Pharmacogenomics: Personalized medicine and its impact on breast cancer
Keywords:
pharmacogenomics, breast cancer, personalized medicine, drug resistance, molecular subtypes, targeted therapiesAbstract
Background: Personalized medicine in breast cancer aims to optimize treatment by classifying cancer subtypes and tailoring therapy based on individual patient profiles, including genetic and epigenetic factors. Pharmacogenomics plays a crucial role in this strategy by investigating how genetic variations affect drug metabolism and therapy response. Aim: This article reviews the impact of pharmacogenomics on personalized medicine for breast cancer, focusing on different molecular subtypes and their responses to targeted therapies. Methods: The study involved a comprehensive review of current literature, examining the molecular classification of breast cancer, the role of genetic and epigenetic factors, and advancements in pharmacogenomics. Key resources, including open-source databases and clinical trials, were analyzed to understand treatment resistance and efficacy. Results: Breast cancer is categorized into molecular subtypes such as hormone receptor-positive, HER2-positive, and triple-negative. Each subtype exhibits distinct responses to therapies. For instance, hormone receptor-positive cancers benefit from endocrine therapies, while HER2-positive cancers respond to targeted antibodies. Triple-negative breast cancer, characterized by its heterogeneity, shows varied responses to platinum-based compounds and PARP inhibitors. The study highlights the challenges of drug resistance and the potential of personalized therapies to overcome these issues.
Downloads
References
Wang C, Machiraju R, Huang K. Breast cancer patient stratification using a molecular regularized consensus clustering method. Methods. 2014;67(3):304–312. doi:10.1016/j.ymeth.2014.03.00524657666
Chen X, Shachter RD, Kurian AW, Rubin DL. Dynamic strategy for personalized medicine: an application to metastatic breast cancer. J Biomed Inform. 2017;68:50–57. doi:10.1016/j.jbi.2017.02.01228232241
Nerenz RD. Pharmacogenomics and personalized medicine in the treatment of human diseases. In: Coleman WB, Tsongalis GJ, editors. Molecular pathology. 2nd ed. Elsevier; New York: Chapel Hill; 2018;731–743.
Li H, Jia W. Cometabolism of microbes and host: implications for drug metabolism and drug‐induced toxicity. Clin Pharmacol Ther. 2013;94(5):574–581. doi:10.1038/clpt.2013.15723933971
Nandy A, Gangopadhyay S, Mukhopadhyay A. Individualizing breast cancer treatment—the dawn of personalized medicine. Exp Cell Res. 2014;320(1):1–11. doi:10.1016/j.yexcr.2013.09.00224051330
Alomar MJ. Factors affecting the development of adverse drug reactions. Saudi Pharm J. 2014;22(2):83–94. doi:10.1016/j.jsps.2013.02.00324648818
Dickmann LJ, Ware JA. Pharmacogenomics in the age of personalized medicine. Drug Discov Today Technol. 2016;21:11–16. doi:10.1016/j.ddtec.2016.11.00327978982
Eroles P, Bosch A, Pérez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev. 2012;38(6):698–707. doi:10.1016/j.ctrv.2011.11.00522178455
Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747. doi:10.1038/3502055710963602
Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci. 2001;98(19):10869–10874. doi:10.1073/pnas.19136709811553815
Herschkowitz JI, Simin K, Weigman VJ, et al. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol. 2007;8(5):R76. doi:10.1186/gb-2007-8-5-r8117493263
Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol. 2011;5(1):5–23. doi:10.1016/j.molonc.2010.11.00321147047
Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2011;16(Supplement 1):61–70. doi:10.1634/theoncologist.2011-S1-61
Sørlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc National Acad Sci. 2003;100(14):8418–8423. doi:10.1073/pnas.0932692100
Stefansson OA, Esteller M. Epigenetic modifications in breast cancer and their role in personalized medicine. Am J Pathol. 2013;183(4):1052–1063. doi:10.1016/j.ajpath.2013.04.03323899662
Gnant M, Harbeck N, St. Gallen TC. summary of the consensus discussion. Breast Care. 2011;6(2
Del Mastro L, De Placido S, Bruzzi P, et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2×2 factorial, randomised phase 3 trial. Lancet. 2015;385(9980):1863–1872. doi:10.1016/S0140-6736(14)62048-125740286
Creighton CJ. The molecular profile of luminal B breast cancer. Biologics. 2012;6:289.22956860
Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11(16):5678–5685. doi:10.1158/1078-0432.CCR-04-242116115903
Network CGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61. doi:10.1038/nature1141223000897
Colozza M, de Azambuja E, Cardoso F, Bernard C, Piccart MJ. Breast cancer: achievements in adjuvant systemic therapies in the pre-genomic era. Oncologist. 2006;11(2):111–125. doi:10.1634/theoncologist.11-2-11116476832
Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA. 2006;295(21):2492–2502. doi:10.1001/jama.295.21.249216757721
Rakha EA, El-Rehim DA, Paish C, et al. Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer. 2006;42(18):3149–3156. doi:10.1016/j.ejca.2006.08.01517055256
Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10(16):5367–5374. doi:10.1158/1078-0432.CCR-04-022015328174
Weigelt B, Mackay A, A‘Hern R, et al. Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol. 2010;11(4):339–349.
Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68. doi:10.1186/bcr272220813035
Cadoo KA, Traina TA, King TA. Advances in molecular and clinical subtyping of breast cancer and their implications for therapy. Surg Oncol Clin. 2013;22(4):823–840. doi:10.1016/j.soc.2013.06.006
Fang L, Barekati Z, Zhang B, Liu Z, Zhong X. Targeted therapy in breast cancer: what’s new. Swiss Med Wkly. 2011;141:w13231.21706452
Ng CK, Martelotto LG, Gauthier A, et al. Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification. Genome Biol. 2015;16(1):107. doi:10.1186/s13059-015-0667-425994018
Zardavas D, Irrthum A, Swanton C, Piccart M. Clinical management of breast cancer heterogeneity. Nat Rev Clin Oncol. 2015;12(7):381. doi:10.1038/nrclinonc.2015.7325895611
Tsai H-F, Trubelja A, Shen AQ, Bao G. Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment. J R Soc Interface. 2017;14(131):20170137. doi:10.1098/rsif.2017.013728637915
Ahn J, Sei Y, Jeon N, Kim Y. Tumor microenvironment on a chip: the progress and future perspective. Bioengineering. 2017;4(3):64. doi:10.3390/bioengineering4020044
Peters ML, Garber JE, Tung N. Managing hereditary breast cancer risk in women with and without ovarian cancer. Gynecol Oncol. 2017;146(1):205–214. doi:10.1016/j.ygyno.2017.04.01328454658
Kristiansen S, Nielsen D, Sölétormos G. Detection and monitoring of hypermethylated RASSF1A in serum from patients with metastatic breast cancer. Clin Epigen. 2016;8(1):35. doi:10.1186/s13148-016-0199-0
Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30.10592173
Sangodkar J, Farrington CC, McClinch K, Galsky MD, Kastrinsky DB, Narla G. All roads lead to PP 2A: exploiting the therapeutic potential of this phosphatase. FEBS J. 2016;283(6):1004–1024. doi:10.1111/febs.1357326507691
Lau QC, Raja E, Salto-Tellez M, et al. RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res. 2006;66(13):6512–6520. doi:10.1158/0008-5472.CAN-06-036916818622
Pietras RJ, Márquez-Garbán DC. Membrane-associated estrogen receptor signaling pathways in human cancers. Clin Cancer Res. 2007;13(16):4672–4676. doi:10.1158/1078-0432.CCR-07-137317699844
Russell CA. Personalized medicine for breast cancer: it is a new day! Am J Surg. 2014;207(3):321–325. doi:10.1016/j.amjsurg.2013.10.01624581758
Barone I, Brusco L, Fuqua SA. Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin Cancer Res. 2010;15;16(10):1078–1432. CCR-09-1753.
De Abreu FB, Wells WA, Tsongalis GJ. The emerging role of the molecular diagnostics laboratory in breast cancer personalized medicine. Am J Pathol. 2013;183(4):1075–1083. doi:10.1016/j.ajpath.2013.07.00223920325
Yanagawa T, Kagara N, Miyake T, et al. Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing. Breast Cancer Res Treat. 2017;163(2):231–240. doi:10.1007/s10549-017-4190-z28283903
Mayer IA. Advanced hormone-sensitive breast cancer: overcoming resistance. J Natl Compr Canc Netw. 2015;13(5S):655–657.25995422
Downey C, Simpkins S, White J, et al. The prognostic significance of tumour–stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer. 2014;110(7):1744. doi:10.1038/bjc.2014.6924548861
Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, et al. Clinical significance of monitoring ESR1 mutations in circulating cell-free DNA in estrogen receptor positive breast cancer patients. Oncotarget. 2016;7(22):32504. doi:10.18632/oncotarget.883927102299
Tabarestani S, Motallebi M, Akbari ME. Are estrogen receptor genomic aberrations predictive of hormone therapy response in breast cancer? Iran J Cancer Prev. 2016;9:4. doi:10.17795/ijcp
Segal CV, Dowsett M. Estrogen receptor mutations in breast cancer—new focus on an old target. Clin Cancer Res. 2014;20(7):1724–1726. doi:10.1158/1078-0432.CCR-14-006724583794
Fribbens C, O‘Leary B, Kilburn L, et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34:2961–2968.
Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425–439. doi:10.1016/S1470-2045(15)00613-026947331
Lauring J, Wolff AC. Evolving role of the estrogen receptor as a predictive biomarker: ESR1 mutational status and endocrine resistance in breast cancer. J Clin Oncol. 2016;34(25):2950–2952. doi:10.1200/JCO.2016.68.472027382095
Gelsomino L, Gu G, Rechoum Y, et al. ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling. Breast Cancer Res Treat. 2016;157(2):253–265. doi:10.1007/
Fuqua SA, Gu G, Rechoum Y. Estrogen receptor (ER) α mutations in breast cancer: hidden in plain sight. Breast Cancer Res Treat. 2014;144(1):11–19. doi:10.1007/s10549-014-2847-424487689
Fu X, Creighton CJ, Biswal NC, et al. Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase. Breast Cancer Res. 2014;16(5):430. doi:10.1186/s13058-014-0492-925212826
Rimawi MF, Wiechmann LS, Wang Y-C, et al. Reduced dose and intermittent treatment with lapatinib and trastuzumab for potent blockade of the HER pathway in HER2/neu-overexpressing breast tumor xenografts. Clin Cancer Res. 2011;17(6):1351–1361. doi:10.1158/1078-0432.CCR-10-190521138857
Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, et al. Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients. Oncotarget. 2017;8(32):52142. doi:10.18632/oncotarget.1847928881720
Van Loo P, Wedge D, Nik-Zainal S, Stratton M, Futreal P, Campbell P. 5 proffered paper: the life history of 21 breast cancers. Eur J Cancer. 2012;48:S2. doi:10.1016/S0959-8049(12)70709-8
Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, et al. Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens. Transl Res. 2015;166(6):540–53. e2. doi:10.1016/j.trsl.2015.09.00326434753
Perez EA. Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treatment order. Drug Resist Update. 2016;24:13–22. doi:10.1016/j.drup.2015.11.001
Zanardi E, Bregni G, De Braud F, Di Cosimo S, editors. Better together: targeted combination therapies in breast cancer. Semin Oncol. 2015. Elsevier. doi:10.1053/j.seminoncol.2015.09.029
Garber JE, Halabi S, Tolaney SM, et al. Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer. J Natl Cancer Inst. 2010;102(13):942–949. doi:10.1093/jnci/djq21120554945
Onitilo AA, McCarty CA, Wilke RA, et al. Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy. Breast Cancer Res Treat. 2009;115(3):643–650. doi:10.1007/s10549-008-0264-219082882
Conway K, Parrish E, Edmiston SN, et al. The estrogen receptor-α A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: results from a population-based study. Breast Cancer Res. 2005;7(6):R871. doi:10.1186/bcr94916280033
Roodi N, Bailey LR, Kao W-Y, et al. Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. Jnci. 1995;87(6):446–451. doi:10.1093/jnci/87.6.4467861463
Weinreb I, Piscuoglio S, Martelotto LG, et al. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat Genet. 2014;46(11):1166. doi:10.1038/ng.289525240283
Ross JS, Gay LM, Wang K, et al. Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: an emerging opportunity for anti‐HER2 targeted therapies. Cancer. 2016;122(17):2654–2662. doi:10.1002/cncr.3010227284958
Carter P, Presta L, Gorman CM, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc National Acad Sci. 1992;89(10):4285–4289. doi:10.1073/pnas.89.10.4285
Gajria D, Chandarlapaty S. HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies. Expert Rev Anticancer Ther. 2011;11(2):263–275. doi:10.1586/era.10.22621342044
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–792. doi:10.1056/NEJM20010315344110111248153
Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20(3):719–726. doi:10.1200/JCO.2002.20.3.71911821453
Jahanzeb M. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008;8(4):324–333. doi:10.3816/CBC.2008.n.03718757259
Nahta R, Esteva F. Trastuzumab: triumphs and tribulations. Oncogene. 2007;26(25):3637. doi:10.1038/sj.onc.121037917530017
Bedard PL, de Azambuja E, Cardoso F. Beyond trastuzumab: overcoming resistance to targeted HER-2 therapy in breast cancer. Curr Cancer Drug Targets. 2009;9(2):148–162.19275756
Rimawi MF, Schiff R, Osborne CK. Targeting HER2 for the treatment of breast cancer. Annu Rev Med. 2015;66:111–128.
Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2012;9(1):16. doi:10.1038/nrclinonc.2012.154
Yamaguchi H, Chang S, Hsu J, Hung M. Signaling cross-talk in the resistance to HER family receptor targeted therapy. Oncogene. 2014;33(9):1073. doi:10.1038/onc.2013.7423542173
Arribas J, Baselga J, Pedersen K, Parra-Palau JL. p95HER2 and breast cancer. Cancer Res. 2011;71(5):1515–1519. doi:10.1158/0008-5472.CAN-10-379521343397
Castiglioni F, Tagliabue E, Campiglio M, Pupa S, Balsari A, Menard S. Role of exon-16-deleted HER2 in breast carcinomas. Endocr Relat Cancer. 2006;13(1):221–232. doi:10.1677/erc.1.0104716601290
Mitra D, Brumlik MJ, Okamgba SU, et al. An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance. Mol Cancer Ther. 2009;8(8):2152–2162. MCT-09-0295.
Funes M, Miller JK, Lai C, Carraway KL, Sweeney C. The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3. J Biol Chem. 2006;281(28):19310–19319. doi:10.1074/jbc.M60322520016690615
Price‐Schiavi SA, Jepson S, Li P, et al. Rat Muc4 (sialomucin complex) reduces binding of anti‐ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance. Int J Cancer. 2002;99(6):783–791. doi:10.1002/ijc.1041012115478
de Melo Gagliato D, Jardim DLF, Marchesi MSP, Hortobagyi GN. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget. 2016;7(39):64431.26824988
Ferrari A, Vincent-Salomon A, Pivot X, et al. A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers. Nat Commun. 2016;7:12222. doi:10.1038/ncomms1222227406316
Kovtun YV, Goldmacher VS. Cell killing by antibody–drug conjugates. Cancer Lett. 2007;255(2):232–240. doi:10.1016/j.canlet.2007.04.01017553616
Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res. 2014;16(2):209. doi:10.1186/s13058-014-0492-924887180
Van Herpen C, Banerji U, Mommers E, et al. 333 Phase I dose-escalation trial with the DNA-alkylating anti-HER2 antibody-drug conjugate SYD985. Eur J Cancer. 2015;51:S65. doi:10.1016/S0959-8049(16)30197-6
Medina PJ, Goodin S. Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008;30(8):1426–1447. doi:10.1016/j.clinthera.2008.08.00818803986
Tevaarwerk AJ, Kolesar JM. Lapatinib: A small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer. Clin Ther. 2009;31:2332–2348. doi:10.1016/j.clinthera.2009.11.02920110044
Konecny GE, Pegram MD, Venkatesan N, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 2006;66(3):1630–1639. doi:10.1158/0008-5472.CAN-05-118216452222
Vicario R, Peg V, Morancho B, et al. Patterns of HER2 gene amplification and response to anti-HER2 therapies. PLoS One. 2015;10(6):e0129876. doi:10.1371/journal.pone.012987626075403
Hafizi S, Dahlbäck B. Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev. 2006;17(4):295–304. doi:10.1016/j.cytogfr.2006.04.00416737840
Franklin MC, Carey KD, Vajdos FF, Leahy DJ, De Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004;5(4):317–328.15093539
Agus DB, Gordon MS, Taylor C, et al. Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J clin oncol. 2005;23(11):2534–2543. doi:10.1200/JCO.2005.03.18415699478
Leung W-Y, Roxanis I, Sheldon H, et al. Combining lapatinib and pertuzumab to overcome lapatinib resistance due to NRG1-mediated signalling in HER2-amplified breast cancer. Oncotarget. 2015;6(8):5678. doi:10.18632/oncotarget.329625691057
Hyman D, Piha-Paul S, Rodón J, et al. editors. Neratinib for ERBB2 mutant, HER2 non-amplified, metastatic breast cancer: preliminary analysis from a multicenter, open-label, multi-histology phase II basket trial. Cancer Res. 2016. AMER ASSOC CANCER RESEARCH 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA …. doi:10.1158/1538-7445.SABCS15-PD5-05
Subramaniam D, He A R, Hwang J, et al. Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer. Curr Cancer Drug Targets. 2014;14(9):775–793. doi:10.2174/1568009614666141111104643
Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(3):367–377. doi:10.1016/S1470-2045(15)00551-326874901
Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27(34):4702. doi:10.1038/onc.2008.10918408761
Hurvitz SA, Shatsky R, Harbeck N. Afatinib in the treatment of breast cancer. Expert Opin Investig Drugs. 2014;23(7):1039–1047. doi:10.1517/13543784.2014.924505
Gunzer K, Joly F, Ferrero J-M, et al. A phase II study of afatinib, an irreversible ErbB family blocker, added to letrozole in patients with estrogen receptor-positive hormone-refractory metastatic breast cancer progressing on letrozole. Springerplus. 2016;5(1):45. doi:10.1186/s40064-015-1601-726835225
Judes G, Rifaï K, Daures M, et al. High-throughput «Omics» technologies: new tools for the study of triple-negative breast cancer. Cancer Lett. 2016;382(1):77–85. doi:10.1016/j.canlet.2016.03.00126965997
Telli ML, Hellyer J, Audeh W, et al. Homologous recombination deficiency (HRD) status predicts response to standard neoadjuvant chemotherapy in patients with triple-negative or BRCA1/2 mutation-associated breast cancer. Breast Cancer Res Treat. 2018;168(3):625–630. doi:10.1007/s10549-017-4624-729275435
Shah SP, Roth A, Goya R, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012;486(7403):395. doi:10.1038/nature1093322495314
Foedermayr M, Sebesta M, Rudas M, et al. BRCA-1 methylation and TP53 mutation in triple-negative breast cancer patients without pathological complete response to taxane-based neoadjuvant chemotherapy. Cancer Chemother Pharmacol. 2014;73(4):771–778. doi:10.1007/s00280-014-2404-124526178
Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfjord JE. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006;8(4):R38. doi:10.1186/bcr152216846527
Gudmundsdottir K, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene. 2006;25(43):5864. doi:10.1038/sj.onc.120987416998501
O‘Shaughnessy J, Schwartzberg L, Danso M, et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol. 2011;29(15_suppl):1007. doi:10.1200/jco.2011.29.15_suppl.100721205758
Patel AG, De Lorenzo SB, Flatten KS, Poirier GG, Kaufmann SH. Failure of iniparib to inhibit poly (ADP-Ribose) polymerase in vitro. Clin Cancer Res. 2012;15;18(6):1655–1662.
Reles A, Wen WH, Schmider A, et al. Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer. Clin Cancer Res. 2001;7(10):2984–2997.11595686
Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Breast Cancer Chemosensitivity. 2007;608:1–22.
Gewirtz D. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57(7):727–741. doi:10.1016/S0006-2952(98)00307-410075079
Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185–229. doi:10.1124/pr.56.2.615169927
Senchenkov A, Litvak DA, Cabot MC. Targeting ceramide metabolism—a strategy for overcoming drug resistance. J Natl Cancer Inst. 2001;93(5):347–357.11238696
Chen G, J-P J, Fleming WH, Durán GE, Sikic BI. Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single-step doxorubicin selection. Cancer Res. 1994;54(18):4980–4987.7915196
Larsen AK, Skladanowski A. Cellular resistance to topoisomerase-targeted drugs: from drug uptake to cell death. Biochim Biophys Acta. 1998;1400(1–3):257–274. doi:10.1016/S0167-4781(98)00140-79748618
Withoff S, De SJ, De EV, Mulder N. Human DNA topoisomerase II: biochemistry and role in chemotherapy resistance. Anticancer Res. 1996;16(4A):1867–1880.8712715
Finlay GJ, Baguley BC, Snow K, Judd W. Multiple patterns of resistance of human leukemia cell sublines to amsacrine analogues. Jnci. 1990;82(8):662–667. doi:10.1093/jnci/82.8.6622157028
Seidman AD, Reichman BS, Crown J, et al. Paclitaxel as second and subsequent therapy for metastatic breast cancer: activity independent of prior anthracycline response. J Clin Oncol. 1995;13(5):1152–1159. doi:10.1200/JCO.1995.13.5.11527537798
Wilson WH, Berg SL, Bryant G, et al. Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96 hr infusion. J Clin Oncol. 1994;12(8):1621–1629. doi:10.1200/JCO.1994.12.8.16217913721
Anderson H, Hopwood P, Prendiville J, Radford JA, Thatcher N, Ashcroft L. A randomised study of bolus vs continuous pump infusion of ifosfamide and doxorubicin with oral etoposide for small cell lung cancer. Br J Cancer. 1993;67(6):1385. doi:10.1038/bjc.1993.2568390287
Bristol-Myers Squibb. Taxol® (paclitaxel) [Prescribing information]. New York: Bristol-Myers Squibb; 2011.
Greenberger L, Williams SS, Horwitz SB. Biosynthesis of heterogeneous forms of multidrug resistance-associated glycoproteins. J Biol Chem. 1987;262(28):13685–13689.2888763
Tolcher A, Cowan K, Solomon D, et al. Phase I crossover study of paclitaxel with r-verapamil in patients with metastatic breast cancer. J clin oncol. 1996;14(4):1173–1184. doi:10.1200/JCO.1996.14.4.11738648372
Twelves C, Jove M, Gombos A, Awada A. Cytotoxic chemotherapy: still the mainstay of clinical practice for all subtypes metastatic breast cancer. Crit Rev Oncol Hematol. 2016;100:74–87. doi:10.1016/j.critrevonc.2016.01.02126857987
Jameson GS, Hamm JT, Weiss GJ, et al. A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors. Clin Cancer Res. 2013;19(1):268–278. doi:10.1158/1078-0432.CCR-12-120123136196
Hoch U, Staschen C-M, Johnson RK, Eldon MA. Nonclinical pharmacokinetics and activity of etirinotecan pegol (NKTR-102), a long-acting topoisomerase 1 inhibitor, in multiple cancer models. Cancer Chemother Pharmacol. 2014;74(6):1125–1137. doi:10.1007/s00280-014-2577-725228368
Huennekens F. The methotrexate story: a paradigm for development of cancer chemotherapeutic agents. Adv Enzyme Regul. 1994;34:397–419.7942284
Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330. doi:10.1038/nrc107412724731
Grant SC, Kris MG, Young CW, Sirotnak FM. Edatrexate, an antifolate with antitumor activity: a review. Cancer Invest. 1993;11(1):36–45.8422595
Sirotnak F, Moccio D, Kelleher L, Goutas L. Relative frequency and kinetic properties of transport-defective phenotypes among methotrexate-resistant L1210 clonal cell lines derived in vivo. Cancer Research. 1981;41(11 Pt 1):4447–4452.
Kool M, Van Der Linden M, de Haas M, et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc National Acad Sci. 1999;96(12):6914–6919. doi:10.1073/pnas.96.12.6914
Hooijberg J, Broxterman H, Scheffer G, et al. Potent interaction of flavopiridol with MRP1. Br J Cancer. 1999;81(2):269. doi:10.1038/sj.bjc.669068710496352
Cowan KH, Jolivet J. A methotrexate-resistant human breast cancer cell line with multiple defects, including diminished formation of methotrexate polyglutamates. J Biol Chem. 1984;259(17):10793–10800.6206061
Volk EL, Rohde K, Rhee M, et al. Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux. Cancer Res. 2000;60(13):3514–3521.10910063
Ohmori T, Podack E, Nishio K, et al. Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2. Biochem Biophys Res Commun. 1993;192(1):30–36.8476431
Priest DG, Ledford BE, Doig MT. Increased thymidylate synthetase in 5-fluorodeoxyuridine resistant cultured hepatoma cells. Biochem Pharmacol. 1980;29(11):1549–1553.6446915
Spears CP. Clinical resistance to antimetabolites. Hematol Oncol Clin North Am. 1995;9(2):397–414.7642470
Klatt O, Stehlin JS, McBride C, Griffin A. The effect of nitrogen mustard treatment on the deoxyribonucleic acid of sensitive and resistant Ehrlich tumor cells. Cancer Res. 1969;29(2):286–290.5765411
Ichiro N, Kimitoshi K, Junko K, et al. Analysis of structural features of dihydropyridine analogs needed to reverse multidrug resistance and to inhibit photoaffinity labeling of P-glycoprotein. Biochem Pharmacol. 1989;38(3):519–527.2563655
Zamble DB, Lippard SJ. Cisplatin and DNA repair in cancer chemotherapy. Trends Biochem Sci. 1995;20(10):435–439.8533159
Perez R. Cellular and molecular determinants of cisplatin resistance. Eur J Cancer. 1998;34(10):1535–1542.9893624
Moudi M, Go R, Yien CYS, Nazre M. Vinca alkaloids. Int J Prev Med. 2013;4(11):1231.24404355
Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36–48. doi:10.1016/j.addr.2012.09.03723036225
Coyle C, Cafferty F, Vale C, Langley R. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Ann Oncol. 2016;27(12):2184–2195. doi:10.1093/annonc/mdw41027681864
Zhang J, Li G, Chen Y, et al. Metformin Inhibits tumorigenesis and tumor growth of breast cancer cells by upregulating miR-200c but downregulating AKT2 expression. J Cancer. 2017;8(10):1849. doi:10.7150/jca.1985828819383
Al-Zaidan L, Ruz E, Abu R, Malki AM. Screening novel molecular targets of metformin in breast cancer by proteomic approach. Front Public Health. 2017;5:277. doi:10.3389/fpubh.2017.0008129085821
Obaidi J, Musallam E, Al-Ghzawi HM, Azzeghaiby SN, Alzoghaibi IN. Vitamin D and its relationship with breast cancer: an evidence based practice paper. Glob J Health Sci. 2015;7(1):261.
Gall TL, Kristjansson E, Charbonneau C, Florack P. A longitudinal study on the role of spirituality in response to the diagnosis and treatment of breast cancer. J Behav Med. 2009;32(2):174–186. doi:10.1007/s10865-008-9182-318982441
Chida Y, Hamer M, Wardle J, Steptoe A. Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat Rev Clin Onco. 2008;5(8):466. doi:10.1038/ncponc1134
MacArthur AC, Le ND, Abanto ZU, Gallagher RP. Occupational female breast and reproductive cancer mortality in British Columbia, Canada, 1950–94. Occup Med (Chic Ill). 2007;57(4):246–253. doi:10.1093/occmed/kqm002
Akbari ME, Kashani FL, Ahangari G, et al. The effects of spiritual intervention and changes in dopamine receptor gene expression in breast cancer patients. Breast Cancer. 2016;23(6):893–900. doi:10.1007/s12282-015-0658-z26597879
Hejazi SH, Ahangari G, Pornour M, et al. Evaluation of gene expression changes of serotonin receptors, 5-HT3AR and 5-HT2AR as main stress factors in breast cancer patients. Asian Pac J Cancer Prev. 2013;15(11):4455–4458. doi:10.7314/APJCP.2014.15.11.4455
Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G. The microbiota of breast tissue and its association with tumours. Appl Environ Microbiol. 2016;AEM: 01235–16.
Toga AW, Foster I, Kesselman C, et al. Big biomedical data as the key resource for discovery science. JAMIA. 2015;22(6):1126–1131. doi:10.1093/jamia/ocv07726198305
Kanehisa M, Goto S. KEGG: Breast cancer - Reference pathway; 2018 Available at: https://www.genome.jp/kegg-bin/show_pathway?map05224. Accessed May 15, 2019
Jeibouei, S., Akbari, M. E., Kalbasi, A., Aref, A. R., Ajoudanian, M., Rezvani, A., & Zali, H. (2019). Personalized medicine in breast cancer: pharmacogenomics approaches. Pharmacogenomics and personalized medicine, 59-73.
Published
How to Cite
Issue
Section
Copyright (c) 2019 International journal of health sciences

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Articles published in the International Journal of Health Sciences (IJHS) are available under Creative Commons Attribution Non-Commercial No Derivatives Licence (CC BY-NC-ND 4.0). Authors retain copyright in their work and grant IJHS right of first publication under CC BY-NC-ND 4.0. Users have the right to read, download, copy, distribute, print, search, or link to the full texts of articles in this journal, and to use them for any other lawful purpose.
Articles published in IJHS can be copied, communicated and shared in their published form for non-commercial purposes provided full attribution is given to the author and the journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
This copyright notice applies to articles published in IJHS volumes 4 onwards. Please read about the copyright notices for previous volumes under Journal History.