Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 5/2013

01-10-2013 | Review

Clinical application of high-throughput genomic technologies for treatment selection in breast cancer

Authors: Aaron R Hansen, Philippe L Bedard

Published in: Breast Cancer Research | Issue 5/2013

Login to get access

Abstract

Large-scale collaborative initiatives using next-generation DNA sequencing and other high-throughput technologies have begun to characterize the genomic landscape of breast cancer. These landmark studies have identified infrequent driver mutations that are potential targets for therapeutic intervention with approved or investigational drug treatments, among other important discoveries. Recently, many institutions have launched molecular screening programs that apply high-throughput genomic technologies to patients with advanced solid malignancies, including breast cancer, to inform clinical decision-making. This article provides an overview of the recent molecular insights in breast cancer, including potentially actionable somatic alterations, the technological platforms currently available in a clinical diagnostics setting to detect these alterations, and ongoing institutional or regional molecular screening programs in advanced breast cancer.
Literature
1.
Cancer Genome Atlas Network: Comprehensive molecular portraits of human breast tumours. Nature. 2012, 490: 61-70. 10.1038/nature11412.CrossRef
2.
Sotiriou C, Pusztai L: Gene-expression signatures in breast cancer. N Engl J Med. 2009, 360: 790-800. 10.1056/NEJMra0801289.CrossRefPubMed
3.
Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A, Emery C, Greulich H, Shah K, Sasaki H, Gazdar A, Minna J, Armstrong SA, et al: High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007, 39: 347-351. 10.1038/ng1975.CrossRefPubMed
4.
5.
Meyerson M, Gabriel S, Getz G: Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010, 11: 685-696. 10.1038/nrg2841.CrossRefPubMed
6.
Biesecker LG, Burke W, Kohane I, Plon SE, Zimmern R: Next-generation sequencing in the clinic: are we ready?. Nat Rev Genet. 2012, 13: 818-824. 10.1038/nrg3357.CrossRefPubMedPubMedCentral
7.
8.
Eifert C, Powers RS: From cancer genomes to oncogenic drivers, tumour dependencies and therapeutic targets. Nat Rev Cancer. 2012, 12: 572-578. 10.1038/nrc3299.CrossRefPubMed
9.
Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, et al: Patterns of somatic mutation in human cancer genomes. Nature. 2007, 446: 153-158. 10.1038/nature05610.CrossRefPubMedPubMedCentral
10.
Kola I, Landis J: Can the pharmaceutical industry reduce attrition rates?. Nat Rev Drug Discov. 2004, 3: 711-716. 10.1038/nrd1470.CrossRefPubMed
11.
12.
Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Falchook GS, Fu S, Piha-Paul SA, Naing A, Janku F, Luthra R: Personalized medicine in a phase I clinical trials program: The MD Anderson Cancer Center Initiative. Clin Cancer Res. 2012, 18: 6373-6383. 10.1158/1078-0432.CCR-12-1627.CrossRefPubMedPubMedCentral
13.
Juric D, Rodon J, Gonzalez-Angulo AM, Burris HA, Bendell J, Berlin JD, Middleton MR, Bootle D, Boehm M, Schmitt A, Rouyrre N, Quadt C, Baselga J: BYL719, a next generation PI3K alpha specific inhibitor: preliminary safety, PK, and efficacy results from the first-in-human study. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research. March 31-April 4, 2012. 2012, Chicago, IL: American Association for Cancer Research, Abstract CT-01
14.
Dienstmann R, Andre F, Soria J, Tabernero J, De Braud FGM, Cereda R, Bahleda R, Hollebecque A, Delmonte A, Camboni MG: Significant antitumor activity of E-3810, a novel FGFR and VEGFR inhibitor, in patients with FGFR1 amplified breast cancer. Ann Oncol. 2012, 23: ix116-ix143. 10.1093/annonc/mds393.
15.
Andre F, Delaloge S, Soria JC: Biology-driven phase II trials: what is the optimal model for molecular selection?. J Clin Oncol. 2011, 29: 1236-1238. 10.1200/JCO.2010.31.6877.CrossRefPubMed
16.
Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y: The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012, 486: 346-352.PubMedPubMedCentral
17.
Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR: The landscape of cancer genes and mutational processes in breast cancer. Nature. 2012, 486: 400-404.PubMedPubMedCentral
18.
Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, et al: The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012, 486: 395-399.PubMed
19.
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC: Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012, 486: 353-360.PubMedPubMedCentral
20.
Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L: Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012, 486: 405-409. 10.1038/nature11154.CrossRefPubMedPubMedCentral
21.
Kalinsky K, Jacks LM, Heguy A, Patil S, Drobnjak M, Bhanot UK, Hedvat CV, Traina TA, Solit D, Gerald W, Moynahan ME: PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res. 2009, 15: 5049-5059. 10.1158/1078-0432.CCR-09-0632.CrossRefPubMed
22.
Parker JS, Mullins M, Cheang MCU, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z: Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009, 27: 1160-1167. 10.1200/JCO.2008.18.1370.CrossRefPubMedPubMedCentral
23.
Baselga J, Campone M, Piccart M, Burris HA, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN: Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012, 366: 520-529. 10.1056/NEJMoa1109653.CrossRefPubMed
24.
Kaufman P, Ferrero J, Bourgeois H, Kennecke H, De Boer R, Jacot W, McGreivy J, Suzuki S, Loh E, Robertson J: Abstract S1-4: a randomized, double-blind, placebo-controlled, phase 2 study of AMG 479 with exemestane (E) or fulvestrant (F) in postmenopausal women with hormone-receptor positive (HR+) metastatic (M) or locally advanced (LA) breast cancer (BC). Cancer Res. 2011, 70: S1-S4.
25.
Wellbrock C, Karasarides M, Marais R: The RAF proteins take centre stage. Nat Rev Mol Cell Biol. 2004, 5: 875-885. 10.1038/nrm1498.CrossRefPubMed
26.
Engelman JA: Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009, 9: 550-562. 10.1038/nrc2664.CrossRefPubMed
27.
Wang F, Wang L, Briggs C, Sicinska E, Gaston SM, Mamon H, Kulke MH, Zamponi R, Loda M, Maher E, Ogino S, Fuchs CS, Li J, Hader C, Makrigiorgos GM: DNA degradation test predicts success in whole-genome amplification from diverse clinical samples. J Mol Diagn. 2007, 9: 441-451. 10.2353/jmoldx.2007.070004.CrossRefPubMedPubMedCentral
28.
Adams MD, Veigl ML, Wang Z, Molyneux N, Sun S, Guda K, Yu X, Markowitz SD, Willis J: Global mutational profiling of formalin-fixed human colon cancers from a pathology archive. Mod Pathol. 2012, 25: 1599-1608. 10.1038/modpathol.2012.121.CrossRefPubMedPubMedCentral
29.
Hadd AG, Houghton J, Choudhary A, Sah S, Chen L, Marko AC, Sanford T, Buddavarapu K, Krosting J, Garmire L, Wylie D, Shinde R, Beaudenon S, Alexander EK, Mambo E, Adai AT, Latham GJ: Targeted, high-depth, next-generation sequencing of cancer genes in formalin-fixed, paraffin-embedded and fine-needle aspiration tumor specimens. J Mol Diagn. 2013, 15: 234-247. 10.1016/j.jmoldx.2012.11.006.CrossRefPubMed
30.
Wagle N, Berger MF, Davis MJ, Blumenstiel B, Defelice M, Pochanard P, Ducar M, Van Hummelen P, Macconaill LE, Hahn WC, Meyerson M, Gabriel SB, Garraway LA: High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov. 2012, 2: 82-93. 10.1158/2159-8290.CD-11-0184.CrossRefPubMed
31.
Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A, Tannock IF, Clemons M: Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012, 30: 587-592. 10.1200/JCO.2010.33.5232.CrossRefPubMed
32.
van Diest PJ, Hoefnagel LDC, van der Wall E: Testing for discordance at metastatic relapse of breast cancer matters. J Clin Oncol. 2012, 30: 3031-CrossRefPubMed
33.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012, 366: 883-892. 10.1056/NEJMoa1113205.CrossRefPubMedPubMedCentral
34.
Ross JS, Cronin M: Whole cancer genome sequencing by next-generation methods. Am J Clin Pathol. 2011, 136: 527-539. 10.1309/AJCPR1SVT1VHUGXW.CrossRefPubMed
35.
Gargis AS, Kalman L, Berry MW, Bick DP, Dimmock DP, Hambuch T, Lu F, Lyon E, Voelkerding KV, Zehnbauer BA: Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol. 2012, 30: 1033-1036. 10.1038/nbt.2403.CrossRefPubMed
36.
MacConaill LE, Campbell CD, Kehoe SM, Bass AJ, Hatton C, Niu L, Davis M, Yao K, Hanna M, Mondal C, Luongo L, Emery CM, Baker AC, Philips J, Goff DJ, Fiorentino M, Rubin MA, Polyak K, Chan J, Wang Y, Fletcher JA, Santagata S, Corso G, Roviello F, Shivdasani R, Kieran MW, Ligon KL, Stiles CD, Hahn WC, Meyerson ML, et al: Profiling critical cancer gene mutations in clinical tumor samples. PLoS One. 2009, 4: e7887-10.1371/journal.pone.0007887.CrossRefPubMedPubMedCentral
37.
Dias-Santagata D, Akhavanfard S, David SS, Vernovsky K, Kuhlmann G, Boisvert SL, Stubbs H, McDermott U, Settleman J, Kwak EL, Clark JW, Isakoff SJ, Sequist LV, Engelman JA, Lynch TJ, Haber DA, Louis DN, Ellisen LW, Borger DR, Iafrate AJ: Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine. EMBO Mol Med. 2010, 2: 146-158. 10.1002/emmm.201000070.CrossRefPubMedPubMedCentral
38.
Von Hoff DD, Stephenson JJ, Rosen P, Loesch DM, Borad MJ, Anthony S, Jameson G, Brown S, Cantafio N, Richards DA, Fitch TR, Wasserman E, Fernandez C, Green S, Sutherland W, Bittner M, Alarcon A, Mallery D, Penny R: Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol. 2010, 28: 4877-4883. 10.1200/JCO.2009.26.5983.CrossRefPubMed
39.
Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Fu S, Piha-Paul SA, Naing A, Falchook GS, Janku F, Luthra R, Wen S, Kurzrock R: Personalized medicine in a phase I clinical trials program: The M. D. Anderson Cancer Center Initiative. J Clin Oncol. 2011, 29: abstr CRA2500-
40.
Sequist LV, Heist RS, Shaw AT, Fidias P, Rosovsky R, Temel JS, Lennes IT, Digumarthy S, Waltman BA, Bast E, Tammireddy S, Morrissey L, Muzikansky A, Goldberg SB, Gainor J, Channick CL, Wain JC, Gaissert H, Donahue DM, Muniappan A, Wright C, Willers H, Mathisen DJ, Choi NC, Baselga J, Lynch TJ, Ellisen LW, Mino-Kenudson M, Lanuti M, Borger DR, et al: Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol. 2011, 22: 2616-2624. 10.1093/annonc/mdr489.CrossRefPubMedPubMedCentral
41.
Dienstmann R, Serpico D, Rodon J, Saura C, Macarulla T, Elez E, Alsina M, Capdevila J, Perez-Garcia J, Sánchez-Ollé G, Aura C, Prudkin L, Landolfi S, Hernández-Losa J, Vivancos A, Tabernero J: Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials. Mol Cancer Ther. 2012, 11: 2062-2071. 10.1158/1535-7163.MCT-12-0290.CrossRefPubMed
42.
Tran B, Brown AM, Bedard PL, Winquist E, Goss GD, Hotte SJ, Welch SA, Hirte HW, Zhang T, Stein LD, Ferretti V, Watt S, Jiao W, Ng K, Ghai S, Shaw P, Petrocelli T, Hudson TJ, Neel BG, Onetto N, Siu LL, McPherson JD, Kamel-Reid S, Dancey JE: Feasibility of real time next generation sequencing of cancer genes linked to drug response: results from a clinical trial. Int J Cancer. 2013, 132: 1547-1555. 10.1002/ijc.27817.CrossRefPubMed
43.
Wagle N, Berger MF, Davis MJ, Blumenstiel B, DeFelice M, Pochanard P, Ducar M, Van Hummelen P, MacConaill LE, Hahn WC: High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov. 2012, 2: 82-93. 10.1158/2159-8290.CD-11-0184.CrossRefPubMed
44.
Roychowdhury S, Iyer MK, Robinson DR, Lonigro RJ, Wu YM, Cao X, Kalyana-Sundaram S, Sam L, Balbin OA, Quist MJ, Barrette T, Everett J, Siddiqui J, Kunju LP, Navone N, Araujo JC, Troncoso P, Logothetis CJ, Innis JW, Smith DC, Lao CD, Kim SY, Roberts JS, Gruber SB, Pienta KJ, Talpaz M, Chinnaiyan AM: Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med. 2011, 3: 111ra121-10.1126/scitranslmed.3003161.CrossRefPubMedPubMedCentral
45.
Ross JS, Downing S, Yelensky R, Lipson D, Otto G, Palmer GA, Ali SM, Miller VA, Stephens P: Use of the FoundationOne next-generation sequencing (NGS) assay to detect actionable alterations leading to clinical benefit of targeted therapies for relapsed and refractory breast cancer. J Clin Oncol. 2013, 31: abstr 1009-CrossRef
46.
Lipson D, He J, Yelensky R, Miller V, Sheehan C, Brennan K, Stephens P, Cronin M, Ross J: Next-generation sequencing of FFPE breast cancers demonstrates high concordance with FISH in calling HER2 amplifications and commonly identifies additional clinically relevant genomic alterations. Cancer Res. 2012, 72: 1730-1731. 10.1158/1538-7445.AM2012-1730.CrossRef
47.
Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW: Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012, 18: 382-384. 10.1038/nm.2673.CrossRefPubMedPubMedCentral
48.
Tuma RS: Large-scale genome projects enter the clinic on both sides of the Atlantic. J Natl Cancer Inst. 2011, 103: 1730-1731. 10.1093/jnci/djr503.CrossRefPubMed
49.
Hollebecque A, Massard C, De Baere T, Auger N, Lacroix L, Koubi-Pick V, Vielh P, Lazar V, Bahleda R, Ngo-camus M, Angevin E, Varga A, Deschamps F, Gazzah A, Mazoyer C, Richon C, Vassal G, Eggermont AM, Andre F, Soria JC: Molecular screening for cancer treatment optimization (MOSCATO 01): a prospective molecular triage trial—Interim results. J Clin Oncol. 2013, 31: abstr 2512-
50.
Andre F, Bachelot TD, Campone M, Arnedos M, Dieras V, Lacroix-Triki M, Lazar V, Gentien D, Cohen P, Goncalves A, Lacroix L, Chaffanet M, Dalenc F, Mathieu MC, Bieche I, Olschwang S, Wang Q, Commo F, Jimenez M, Bonnefoi HR: Array CGH and DNA sequencing to personalize targeted treatment of metastatic breast cancer (MBC) patients (pts): a prospective multicentric trial (SAFIR01). J Clin Oncol. 2013, 31: abstr 511-CrossRef
51.
Aldridge S: 9,000 tumors for stratified medicine. Nat Biotechnol. 2011, 29: 854-854.CrossRef
Metadata
Title
Clinical application of high-throughput genomic technologies for treatment selection in breast cancer
Authors
Aaron R Hansen
Philippe L Bedard
Publication date
01-10-2013
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3558

Other articles of this Issue 5/2013

Breast Cancer Research 5/2013 Go to the issue

Research article

A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model

Research article

Pre-diagnosis oophorectomy, estrogen therapy and mortality in a cohort of women diagnosed with breast cancer

Editorial

Help us find the cures

Research article

Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development

Research article

Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women

Research article

The presence and prognostic impact of apoptotic and nonapoptotic disseminated tumor cells in the bone marrow of primary breast cancer patients after neoadjuvant chemotherapy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits