;96(3):340–348.
   PubMed Web of Science ®Google Scholar
• Perera MA. The missing linkage: what pharmacogenetic associations are left to find in CYP3A? Expert Opin Drug Metab Toxicol. 2010;6(1):17–28.
   PubMed Web of Science ®Google Scholar
• Dowsett M, Cuzick J, Howell A, et al. Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the ‘Arimidex and tamoxifen alone or in combination’ (ATAC) trial. Br J Cancer. 2001;85(3):317–324.
   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(6):854–869.
   PubMed Web of Science ®Google Scholar
• Lazarus P, Sun D. Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen and aromatase inhibitors. Drug Metab Rev. 2010;42(1):182–194.
   PubMed Web of Science ®Google Scholar
• Jakoby WB, Ziegler DM. The enzymes of detoxication. J Biol Chem. 1990;265(34):20715–20718.
   PubMed Web of Science ®Google Scholar
• Edavana VK, Dhakal IB, Williams S, et al. Potential role of UGT1A4 promoter SNPs in anastrozole pharmacogenomics. Drug Metab Dispos. 2013;41(4):870–877.
   PubMed Web of Science ®Google Scholar
• Altshuler DM, Gibbs RA, Peltonen L, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467(7311):52–58.
   PubMed Web of Science ®Google Scholar
• Auton A, Brooks LD, Durbin RM, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.
   PubMed Web of Science ®Google Scholar
• Murai K, Yamazaki H, Nakagawa K, et al. Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes. Xenobiotica. 2009;39(11):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(5):693–700.
   PubMed Web of Science ®Google Scholar
• Kamdem LK, Flockhart DA, Desta Z. In vitro cytochrome P450-mediated metabolism of exemestane. Drug Metab Dispos. 2011;39(1):98–105.
   PubMed Web of Science ®Google Scholar
• Sun D, Chen G, Dellinger RW, et al. Characterization of 17-dihydroexemestane glucuronidation: potential role of the UGT2B17 deletion in exemestane pharmacogenetics. Pharmacogenet Genomics. 2010;20(10):575–585.
   PubMed Web of Science ®Google Scholar
• Chen SM, Atchley DH, Murphy MA, et al. Impact of UGT2B17 gene deletion on the pharmacokinetics of 17-hydroexemestane in healthy volunteers. J Clin Pharmacol. 2015 Nov 26. doi: 10.1002/jcph.673. [Epub ahead of print]
   Web of Science ®Google Scholar
• Wilson W 3rd, Pardo-Manuel de Villena F, Lyn-Cook BD, et al. Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics. 2004;84(4):707–714.
   PubMed Web of Science ®Google Scholar
• Jakobsson J, Ekstrom L, Inotsume N, et al. Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. J Clin Endocrinol Metab. 2006;91(2):687–693.
   PubMed Web of Science ®Google Scholar
• Ma CX, Adjei AA, Salavaggione OE, et al. Human aromatase: gene resequencing and functional genomics. Cancer Res. 2005;65(23):11071–11082.
   PubMed Web of Science ®Google Scholar
• Wang L, Ellsworth KA, Moon I, et al. Functional genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to neoadjuvant therapy with aromatase inhibitors. Cancer Res. 2010;70(1):319–328.
   PubMed Web of Science ®Google Scholar
• Ghimenti C, Mello-Grand M, Grosso E, et al. Regulation of aromatase expression in breast cancer treated with anastrozole neoadjuvant therapy. Exp Ther Med. 2013;5(3):902–906.
   PubMed Web of Science ®Google Scholar
• Garcia-Casado Z, Guerrero-Zotano A, Llombart-Cussac A, et al. A polymorphism at the 3’-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole. BMC Cancer. 2010;10:36.
   PubMed Web of Science ®Google Scholar
• Colomer R, Monzo M, Tusquets I, et al. A single-nucleotide polymorphism in the aromatase gene is associated with the efficacy of the aromatase inhibitor letrozole in advanced breast carcinoma. Clin Cancer Res. 2008;14(3):811–816.
   PubMed Web of Science ®Google Scholar
• Liu L, Bai YX, Zhou JH, et al. A polymorphism at the 3-UTR region of the aromatase gene is associated with the efficacy of the aromatase inhibitor, anastrozole, in metastatic breast carcinoma. Int J Mol Sci. 2013;14(9):18973–18988.
   PubMed Web of Science ®Google Scholar
• Lunardi G, Piccioli P, Bruzzi P, et al. Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus in postmenopausal women with early breast cancer treated with letrozole. Breast Cancer Res Treat. 2013;137(1):167–174.
   PubMed Web of Science ®Google Scholar
• Park IH, Lee YS, Lee KS, et al. Single nucleotide polymorphisms of CYP19A1 predict clinical outcomes and adverse events associated with letrozole in patients with metastatic breast cancer. Cancer Chemother Pharmacol. 2011;68(5):1263–1271.
   PubMed Web of Science ®Google Scholar
• Ferraldeschi R, Arnedos M, Hadfield KD, et al. Polymorphisms of CYP19A1 and response to aromatase inhibitors in metastatic breast cancer patients. Breast Cancer Res Treat. 2012;133(3):1191–1198.
   PubMed Web of Science ®Google Scholar
• Rumiato E, Brunello A, Ahcene-Djaballah S, et al. Predictive markers in elderly patients with estrogen receptor-positive breast cancer treated with aromatase inhibitors: an array-based pharmacogenetic study. Pharmacogenomics J. 2015. Oct 27. doi:10.1038/tpj.2015.73.
   Google Scholar
• Kim J, Han W, Moon HG, et al. Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res. 2012;14(4):R102.
   Google Scholar
• Li J, Humphreys K, Eriksson L, et al. Mammographic density reduction is a prognostic marker of response to adjuvant tamoxifen therapy in postmenopausal patients with breast cancer. J Clin Oncol. 2013;31(18):2249–2256.
   PubMed Web of Science ®Google Scholar
• Henry NL, Chan HP, Dantzer J, et al. Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects. Br J Cancer. 2013;109(9):2331–2339.
   PubMed Web of Science ®Google Scholar
• Crew KD, Greenlee H, Capodice J, et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol. 2007;25(25):3877–3883.
   PubMed Web of Science ®Google Scholar
• Henry NL, Giles JT, Ang D, et al. Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat. 2008;111(2):365–372.
   PubMed Web of Science ®Google Scholar
• Servitja S, Nogues X, Prieto-Alhambra D, et al. Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer. Breast. 2012;21(1):95–101.
   PubMed Web of Science ®Google Scholar
• Gonnelli S, Petrioli R. Aromatase inhibitors, efficacy and metabolic risk in the treatment of postmenopausal women with early breast cancer. Clin Interv Aging. 2008;3(4):647–657.
   PubMed Web of Science ®Google Scholar
• Markopoulos C, Polychronis A, Zobolas V, et al. The effect of exemestane on the lipidemic profile of postmenopausal early breast cancer patients: preliminary results of the TEAM Greek sub-study. Breast Cancer Res Treat. 2005;93(1):61–66.
   PubMed Web of Science ®Google Scholar
• Haiman CA, Dossus L, Setiawan VW, et al. Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women. Cancer Res. 2007;67(5):1893–1897.
   PubMed Web of Science ®Google Scholar
• Cai H, Shu XO, Egan KM, et al. Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women. Pharmacogenet Genomics. 2008;18(8):657–664.
   PubMed Web of Science ®Google Scholar
• Masi L, Becherini L, Gennari L, et al. Polymorphism of the aromatase gene in postmenopausal Italian women: distribution and correlation with bone mass and fracture risk. J Clin Endocrinol Metab. 2001;86(5):2263–2269.
   PubMed Web of Science ®Google Scholar
• Dick IM, Devine A, Prince RL. Association of an aromatase TTTA repeat polymorphism with circulating estrogen, bone structure, and biochemistry in older women. Am J Physiol Endocrinol Metab. 2005;288(5):E989–E995.
   Google Scholar
• Napoli N, Rastelli A, Ma C, et al. Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with aromatase inhibitor associated bone loss in women with ER + breast cancer. Bone. 2013;55(2):309–314.
   PubMed Web of Science ®Google Scholar
• Oesterreich S, Henry NL, Kidwell KM, et al. Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover. Breast Cancer Res Treat. 2015;154(2):263–273.
   PubMed Web of Science ®Google Scholar
• Santa-Maria CA, Blackford AL, Nguyen AT, et al. Association of variants in candidate genes with lipid profiles in women with early breast cancer on adjuvant aromatase inhibitor therapy. Clin Cancer Res. 2016.;22:1395–1402.
   PubMed Web of Science ®Google Scholar
• Lee MJ, Wu Y, Fried SK. Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med. 2013;34(1):1–11.
   PubMed Web of Science ®Google Scholar
• Napoli N, Rastelli A, Ma C, et al. Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with body composition changes in women on aromatase inhibitors for ER (+) breast cancer. Pharmacogenet Genomics. 2015;25(8):377–381.
   PubMed Web of Science ®Google Scholar
• Fontein DB, Houtsma D, Nortier JW, et al. Germline variants in the CYP19A1 gene are related to specific adverse events in aromatase inhibitor users: a substudy of Dutch patients in the TEAM trial. Breast Cancer Res Treat. 2014;144(3):599–606.
   PubMed Web of Science ®Google Scholar
• Chlebowski RT. Aromatase inhibitor-associated arthralgias. J Clin Oncol. 2009;27(30):4932–4934.
   PubMed Web of Science ®Google Scholar
• Coleman RE, Bolten WW, Lansdown M, et al. Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev. 2008;34(3):275–282.
   PubMed Web of Science ®Google Scholar
• Mao JJ, Su HI, Feng R, et al. Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors. Breast Cancer Res. 2011;13(1):R8.
   PubMed Web of Science ®Google Scholar
• Bord S, Horner A, Beavan S, et al. Estrogen receptors alpha and beta are differentially expressed in developing human bone. J Clin Endocrinol Metab. 2001;86(5):2309–2314.
   PubMed Web of Science ®Google Scholar
• Braidman IP, Hainey L, Batra G, et al. Localization of estrogen receptor beta protein expression in adult human bone. J Bone Miner Res. 2001;16(2):214–220.
   PubMed Web of Science ®Google Scholar
• Del Re M, Michelucci A, Simi P, et al. Pharmacogenetics of anti-estrogen treatment of breast cancer. Cancer Treat Rev. 2012;38(5):442–450.
   PubMed Web of Science ®Google Scholar
• Gennari L, Merlotti D, De Paola V, et al. Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol. 2005;161(4):307–320.
   PubMed Web of Science ®Google Scholar
• Wang J, Lu K, Song Y, et al. Indications of clinical and genetic predictors for aromatase inhibitors related musculoskeletal adverse events in Chinese Han women with breast cancer. PLoS One. 2013;8(7):e68798.
   PubMed Web of Science ®Google Scholar
• Maruyama H, Toji H, Harrington CR, et al. Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease. Arch Neurol. 2000;57(2):236–240.
   PubMedGoogle Scholar
• Koukouras D, Marioli DJ, Papadopoulos K, et al. Association of estrogen receptor alpha (ERalpha) gene polymorphisms with endometrial thickness and lipid profile in women with breast cancer treated with aromatase inhibitors. Gynecol Endocrinol. 2012;28(11):859–862.
   PubMed Web of Science ®Google Scholar
• Henry NL, Skaar TC, Dantzer J, et al. Genetic associations with toxicity-related discontinuation of aromatase inhibitor therapy for breast cancer. Breast Cancer Res Treat. 2013;138(3):807–816.
   PubMed Web of Science ®Google Scholar
• Anghel A, Raica M, Narita D, et al. Estrogen receptor alpha polymorphisms: correlation with clinicopathological parameters in breast cancer. Neoplasma. 2010;57(4):306–315.
   PubMed Web of Science ®Google Scholar
• Leyland-Jones B, Gray KP, Abramovitz M, et al. ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer. Breast Cancer Res Treat. 2015;154(3):543–555.
   PubMed Web of Science ®Google Scholar
• Mosa A, Neunzig J, Gerber A, et al. 2β- and 16β-hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation. J Steroid Biochem Mol Biol. 2015;150:1–10.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Sanz M, Garcia-Giralt N, Prieto-Alhambra D, et al. CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss. J Mol Endocrinol. 2015;55(1):69–79.
   PubMed Web of Science ®Google Scholar
• Nogues X, Servitja S, Pena MJ, et al. Vitamin D deficiency and bone mineral density in postmenopausal women receiving aromatase inhibitors for early breast cancer. Maturitas. 2010;66(3):291–297.
   PubMed Web of Science ®Google Scholar
• Prieto-Alhambra D, Javaid MK, Servitja S, et al. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Res Treat. 2011;125(3):869–878.
   PubMed Web of Science ®Google Scholar
• Waltman NL, Ott CD, Twiss JJ, et al. Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy. Cancer Nurs. 2009;32(2):143–150.
   PubMed Web of Science ®Google Scholar
• Takeyama K, Kitanaka S, Sato T, et al. 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science. 1997;277(5333):1827–1830.
   PubMed Web of Science ®Google Scholar
• Baldock PA, Thomas GP, Hodge JM, et al. Vitamin D action and regulation of bone remodeling: suppression of osteoclastogenesis by the mature osteoblast. J Bone Miner Res. 2006;21(10):1618–1626.
   PubMed Web of Science ®Google Scholar
• Dhir V, Ivison HE, Krone N, et al. Differential inhibition of CYP17A1 and CYP21A2 activities by the P450 oxidoreductase mutant A287P. Mol Endocrinol. 2007;21(8):1958–1968.
   PubMed Web of Science ®Google Scholar
• Gilep AA, Sushko TA, Usanov SA. At the crossroads of steroid hormone biosynthesis: the role, substrate specificity and evolutionary development of CYP17. Biochim Biophys Acta. 2011;1814(1):200–209.
   PubMed Web of Science ®Google Scholar
• Mennenga SE, Koebele SV, Mousa AA, et al. Pharmacological blockade of the aromatase enzyme, but not the androgen receptor, reverses androstenedione-induced cognitive impairments in young surgically menopausal rats. Steroids. 2015;99(Pt A):16–25.
   PubMed Web of Science ®Google Scholar
• Garcia-Giralt N, Rodriguez-Sanz M, Prieto-Alhambra D, et al. Genetic determinants of aromatase inhibitor-related arthralgia: the B-ABLE cohort study. Breast Cancer Res Treat. 2013;140(2):385–395.
   PubMed Web of Science ®Google Scholar
• Arai H, Miyamoto KI, Yoshida M, et al. The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. J Bone Miner Res. 2001;16(7):1256–1264.
   PubMed Web of Science ®Google Scholar
• Baud’huin M, Duplomb L, Ruiz Velasco C, et al. Key roles of the OPG-RANK-RANKL system in bone oncology. Expert Rev Anticancer Ther. 2007;7(2):221–232.
   PubMed Web of Science ®Google Scholar
• Boyce BF, Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 2007;9(Suppl 1):S1.
   PubMed Web of Science ®Google Scholar
• Xiong J, O’Brien CA. Osteocyte RANKL: new insights into the control of bone remodeling. J Bone Miner Res. 2012;27(3):499–505.
   PubMed Web of Science ®Google Scholar
• Wright HL, McCarthy HS, Middleton J, et al. RANK, RANKL and osteoprotegerin in bone biology and disease. Curr Rev Musculoskelet Med. 2009;2(1):56–64.
   PubMedGoogle Scholar
• Wang J, Lu K, Song Y, et al. RANKL and OPG polymorphisms are associated with aromatase inhibitor-related musculoskeletal adverse events in Chinese Han breast cancer patients. PLoS One. 2015;10(7):e0133964.
   PubMed Web of Science ®Google Scholar
• Tan W, Wu H, Zhao J, et al. A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis. Arthritis Rheum. 2010;62(10):2864–2875.
   PubMed Web of Science ®Google Scholar
• Lintermans A, Van Asten K, Jongen L, et al. Genetic variant in the osteoprotegerin gene is associated with aromatase inhibitor-related musculoskeletal toxicity in breast cancer patients. Eur J Cancer. 2016;56:31–36.
   PubMed Web of Science ®Google Scholar
• Ingle JN, Schaid DJ, Goss PE, et al. Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. J Clin Oncol. 2010;28(31):4674–4682.
   PubMed Web of Science ®Google Scholar
• Liu M, Goss PE, Ingle JN, et al. Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics. Mol Endocrinol. 2014;28(10):1740–1751.
   PubMed Web of Science ®Google Scholar
• Evangelou E, Ioannidis JPA. Meta-analysis methods for genome-wide association studies and beyond. Nat Rev Genet. 2013;14(6):379–389.
   PubMed Web of Science ®Google Scholar
• Gomez A, Ingelman-Sundberg M. Pharmacoepigenetics: its role in interindividual differences in drug response. Clin Pharmacol Ther. 2009;85(4):426–430.
   PubMed Web of Science ®Google Scholar