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Pharmacogenomics of Breast Cancer

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Molecular Pathology of Breast Cancer

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Abstract

Pharmacogenomic markers may be able to identify subgroups of patients who will optimally benefit from a particular therapy, other patients who might derive little or no benefit, and/or individuals who are at elevated risk for serious adverse events. It is expected that these studies will enable optimization of risk-benefit ratios for therapeutic agents. In order to fully realize the potential of these markers, it is important to understand the biology underlying drug response. Full realization of the potential of this approach will require the integration of basic discoveries in drug development and pharmacogenomic variability, genomic and outcome data from phase I–III randomized clinical trials, and data on the effects of drugs and their interactions with genomic variants in large populations. In this Chapter, polymorphic genes that have been implicated in both ER-positive and ER-negative cancers will be discussed, as well as other genes that have been implicated through genome-wide association studies (GWAS) in breast cancer.

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References

  • Ahern TP, Christensen M, Cronin-Fenton DP et al (2010) Concordance of metabolic enzyme genotypes assayed from paraffin-embedded, formalin-fixed breast tumors and normal lymphatic tissue. Clin Epidemiol 2:241–246

    Article  PubMed  PubMed Central  Google Scholar 

  • Ahmad A, Shahabuddin S, Sheikh S et al (2010) Endoxifen, a new cornerstone of breast cancer therapy: demonstration of safety, tolerability, and systemic bioavailability in healthy human subjects. Clin Pharmacol Ther 88(6):814–817

    Article  CAS  PubMed  Google Scholar 

  • Almeida S, Hutz MH (2008) Estrogen receptor 1 gene polymorphisms in premenopausal women: interaction between genotype and smoking on lipid levels. Braz J Med Biol Res 41(10):872–876

    Article  CAS  PubMed  Google Scholar 

  • Baldwin RM, Owzar K, Zembutsu H et al (2012) A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. Clin Cancer Res 18(18):5099–5109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmann TK, Brasch-Andersen C, Green H et al (2011) Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer. Pharmacogenomics J 11(2):113–120

    Article  CAS  PubMed  Google Scholar 

  • Bonanni B, Macis D, Maisonneuve P et al. (2006) Polymorphism in the CYP2D6 tamoxifen-metabolizing gene influences clinical effect but not hot flashes: data from the Italian Tamoxifen Trial. J Clin Oncol 24(22):3708–3709; author reply 3709

    Google Scholar 

  • Borges S, Desta Z, Li L et al (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80(1):61–74

    Article  CAS  PubMed  Google Scholar 

  • Boyapati SM, Shu XO, Ruan ZX et al (2005) Polymorphisms in ER-alpha gene interact with estrogen receptor status in breast cancer survival. Clin Cancer Res 11(3):1093–1098

    CAS  PubMed  Google Scholar 

  • Brauch H, Murdter TE, Eichelbaum M, Schwab M (2009) Pharmacogenomics of tamoxifen therapy. Clin Chem 55(10):1770–1782

    Article  CAS  PubMed  Google Scholar 

  • Brauch H, Schroth W, Goetz MP et al (2013) Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters. J Clin Oncol 31(2):176–180

    Article  CAS  PubMed  Google Scholar 

  • Breast International Group 1-98 Collaborative G, Thurlimann B, Keshaviah A et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353(26):2747–2757

    Google Scholar 

  • Buzdar AU, Singletary SE, Theriault RL et al (1999) Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol 17(11):3412–3417

    CAS  PubMed  Google Scholar 

  • Cai Q, Shu XO, Jin F et al (2003) Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev 12(9):853–859

    CAS  PubMed  Google Scholar 

  • Cai Q, Kataoka N, Li C et al (2008) Haplotype analyses of CYP19A1 gene variants and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev 17(1):27–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang H, Rha SY, Jeung HC et al (2009) Association of the ABCB1 gene polymorphisms 2677G > T/A and 3435C > T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients. Ann Oncol 20(2):272–277

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Sakoda LC, Doherty JA et al (2008) Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai. China. Cancer Epidemiol Biomarkers Prev 17(12):3457–3466

    Article  CAS  PubMed  Google Scholar 

  • Clendenen T, Zeleniuch-Jacquotte A, Wirgin I et al (2013) Genetic variants in hormone-related genes and risk of breast cancer. PLoS ONE 8(7):e69367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coates AS, Keshaviah A, Thurlimann B et al (2007) 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 25(5):486–492

    Article  CAS  PubMed  Google Scholar 

  • Colleoni M, Giobbie-Hurder A, Regan MM et al (2011) Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. J Clin Oncol 29(9):1117–1124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colomer R, Monzo M, Tusquets I et al (2008) 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 14(3):811–816

    Article  CAS  PubMed  Google Scholar 

  • Crandall CJ, Sehl ME, Crawford SL et al (2009) Sex steroid metabolism polymorphisms and mammographic density in pre- and early perimenopausal women. Breast Cancer Res 11(4):R51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cronin-Fenton DP, Damkier P, Lash TL (2014) Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol 10(1):107–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuzick J, Sestak I, Cella D, Fallowfield L, Group AT (2008) Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol 9(12):1143–1148

    Article  CAS  Google Scholar 

  • Desta Z, Ward BA, Soukhova NV, Flockhart DA (2004) Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 310(3):1062–1075

    Article  CAS  PubMed  Google Scholar 

  • Dowsett M, Haynes BP (2003) Hormonal effects of aromatase inhibitors: focus on premenopausal effects and interaction with tamoxifen. J Steroid Biochem Mol Biol 86(3–5):255–263

    Article  CAS  PubMed  Google Scholar 

  • Dunning AM, Healey CS, Baynes C et al (2009) Association of ESR1 gene tagging SNPs with breast cancer risk. Hum Mol Genet 18(6):1131–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Early Breast Cancer Trialists’ Collaborative G, Davies C, Godwin J et al (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378(9793):771–784

    Google Scholar 

  • Enjuanes A, Garcia-Giralt N, Supervia A et al (2006) A new SNP in a negative regulatory region of the CYP19A1 gene is associated with lumbar spine BMD in postmenopausal women. Bone 38(5):738–743

    Article  CAS  PubMed  Google Scholar 

  • Fasching PA, Loehberg CR, Strissel PL et al (2008) Single nucleotide polymorphisms of the aromatase gene (CYP19A1), HER2/neu status, and prognosis in breast cancer patients. Breast Cancer Res Treat 112(1):89–98

    Article  CAS  PubMed  Google Scholar 

  • Fehrmann RS, Jansen RC, Veldink JH et al (2011) Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet 7(8):e1002197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferraldeschi R, Newman WG (2010) The impact of CYP2D6 genotyping on tamoxifen treatment. Pharmaceuticals 3(4):1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferraldeschi R, Arnedos M, Hadfield KD et al (2012) Polymorphisms of CYP19A1 and response to aromatase inhibitors in metastatic breast cancer patients. Breast Cancer Res Treat 133(3):1191–1198

    Article  CAS  PubMed  Google Scholar 

  • Fisher B, Dignam J, Bryant J et al (1996) Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 88(21):1529–1542

    Article  CAS  PubMed  Google Scholar 

  • Fontein DB, Houtsma D, Nortier JW et al (2014) 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 144(3):599–606

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Casado Z, Guerrero-Zotano A, Llombart-Cussac A et al (2010) 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 10:36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gennari L, Merlotti D, De Paola V et al (2005) Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol 161(4):307–320

    Article  CAS  PubMed  Google Scholar 

  • Gines J, Sabater E, Martorell C, Grau M, Monroy M, Casado MA (2011) Efficacy of taxanes as adjuvant treatment of breast cancer: a review and meta-analysis of randomised clinical trials. Clin Transl Oncol 13(7):485–498

    Article  CAS  PubMed  Google Scholar 

  • Gjerde J, Hauglid M, Breilid H, Lundgren S, Varhaug JE (2005) Relationship between CYP2D6 and SULT1A1 genotypes and serum concen- trations of tamoxifen and its metabolites during steady state treatment in breast cancer patients. In: 28th annual San Antonio breast cancer symposium, San Antonio, TX, 08–11 Dec 2005

    Google Scholar 

  • Goetz MP, Rae JM, Suman VJ et al (2005) Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 23(36):9312–9318

    Article  CAS  PubMed  Google Scholar 

  • Goetz MP, Suman VJ, Hoskin TL et al (2013) CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8. Clin Cancer Res 19(2):500–507

    Article  CAS  PubMed  Google Scholar 

  • Green H, Soderkvist P, Rosenberg P et al (2009) Pharmacogenetic studies of paclitaxel in the treatment of ovarian cancer. Basic Clin Pharmacol Toxicol 104(2):130–137

    Article  CAS  PubMed  Google Scholar 

  • Group BIGC, Mouridsen H, Giobbie-Hurder A et al (2009) Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 361(8):766–776

    Google Scholar 

  • Haiman CA, Stram DO, Pike MC et al (2003) A comprehensive haplotype analysis of CYP19 and breast cancer risk: the multiethnic cohort. Hum Mol Genet 12(20):2679–2692

    Article  CAS  PubMed  Google Scholar 

  • Haldar S, Jena N, Croce CM (1995) Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA 92(10):4507–4511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haldar S, Basu A, Croce CM (1997) Bcl2 is the guardian of microtubule integrity. Cancer Res 57(2):229–233

    CAS  PubMed  Google Scholar 

  • Hayes DF, Skaar TC, Rae JM et al (2010) Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results. Clin Pharmacol Ther 88(5):626–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heilberg IP, Hernandez E, Alonzo E et al (2005) Estrogen receptor (ER) gene polymorphism may predict the bone mineral density response to raloxifene in postmenopausal women on chronic hemodialysis. Ren Fail 27(2):155–161

    Article  CAS  PubMed  Google Scholar 

  • Henry NL, Giles JT, Ang D et al (2008) Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 111(2):365–372

    Article  CAS  PubMed  Google Scholar 

  • Henry NL, Rae JM, Li L et al (2009) Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. Breast Cancer Res Treat 117(3):571–575

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Henry NL, Nguyen A, Azzouz F et al (2010) Lack of association between oestrogen receptor polymorphisms and change in bone mineral density with tamoxifen therapy. Br J Cancer 102(2):294–300

    Article  CAS  PubMed  Google Scholar 

  • Hertz DL, McLeod HL, Irvin WJ Jr (2012a) Tamoxifen and CYP2D6: a contradiction of data. Oncologist 17(5):620–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hertz DL, Walko CM, Bridges AS et al (2012b) Pilot study of rosiglitazone as an in vivo probe of paclitaxel exposure. Br J Clin Pharmacol 74(1):197–200

    Article  CAS  PubMed  Google Scholar 

  • Hertz DL, Roy S, Motsinger-Reif AA et al (2013) CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel. Ann Oncol 24(6):1472–1478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higgins MJ, Stearns V (2011) Pharmacogenetics of endocrine therapy for breast cancer. Annu Rev Med 62:281–293

    Article  CAS  PubMed  Google Scholar 

  • Hildebrandt M, Adjei A, Weinshilboum R et al (2009) Very important pharmacogene summary: sulfotransferase 1A1. Pharmacogenet Genomics 19(6):404–406

    Article  CAS  PubMed  Google Scholar 

  • Hill-Burns EM, Singh N, Ganguly P et al (2013) A genetic basis for the variable effect of smoking/nicotine on Parkinson’s disease. Pharmacogenomics J 13(6):530–537

    Article  CAS  PubMed  Google Scholar 

  • Huizing MT, Misser VH, Pieters RC et al (1995) Taxanes: a new class of antitumor agents. Cancer Invest 13(4):381–404

    Article  CAS  PubMed  Google Scholar 

  • Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C (2007) Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 116(3):496–526

    Article  CAS  PubMed  Google Scholar 

  • Ingle JN (2013) Pharmacogenomics of endocrine therapy in breast cancer. J Hum Genet 58(6):306–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ingle JN, Schaid DJ, Goss PE et al (2010) Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. J Clin Oncol 28(31):4674–4682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwasaki M, Hamada GS, Nishimoto IN et al (2009) Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians. Cancer Sci 100(5):927–933

    Article  CAS  PubMed  Google Scholar 

  • Janz R, Sudhof TC (1999) SV2C is a synaptic vesicle protein with an unusually restricted localization: anatomy of a synaptic vesicle protein family. Neuroscience 94(4):1279–1290

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Zhou L, Yan T, Shen Z, Shao Z, Lu J (2010) Association of sulfotransferase SULT1A1 with breast cancer risk: a meta-analysis of case-control studies with subgroups of ethnic and menopausal statue. J Exp Clin Cancer Res 29:101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin Y, Desta Z, Stearns V et al (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97(1):30–39

    Article  CAS  PubMed  Google Scholar 

  • Jin Y, Hayes DF, Li L et al (2008) Estrogen receptor genotypes influence hot flash prevalence and composite score before and after tamoxifen therapy. J Clin Oncol 26(36):5849–5854

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnson MD, Zuo H, Lee KH et al (2004) Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 85(2):151–159

    Article  CAS  PubMed  Google Scholar 

  • Jordan VC (1982) Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Breast Cancer Res Treat 2(2):123–138

    Article  CAS  PubMed  Google Scholar 

  • Jordan VC (2003) Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov 2(3):205–213

    Article  CAS  PubMed  Google Scholar 

  • Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4(4):253–265

    Article  CAS  PubMed  Google Scholar 

  • Jordan VC, Collins MM, Rowsby L, Prestwich G (1977) A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol 75(2):305–316

    Article  CAS  PubMed  Google Scholar 

  • Keating GM (2014) Bevacizumab: a review of its use in advanced cancer. Drugs 74(16):1891–1925

    Article  CAS  PubMed  Google Scholar 

  • Lash TL, Cronin-Fenton D, Ahern TP et al (2011) CYP2D6 inhibition and breast cancer recurrence in a population-based study in Denmark. J Natl Cancer Inst 103(6):489–500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee KM, Abel J, Ko Y et al (2003) Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women. Br J Cancer 88(5):675–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leskela S, Jara C, Leandro-Garcia LJ et al (2011) Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity. Pharmacogenomics J 11(2):121–129

    Article  CAS  PubMed  Google Scholar 

  • Leyland-Jones B, Gray KP, Abramovitz M et al (2015) CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial. Breast Cancer Res Treat 151(2):373–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li LW, Xu L (2012) Menopausal status modifies breast cancer risk associated with ESR1 PvuII and XbaI polymorphisms in Asian women: a HuGE review and meta-analysis. Asian Pac J Cancer Prev 13(10):5105–5111

    Article  PubMed  Google Scholar 

  • Li N, Dong J, Hu Z, Shen H, Dai M (2010) Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 121(1):177–184

    Article  CAS  PubMed  Google Scholar 

  • Lim YC, Desta Z, Flockhart DA, Skaar TC (2005) Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen. Cancer Chemother Pharmacol 55(5):471–478

    Article  CAS  PubMed  Google Scholar 

  • Lin ZN, Lin YC, Zhang X et al (2012) Differential promoter activities of functional haplotypes in the 5′-flanking region of human sulfotransferase 1A1. J Biochem Mol Toxicol 26(10):422–428

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Bai YX, Zhou JH et al (2013a) 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 14(9):18973–18988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu M, Ingle JN, Fridley BL et al (2013b) TSPYL5 SNPs: association with plasma estradiol concentrations and aromatase expression. Mol Endocrinol 27(4):657–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lunardi G, Piccioli P, Bruzzi P et al (2013) 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 137(1):167–174

    Article  CAS  PubMed  Google Scholar 

  • Ma CX, Adjei AA, Salavaggione OE et al (2005) Human aromatase: gene resequencing and functional genomics. Cancer Res 65(23):11071–11082

    Article  CAS  PubMed  Google Scholar 

  • Maguire P, Margolin S, Skoglund J et al (2005) Estrogen receptor beta (ESR2) polymorphisms in familial and sporadic breast cancer. Breast Cancer Res Treat 94(2):145–152

    Article  CAS  PubMed  Google Scholar 

  • Mao JJ, Stricker C, Bruner D et al (2009) Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors. Cancer 115(16):3631–3639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mao JJ, Su HI, Feng R et al (2011) Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors. Breast Cancer Res 13(1):R8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marsh S, Somlo G, Li X et al (2007) Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 7(5):362–365

    Article  CAS  PubMed  Google Scholar 

  • Mercer KE, Apostolov EO, da Costa GG et al (2010) Expression of sulfotransferase isoform 1A1 (SULT1A1) in breast cancer cells significantly increases 4-hydroxytamoxifen-induced apoptosis. Int J Mol Epidemiol Genet 1(2):92–103

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miles DW, de Haas SL, Dirix LY et al (2013) Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Br J Cancer 108(5):1052–1060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676

    Article  CAS  PubMed  Google Scholar 

  • Miyoshi Y, Iwao K, Ikeda N, Egawa C, Noguchi S (2000) Breast cancer risk associated with polymorphism in CYP19 in Japanese women. Int J Cancer 89(4):325–328

    Article  CAS  PubMed  Google Scholar 

  • Molvarec A, Nagy B, Kovacs M et al (2007) Lipid, haemostatic and inflammatory variables in relation to the estrogen receptor alpha (ESR1) PvuII and XbaI gene polymorphisms. Clin Chim Acta 380(1–2):157–164

    Article  CAS  PubMed  Google Scholar 

  • Mortimer JE, Flatt SW, Parker BA et al (2008) Tamoxifen, hot flashes and recurrence in breast cancer. Breast Cancer Res Treat 108(3):421–426

    Article  CAS  PubMed  Google Scholar 

  • Moyer AM, Suman VJ, Weinshilboum RM et al (2011) SULT1A1, CYP2C19 and disease-free survival in early breast cancer patients receiving tamoxifen. Pharmacogenomics 12(11):1535–1543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murdter TE, Schroth W, Bacchus-Gerybadze L et al (2011) Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and II enzymes on their concentration levels in plasma. Clin Pharmacol Ther 89(5):708–717

    Article  CAS  PubMed  Google Scholar 

  • Nakamura Y, Ratain MJ, Cox NJ, McLeod HL, Kroetz DL, Flockhart DA (2012) Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial. J Natl Cancer Inst 104(16):1264; author reply 1266–1268

    Google Scholar 

  • Napoli N, Villareal DT, Mumm S et al (2005) Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. J Bone Miner Res 20(2):232–239

    Article  CAS  PubMed  Google Scholar 

  • Napoli N, Rastelli A, Ma C et al (2013) Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with aromatase inhibitor associated bone loss in women with ER + breast cancer. Bone 55(2):309–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ning B, Nowell S, Sweeney C et al (2005) Common genetic polymorphisms in the 5’-flanking region of the SULT1A1 gene: haplotypes and their association with platelet enzymatic activity. Pharmacogenet Genomics 15(7):465–473

    Article  CAS  PubMed  Google Scholar 

  • Nowell S, Sweeney C, Winters M et al (2002) Association between sulfotransferase 1A1 genotype and survival of breast cancer patients receiving tamoxifen therapy. J Natl Cancer Inst 94(21):1635–1640

    Article  CAS  PubMed  Google Scholar 

  • Nowell SA, Ahn J, Rae JM et al (2005) Association of genetic variation in tamoxifen-metabolizing enzymes with overall survival and recurrence of disease in breast cancer patients. Breast Cancer Res Treat 91(3):249–258

    Article  CAS  PubMed  Google Scholar 

  • Ntukidem NI, Nguyen AT, Stearns V et al (2008) Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen. Clin Pharmacol Ther 83(5):702–710

    Article  CAS  PubMed  Google Scholar 

  • Oger E, Lacut K, Mercier B et al (2007) Estrogen receptor alpha polymorphism and venous thromboembolism in male and female: data from the EDITH study. Thromb Res 119(4):433–439

    Article  CAS  PubMed  Google Scholar 

  • Onitilo AA, McCarty CA, Wilke RA et al (2009) Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy. Breast Cancer Res Treat 115(3):643–650

    Article  CAS  PubMed  Google Scholar 

  • Ozawa S, Tang YM, Yamazoe Y, Kato R, Lang NP, Kadlubar FF (1998) Genetic polymorphisms in human liver phenol sulfotransferases involved in the bioactivation of N-hydroxy derivatives of carcinogenic arylamines and heterocyclic amines. Chem Biol Interact 109(1–3):237–248

    Article  CAS  PubMed  Google Scholar 

  • Postma TJ, Vermorken JB, Liefting AJ, Pinedo HM, Heimans JJ (1995) Paclitaxel-induced neuropathy. Ann Oncol 6(5):489–494

    CAS  PubMed  Google Scholar 

  • Probst-Hensch NM, Ingles SA, Diep AT et al (1999) Aromatase and breast cancer susceptibility. Endocr Relat Cancer 6(2):165–173

    Article  CAS  PubMed  Google Scholar 

  • Punglia RS, Burstein HJ, Winer EP, Weeks JC (2008) Pharmacogenomic variation of CYP2D6 and the choice of optimal adjuvant endocrine therapy for postmenopausal breast cancer: a modeling analysis. J Natl Cancer Inst 100(9):642–648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rae JM, Cordero KE, Scheys JO, Lippman ME, Flockhart DA, Johnson MD (2003) Genotyping for polymorphic drug metabolizing enzymes from paraffin-embedded and immunohistochemically stained tumor samples. Pharmacogenetics 13(8):501–507

    Article  CAS  PubMed  Google Scholar 

  • Rae JM, Drury S, Hayes DF et al (2012) CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst 104(6):452–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rae JM, Regan MM, Thibert JN et al (2015) CYP2D6 genotypes obtained from tumor-derived dna are highly concordant with germline DNA genotypes obtained from patient whole blood samples. CYP2D6 genotypes obtained from tumor-derived DNA are highly concordant with germline DNA genotypes obtained from patient whole blood samples. JNCI [Epub ahead of print]

    Google Scholar 

  • Raftogianis RB, Wood TC, Otterness DM, Van Loon JA, Weinshilboum RM (1997) Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochem Biophys Res Commun 239(1):298–304

    Article  CAS  PubMed  Google Scholar 

  • Rahman A, Korzekwa KR, Grogan J, Gonzalez FJ, Harris JW (1994) Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 54(21):5543–5546

    CAS  PubMed  Google Scholar 

  • Ramsey TL, Liu Q, Massey BW, Brennan MD (2013) Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE study. Schizophr Res 149(1–3):21–25

    Article  PubMed  Google Scholar 

  • Rapuri PB, Gallagher JC, Knezetic JA, Haynatzka V (2006) Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen. Maturitas 53(4):371–379

    Article  CAS  PubMed  Google Scholar 

  • Reding KW, Chen C, Lowe K et al (2012) Estrogen-related genes and their contribution to racial differences in breast cancer risk. Cancer Causes Control 23(5):671–681

    Article  PubMed  PubMed Central  Google Scholar 

  • Regan MM, Leyland-Jones B, Bouzyk M et al (2012) CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. J Natl Cancer Inst 104(6):441–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rizzo R, Spaggiari F, Indelli M, Lelli G, Baricordi OR, Rimessi P, Ferlini A (2010) Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients. Breast Cancer Res Treat 124(2):593–598

    Google Scholar 

  • Ryan J, Canonico M, Carcaillon L et al (2012) Hormone treatment, estrogen receptor polymorphisms and mortality: a prospective cohort study. PLoS ONE 7(3):e34112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakoda LC, Blackston CR, Doherty JA et al (2011) Selected estrogen receptor 1 and androgen receptor gene polymorphisms in relation to risk of breast cancer and fibrocystic breast conditions among Chinese women. Cancer Epidemiol 35(1):48–55

    Article  CAS  PubMed  Google Scholar 

  • Saladores P, Murdter T, Eccles D et al (2015) Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J 15(1):84–94

    Article  CAS  PubMed  Google Scholar 

  • Salmen T, Heikkinen AM, Mahonen A et al (2000) Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women: effect of hormone replacement therapy. J Bone Miner Res 15(2):315–321

    Article  CAS  PubMed  Google Scholar 

  • Schneider BP, Sledge GW Jr (2007) Drug insight: VEGF as a therapeutic target for breast cancer. Nat Clin Pract Oncol 4(3):181–189

    Article  CAS  PubMed  Google Scholar 

  • Schneider BP, Wang M, Radovich M et al (2008) Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 26(28):4672–4678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneider BP, Li L, Shen F et al (2014) Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. Br J Cancer 111(6):1241–1248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneider BP, Li L, Radovich M et al (2015) Genome-Wide Association Studies for Taxane-Induced Peripheral Neuropathy in ECOG-5103 and ECOG-1199. Clin Cancer Res 21(22):5082–5091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schroth W, Goetz MP, Hamann U et al (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302(13):1429–1436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serrano D, Lazzeroni M, Zambon CF et al (2011) Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian tamoxifen prevention trial. Pharmacogenomics J 11(2):100–107

    Article  CAS  PubMed  Google Scholar 

  • Sim SC, Ingelman-Sundberg M (2010) The human cytochrome P450 (CYP) allele nomenclature website: a peer-reviewed database of CYP variants and their associated effects. Hum Genomics 4(4):278–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith IE, Dowsett M, Ebbs SR et al (2005) 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 23(22):5108–5116

    Article  CAS  PubMed  Google Scholar 

  • Sowers MR, Symons JP, Jannausch ML, Chu J, Kardia SR (2006a) Sex steroid hormone polymorphisms, high-density lipoprotein cholesterol, and apolipoprotein A-1 from the study of women’s health across the nation (SWAN). Am J Med 119(9 Suppl 1):S61–S68

    Article  CAS  PubMed  Google Scholar 

  • Sowers MR, Wilson AL, Karvonen-Gutierrez CA, Kardia SR (2006b) Sex steroid hormone pathway genes and health-related measures in women of 4 races/ethnicities: the study of women’s health across the nation (SWAN). Am J Med 119(9 Suppl 1):S103–S110

    Article  CAS  PubMed  Google Scholar 

  • Stearns V, Johnson MD, Rae JM et al (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95(23):1758–1764

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Zang Z, Xu X et al (2011) The association of SULT1A1 codon 213 polymorphism and breast cancer susceptibility: meta-analysis from 16 studies involving 23,445 subjects. Breast Cancer Res Treat 125(1):215–219

    Article  PubMed  Google Scholar 

  • Tempfer CB, Hefler LA, Schneeberger C, Huber JC (2006) How valid is single nucleotide polymorphism (SNP) diagnosis for the individual risk assessment of breast cancer? Gynecol Endocrinol 22(3):155–159

    Article  CAS  PubMed  Google Scholar 

  • Tengstrom M, Mannermaa A, Kosma VM, Hirvonen A, Kataja V (2012) SULT1A1 rs9282861 polymorphism-a potential modifier of efficacy of the systemic adjuvant therapy in breast cancer? BMC Cancer 12:257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson AM, Johnson A, Quinlan P et al (2011) Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy. Breast Cancer Res Treat 125(1):279–287

    Article  CAS  PubMed  Google Scholar 

  • Viale G, Regan MM, Dell’Orto P et al (2011) Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Ann Oncol 22(10):2201–2207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Higuchi R, Modugno F et al (2007) Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women. Breast Cancer Res Treat 106(2):273–280

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Fu Y, Tang C, Lu S, Chu WM (2010) SULT1A1 R213H polymorphism and breast cancer risk: a meta-analysis based on 8,454 cases and 11,800 controls. Breast Cancer Res Treat 122(1):193–198

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Lu K, Song Y et al (2013) Indications of clinical and genetic predictors for aromatase inhibitors related musculoskeletal adverse events in Chinese Han women with breast cancer. PLoS ONE 8(7):e68798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe J, Harada N, Suemasu K, Higashi Y, Gotoh O, Kawajiri K (1997) Arginine-cysteine polymorphism at codon 264 of the human CYP19 gene does not affect aromatase activity. Pharmacogenetics 7(5):419–424

    Article  CAS  PubMed  Google Scholar 

  • Wegman P, Elingarami S, Carstensen J, Stal O, Nordenskjold B, Wingren S (2007) Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res 9(1):R7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu X, Hawse JR, Subramaniam M, Goetz MP, Ingle JN, Spelsberg TC (2009) The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res 69(5):1722–1727

    Article  CAS  PubMed  Google Scholar 

  • Yaffe K, Lindquist K, Sen S et al (2009) Estrogen receptor genotype and risk of cognitive impairment in elders: findings from the health ABC study. Neurobiol Aging 30(4):607–614

    Article  CAS  PubMed  Google Scholar 

  • Yu KD, Rao NY, Chen AX, Fan L, Yang C, Shao ZM (2011) A systematic review of the relationship between polymorphic sites in the estrogen receptor-beta (ESR2) gene and breast cancer risk. Breast Cancer Res Treat 126(1):37–45

    Article  CAS  PubMed  Google Scholar 

  • Zanger UM, Raimundo S, Eichelbaum M (2004) Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol 369(1):23–37

    Article  CAS  PubMed  Google Scholar 

  • Zarrabeitia MT, Hernandez JL, Valero C et al (2004) A common polymorphism in the 5’-untranslated region of the aromatase gene influences bone mass and fracture risk. Eur J Endocrinol 150(5):699–704

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. VM Institute of Research, Montreal, QC, Canada

    Mark Abramovitz

  2. Avera Cancer Institute, Sioux Falls, SD, USA

    Casey Williams

  3. Molecular and Experimental Medicine, Avera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD, 57105, USA

    Brian Leyland-Jones

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  1. Mark Abramovitz
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  2. Casey Williams
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  3. Brian Leyland-Jones
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Correspondence to Brian Leyland-Jones .

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  1. Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Sunil Badve

  2. Indiana University School of Medicine, Dept of Pathology & Laboratory Medicine Indiana University School of Medicine, Indianapolis, Indiana, USA

    Yesim Gökmen-Polar

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Abramovitz, M., Williams, C., Leyland-Jones, B. (2016). Pharmacogenomics of Breast Cancer. In: Badve, S., Gökmen-Polar, Y. (eds) Molecular Pathology of Breast Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-41761-5_24

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