. 2009 Jun;13(2).
doi: 10.2165/01250444-200913020-00002.

Genomic predictors of outcome and treatment response in breast cancer

Lara Dunn 1 Angela Demichele  
  • PMID: 19537843
  •     62 References
  •     15 citations


Despite advances in breast cancer treatment and outcome over the last two decades, women continue to relapse and die of advanced disease. Historically, estrogen and progesterone receptor expression, HER2 overexpression and clinico-pathologic parameters have guided therapeutic decision making. However, there are limits to the risk estimation provided by these parameters, leading to potential overtreatment of low-risk disease and undertreatment of poor-risk disease. Genomic technologies now provide the opportunity to refine our therapeutic approach by individualizing treatment to patients' individual tumor profiles. Gene profiles or signatures are groupings of genes that are differentially expressed between tumors, reflecting differences in biologic behavior. Prognostic gene signatures stratify breast cancer patients by tumor natural history, regardless of the treatment employed. Currently, there are three commercially available prognostic gene signatures: Oncotype DX (Genomic Health, Inc.), MammaPrint (Agendia BV), and the HOXB13/IL17BR (H/I) ratio; (Theros H/ISM; bioTheranostics). Others under development include the Intrinsic Gene Set, the Rotterdam Signature, the Wound Response Indicator, and the Invasive Gene Signature. Predicative signatures classify patients based on responsiveness to specific therapies. Of the prognostic signatures, Oncotype DX has been shown to have predictive value for the incremental benefit of chemotherapy when added to a hormonal therapy regimen. Additional genetic profiles under development predict response to specific hormonal therapies, anthracyclines, and taxanes. Gene signatures have the potential to transform breast cancer treatment as it becomes tailored to each patient's tumor expression profile and significantly improve the outcomes of this disease.

c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer.
H B Muss, A D Thor, +7 authors, M Barcos.
N Engl J Med, 1994 May 05; 330(18). PMID: 7908410
Highly Cited.
Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer.
S Paik, R Hazan, +6 authors, C R King.
J Clin Oncol, 1990 Jan 01; 8(1). PMID: 1967301
Highly Cited.
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
Martine J Piccart-Gebhart, Marion Procter, +30 authors, Herceptin Adjuvant (HERA) Trial Study Team.
N Engl J Med, 2005 Oct 21; 353(16). PMID: 16236737
Highly Cited.
The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer.
Xiao-Jun Ma, Susan G Hilsenbeck, +6 authors, Mark G Erlander.
J Clin Oncol, 2006 Sep 30; 24(28). PMID: 17008703
Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival.
Howard Y Chang, Dimitry S A Nuyten, +10 authors, Marc J van de Vijver.
Proc Natl Acad Sci U S A, 2005 Feb 11; 102(10). PMID: 15701700    Free PMC article.
Highly Cited.
The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG).
I Balslev, C K Axelsson, +3 authors, H T Mouridsen.
Breast Cancer Res Treat, 1994 Jan 01; 32(3). PMID: 7865856
Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.
Charles L Vogel, Melody A Cobleigh, +10 authors, Michael Press.
J Clin Oncol, 2002 Feb 01; 20(3). PMID: 11821453
Highly Cited.
Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series.
Christine Desmedt, Fanny Piette, +18 authors, TRANSBIG Consortium.
Clin Cancer Res, 2007 Jun 05; 13(11). PMID: 17545524
Highly Cited.
Limits of predictive models using microarray data for breast cancer clinical treatment outcome.
James F Reid, Lara Lusa, +5 authors, Marco A Pierotti.
J Natl Cancer Inst, 2005 Jun 16; 97(12). PMID: 15956654
Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy.
L N Harris, V Liotcheva, +10 authors, R C Bentley.
J Clin Oncol, 2001 Mar 17; 19(6). PMID: 11250999
Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer.
G M Clark, C K Osborne, W L McGuire.
J Clin Oncol, 1984 Oct 01; 2(10). PMID: 6491696
Highly Cited.
erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer.
S Paik, J Bryant, +7 authors, N Wolmark.
J Natl Cancer Inst, 1998 Sep 25; 90(18). PMID: 9747867
Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.
Marc Buyse, Sherene Loi, +18 authors, TRANSBIG Consortium.
J Natl Cancer Inst, 2006 Sep 07; 98(17). PMID: 16954471
Highly Cited.
Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer.
Juliane Hannemann, Hendrika M Oosterkamp, +6 authors, Marc J van de Vijver.
J Clin Oncol, 2005 May 24; 23(15). PMID: 15908647
HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15.
S Paik, J Bryant, +4 authors, N Wolmark.
J Natl Cancer Inst, 2000 Dec 21; 92(24). PMID: 11121461
A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.
Laurel A Habel, Steven Shak, +12 authors, Charles P Quesenberry.
Breast Cancer Res, 2006 Jun 02; 8(3). PMID: 16737553    Free PMC article.
Highly Cited.
Molecular portraits of human breast tumours.
C M Perou, T Sørlie, +15 authors, D Botstein.
Nature, 2000 Aug 30; 406(6797). PMID: 10963602
Highly Cited.
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D J Slamon, G M Clark, +3 authors, W L McGuire.
Science, 1987 Jan 09; 235(4785). PMID: 3798106
Highly Cited.
Gene expression profiling predicts clinical outcome of breast cancer.
Laura J van 't Veer, Hongyue Dai, +13 authors, Stephen H Friend.
Nature, 2002 Feb 02; 415(6871). PMID: 11823860
Highly Cited.
The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes.
Lisa A Carey, E Claire Dees, +7 authors, Charles M Perou.
Clin Cancer Res, 2007 Apr 18; 13(8). PMID: 17438091
Highly Cited.
Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
Edward H Romond, Edith A Perez, +22 authors, Norman Wolmark.
N Engl J Med, 2005 Oct 21; 353(16). PMID: 16236738
Highly Cited.
International Agency for Research on Cancer workshop on 'Expression array analyses in breast cancer taxonomy'.
Sean V Tavtigian, Marco A Pierotti, Anne-Lise Børresen-Dale.
Breast Cancer Res, 2006 Nov 14; 8(6). PMID: 17096863    Free PMC article.
The prognostic role of a gene signature from tumorigenic breast-cancer cells.
Rui Liu, Xinhao Wang, +7 authors, Michael F Clarke.
N Engl J Med, 2007 Jan 19; 356(3). PMID: 17229949
Highly Cited.
Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients.
Jenny C Chang, Eric C Wooten, +12 authors, Peter O'Connell.
J Clin Oncol, 2005 Feb 19; 23(6). PMID: 15718313
Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue.
Lida Mina, Sharon E Soule, +8 authors, Kathy D Miller.
Breast Cancer Res Treat, 2006 Oct 14; 103(2). PMID: 17039265
Gene expression profile and angiogenic marker correlates with response to neoadjuvant bevacizumab followed by bevacizumab plus chemotherapy in breast cancer.
Sherry X Yang, Seth M Steinberg, +3 authors, Sandra M Swain.
Clin Cancer Res, 2008 Sep 17; 14(18). PMID: 18794102    Free PMC article.
Repeated observation of breast tumor subtypes in independent gene expression data sets.
Therese Sorlie, Robert Tibshirani, +13 authors, David Botstein.
Proc Natl Acad Sci U S A, 2003 Jun 28; 100(14). PMID: 12829800    Free PMC article.
Highly Cited.
Trial assessing individualized options for treatment for breast cancer: the TAILORx trial.
Jo Anne Zujewski, Leah Kamin.
Future Oncol, 2008 Oct 17; 4(5). PMID: 18922117
Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients.
Jenny C Chang, Andreas Makris, +14 authors, Steven Shak.
Breast Cancer Res Treat, 2007 May 01; 108(2). PMID: 17468949
Gene expression profiles of multiple breast cancer phenotypes and response to neoadjuvant chemotherapy.
Holly K Dressman, Christopher Hans, +11 authors, Kimberly Blackwell.
Clin Cancer Res, 2006 Feb 10; 12(3 Pt 1). PMID: 16467094
Concordance among gene-expression-based predictors for breast cancer.
Cheng Fan, Daniel S Oh, +5 authors, Charles M Perou.
N Engl J Med, 2006 Aug 11; 355(6). PMID: 16899776
Highly Cited.
Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.
Aman U Buzdar, Nuhad K Ibrahim, +17 authors, Gabriel N Hortobagyi.
J Clin Oncol, 2005 Mar 02; 23(16). PMID: 15738535
Highly Cited.
An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer.
Kelly H Salter, Chaitanya R Acharya, +11 authors, Anil Potti.
PLoS One, 2008 Apr 03; 3(4). PMID: 18382681    Free PMC article.
Molecular-cytogenetic analysis of HER-2/neu gene in BRCA1-associated breast cancers.
Tatyana A Grushko, M Anne Blackwood, +6 authors, Olufunmilayo I Olopade.
Cancer Res, 2002 Mar 13; 62(5). PMID: 11888924
Exploring the two-gene ratio in breast cancer--independent roles for HOXB13 and IL17BR in prediction of clinical outcome.
Piiha-Lotta Jerevall, Sara Brommesson, +7 authors, Olle Stål.
Breast Cancer Res Treat, 2007 Apr 25; 107(2). PMID: 17453342
Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.
Luca Gianni, Milvia Zambetti, +14 authors, Steven Shak.
J Clin Oncol, 2005 Sep 08; 23(29). PMID: 16145055
Highly Cited.
A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen.
Xiao-Jun Ma, Zuncai Wang, +27 authors, Dennis C Sgroi.
Cancer Cell, 2004 Jun 15; 5(6). PMID: 15193263
Highly Cited.
Meeting highlights: International Consensus Panel on the Treatment of Primary Breast Cancer. Seventh International Conference on Adjuvant Therapy of Primary Breast Cancer.
A Goldhirsch, J H Glick, +2 authors, H J Senn.
J Clin Oncol, 2001 Sep 18; 19(18). PMID: 11559719
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Prediction of docetaxel response in human breast cancer by gene expression profiling.
Kyoko Iwao-Koizumi, Ryo Matoba, +6 authors, Kikuya Kato.
J Clin Oncol, 2005 Jan 22; 23(3). PMID: 15659489
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.
Yixin Wang, Jan G M Klijn, +11 authors, John A Foekens.
Lancet, 2005 Feb 22; 365(9460). PMID: 15721472
Highly Cited.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
Jenny C Chang, Eric C Wooten, +8 authors, Peter O'Connell.
Lancet, 2003 Aug 09; 362(9381). PMID: 12907009
Highly Cited.
Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.
M Ayers, W F Symmans, +15 authors, L Pusztai.
J Clin Oncol, 2004 May 12; 22(12). PMID: 15136595
Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistance.
Matthew P Goetz, Vera J Suman, +12 authors, James N Ingle.
Clin Cancer Res, 2008 Sep 17; 14(18). PMID: 18794098    Free PMC article.
Multicenter validation of a gene expression-based prognostic signature in lymph node-negative primary breast cancer.
John A Foekens, David Atkins, +17 authors, Yixin Wang.
J Clin Oncol, 2006 Mar 01; 24(11). PMID: 16505412
HOXB13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study.
Maurice P H M Jansen, Anieta M Sieuwerts, +6 authors, Els M J J Berns.
J Clin Oncol, 2007 Feb 20; 25(6). PMID: 17308270
Predictors of primary breast cancers responsiveness to preoperative epirubicin/cyclophosphamide-based chemotherapy: translation of microarray data into clinically useful predictive signatures.
Olga Modlich, Hans-Bernd Prisack, +2 authors, Hans Bojar.
J Transl Med, 2005 Aug 11; 3. PMID: 16091131    Free PMC article.
A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen.
Matthew P Goetz, Vera J Suman, +9 authors, Fergus J Couch.
Clin Cancer Res, 2006 Apr 13; 12(7 Pt 1). PMID: 16609019
Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer.
William D Foulkes, Ingunn M Stefansson, +5 authors, Lars A Akslen.
J Natl Cancer Inst, 2003 Oct 02; 95(19). PMID: 14519755
Highly Cited.
Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial.
Hervé Bonnefoi, Anil Potti, +16 authors, Richard D Iggo.
Lancet Oncol, 2007 Nov 21; 8(12). PMID: 18024211
Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA.
M J van de Vijver, W J Mooi, +2 authors, R Nusse.
Oncogene, 1988 Feb 01; 2(2). PMID: 3285295
Prospective identification of tumorigenic breast cancer cells.
Muhammad Al-Hajj, Max S Wicha, +2 authors, Michael F Clarke.
Proc Natl Acad Sci U S A, 2003 Mar 12; 100(7). PMID: 12629218    Free PMC article.
Highly Cited.
Staging system for breast cancer: revisions for the 6th edition of the AJCC Cancer Staging Manual.
S Eva Singletary, Craig Allred, +17 authors, Frederick L Greene.
Surg Clin North Am, 2003 Jul 24; 83(4). PMID: 12875597
A gene-expression signature as a predictor of survival in breast cancer.
Marc J van de Vijver, Yudong D He, +18 authors, René Bernards.
N Engl J Med, 2002 Dec 20; 347(25). PMID: 12490681
Highly Cited.
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 May 17; 365(9472). PMID: 15894097
Highly Cited.
Breast cancer molecular subtypes respond differently to preoperative chemotherapy.
Roman Rouzier, Charles M Perou, +13 authors, Lajos Pusztai.
Clin Cancer Res, 2005 Aug 24; 11(16). PMID: 16115903
Highly Cited.
Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer.
Chaitanya R Acharya, David S Hsu, +15 authors, Anil Potti.
JAMA, 2008 Apr 05; 299(13). PMID: 18387932
Gene expression patterns for doxorubicin (Adriamycin) and cyclophosphamide (cytoxan) (AC) response and resistance.
Susan Cleator, Anna Tsimelzon, +8 authors, Jenny C Chang.
Breast Cancer Res Treat, 2005 Dec 03; 95(3). PMID: 16322899
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
T Sørlie, C M Perou, +14 authors, A L Børresen-Dale.
Proc Natl Acad Sci U S A, 2001 Sep 13; 98(19). PMID: 11553815    Free PMC article.
Highly Cited.
Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.
Lori J Goldstein, Robert Gray, +12 authors, Joseph A Sparano.
J Clin Oncol, 2008 Aug 06; 26(25). PMID: 18678838    Free PMC article.
Highly Cited.
Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.
Lisa A Carey, Charles M Perou, +14 authors, Robert C Millikan.
JAMA, 2006 Jun 08; 295(21). PMID: 16757721
Highly Cited.
Renal cell carcinoma: where will the state-of-the-art lead us?
A Rose Brannon, W Kimryn Rathmell.
Curr Oncol Rep, 2010 Apr 29; 12(3). PMID: 20425079    Free PMC article.
Proteomics and ovarian cancer: integrating proteomics information into clinical care.
John L Hays, Geoffrey Kim, Iulia Giuroiu, Elise C Kohn.
J Proteomics, 2010 Jun 22; 73(10). PMID: 20561909    Free PMC article.
Proteomics as a guiding tool for more effective personalized therapy.
J-M Lee, E C Kohn.
Ann Oncol, 2010 Oct 15; 21 Suppl 7. PMID: 20943616    Free PMC article.
Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis.
Robert H Goldstein, Michaela R Reagan, +2 authors, Michael Rosenblatt.
Cancer Res, 2010 Dec 17; 70(24). PMID: 21159629    Free PMC article.
The pro-metastatic role of bone marrow-derived cells: a focus on MSCs and regulatory T cells.
Bong Ihn Koh, Yibin Kang.
EMBO Rep, 2012 Apr 05; 13(5). PMID: 22473297    Free PMC article.
Pathological complete response in younger and older breast cancer patients.
Agnieszka Kołacińska, Justyna Chałubińska, +4 authors, Zbigniew Morawiec.
Arch Med Sci, 2012 Jun 05; 8(2). PMID: 22662005    Free PMC article.
HER2/neu protein expression and fine needle breast aspiration from Argentinean patients with non-palpable breast lesions.
Wendy Gabriela Domínguez, Héctor Nardi, +3 authors, Gabriela Andrea Balogh.
Exp Ther Med, 2010 Jul 01; 1(4). PMID: 22993582    Free PMC article.
A tale of mice and (wo)men: development of and insights from an "all human" animal model of breast cancer metastasis to bone.
Michael Rosenblatt.
Trans Am Clin Climatol Assoc, 2013 Jan 11; 123. PMID: 23303981    Free PMC article.
The metastasis-promoting roles of tumor-associated immune cells.
Heath A Smith, Yibin Kang.
J Mol Med (Berl), 2013 Mar 22; 91(4). PMID: 23515621    Free PMC article.
Highly Cited. Review.
The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis.
Josh J Carlson, Joshua A Roth.
Breast Cancer Res Treat, 2013 Aug 27; 141(1). PMID: 23974828    Free PMC article.
Highly Cited. Systematic Review.
Integrated genomic analysis of breast cancers.
L Addou-Klouche, J Adélaïde, +8 authors, M Chaffanet.
Balkan J Med Genet, 2013 Sep 21; 15(Suppl). PMID: 24052748    Free PMC article.
Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.
Stéphanie Cornen, Arnaud Guille, +16 authors, Max Chaffanet.
PLoS One, 2014 Jan 15; 9(1). PMID: 24416132    Free PMC article.
Proteomics of ovarian cancer: functional insights and clinical applications.
Mohamed A Elzek, Karin D Rodland.
Cancer Metastasis Rev, 2015 Mar 05; 34(1). PMID: 25736266    Free PMC article.
Analysis of gene expression profiles as a tool to uncover tumor markers of liver cancer progression in a rat model.
Verónica R Vásquez-Garzón, Olga Beltrán-Ramírez, +2 authors, Saúl Villa-Treviño.
Biomed Rep, 2015 Mar 24; 3(2). PMID: 25798242    Free PMC article.
Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in a mouse Xenograft model.
Jia-Jia Li, Wei-Ling Chen, +5 authors, Xiang-Hui Han.
Acta Pharmacol Sin, 2017 Apr 18; 38(10). PMID: 28414206    Free PMC article.