Journal Article
. 2013 Jan;6(3-4).

Modern Risk Assessment for Individualizing Treatment Concepts in Early-stage Breast Cancer

Alex Farr 1 Rachel Wuerstlein 2 Annika Heiduschka 3 Christian F Singer 1 Nadia Harbeck 3 
Affiliations
  • PMID: 24920978
  •     72 References
  •     2 citations

Abstract

Validated prognostic and predictive factors currently play an important role in treatment planning for patients with early-stage breast cancer. The role of personalized medicine has led to the search for markers that can be applied to individual patients to optimize treatment regimens. In addition to traditional clinicopathologic measures, scores and gene tests have been developed to independently predict risk of patients in the neoadjuvant and adjuvant settings. The discovery of these markers provides the opportunity to identify patients at such low risk of recurrence that toxic therapy side effects are not justified. Selection and management of patients with early-stage, hormone receptor-positive breast cancer who are appropriately treated with endocrine therapy alone after receiving locoregional therapy but do not necessarily require adjuvant chemotherapy is currently problematic. This article reviews the current state-of-theart biomarker assessment methods and discusses the potential role for the prediction of chemotherapy benefit focusing on endocrine sensitive disease.

Keywords: Biomarkers; Breast cancer; Gene tests; Neoadjuvant; Prediction.

Other Links

Free PMC article 
Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial.
Jack Cuzick, Ivana Sestak, +5 authors, ATAC/LATTE investigators.
Lancet Oncol, 2010 Nov 23; 11(12). PMID: 21087898
Highly Cited.
Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation.
J Gerdes, U Schwab, H Lemke, H Stein.
Int J Cancer, 1983 Jan 15; 31(1). PMID: 6339421
Highly Cited.
Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort.
Ben S Wittner, Dennis C Sgroi, +9 authors, Sridhar Ramaswamy.
Clin Cancer Res, 2008 May 17; 14(10). PMID: 18483364    Free PMC article.
Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20.
Gong Tang, Steven Shak, +6 authors, Norman Wolmark.
Breast Cancer Res Treat, 2011 Jan 12; 127(1). PMID: 21221771    Free PMC article.
Effect of local or systemic treatment prior to primary tumor removal on the production and response to a serum growth-stimulating factor in mice.
B Fisher, E Saffer, +2 authors, N Gunduz.
Cancer Res, 1989 Apr 15; 49(8). PMID: 2522814
Commercialized multigene predictors of clinical outcome for breast cancer.
Jeffrey S Ross, Christos Hatzis, +2 authors, Gabriel N Hortobágyi.
Oncologist, 2008 Jun 03; 13(5). PMID: 18515733
Review.
Adjuvant trastuzumab in HER2-positive breast cancer.
Dennis Slamon, Wolfgang Eiermann, +21 authors, Breast Cancer International Research Group.
N Engl J Med, 2011 Oct 14; 365(14). PMID: 21991949    Free PMC article.
Highly Cited.
Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute.
G Bonadonna, P Valagussa, +4 authors, M Zambetti.
J Clin Oncol, 1998 Jan 24; 16(1). PMID: 9440728
Highly Cited.
Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial.
Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, John F Forbes, +4 authors, Michael Baum.
Lancet Oncol, 2007 Dec 18; 9(1). PMID: 18083636
Highly Cited.
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.
The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age.
S Mook, M K Schmidt, +7 authors, L J van 't Veer.
Ann Oncol, 2009 Oct 15; 21(4). PMID: 19825882
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.
Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study.
Mitch Dowsett, Jack Cuzick, +11 authors, Steven Shak.
J Clin Oncol, 2010 Mar 10; 28(11). PMID: 20212256
Highly Cited.
A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors.
Martin Filipits, Margaretha Rudas, +25 authors, EP Investigators.
Clin Cancer Res, 2011 Aug 03; 17(18). PMID: 21807638
Highly Cited.
Decentral gene expression analysis for ER+/Her2- breast cancer: results of a proficiency testing program for the EndoPredict assay.
Carsten Denkert, Ralf Kronenwett, +23 authors, Manfred Dietel.
Virchows Arch, 2012 Mar 01; 460(3). PMID: 22371223    Free PMC article.
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.
Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer.
BIG 1-98 Collaborative Group, Henning Mouridsen, +10 authors, Alan S Coates.
N Engl J Med, 2009 Aug 21; 361(8). PMID: 19692688    Free PMC article.
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.
American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.
Antonio C Wolff, M Elizabeth H Hammond, +22 authors, College of American Pathologists.
J Clin Oncol, 2006 Dec 13; 25(1). PMID: 17159189
Highly Cited.
The molecular portraits of breast tumors are conserved across microarray platforms.
Zhiyuan Hu, Cheng Fan, +28 authors, Charles M Perou.
BMC Genomics, 2006 Apr 29; 7. PMID: 16643655    Free PMC article.
Highly Cited.
Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group.
Lancet, 1998 May 30; 351(9114). PMID: 9605801
Highly Cited.
Cost effectiveness of gene expression profiling for early stage breast cancer: a decision-analytic model.
Mo Yang, Suja Rajan, Amalia M Issa.
Cancer, 2012 Feb 24; 118(20). PMID: 22359236
Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer.
Jack Cuzick, Mitch Dowsett, +10 authors, John F Forbes.
J Clin Oncol, 2011 Oct 13; 29(32). PMID: 21990413
Highly Cited.
uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial.
K Annecke, M Schmitt, +6 authors, N Harbeck.
Adv Clin Chem, 2008 Apr 24; 45. PMID: 18429492
Review.
Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER).
Jolien M Bueno-de-Mesquita, Wim H van Harten, +19 authors, Sabine C Linn.
Lancet Oncol, 2007 Nov 29; 8(12). PMID: 18042430
Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women.
Christine M Friedenreich, Christy G Woolcott, +14 authors, Kerry S Courneya.
J Clin Oncol, 2010 Feb 18; 28(9). PMID: 20159820    Free PMC article.
Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18.
N Wolmark, J Wang, +2 authors, B Fisher.
J Natl Cancer Inst Monogr, 2002 Jan 05; (30). PMID: 11773300
Highly Cited.
Lost in translation? Estrogen receptor status and endocrine responsiveness in breast cancer.
Nadia Harbeck, Achim Rody.
J Clin Oncol, 2012 Feb 01; 30(7). PMID: 22291083
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.
American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.
Lyndsay Harris, Herbert Fritsche, +7 authors, American Society of Clinical Oncology.
J Clin Oncol, 2007 Oct 24; 25(33). PMID: 17954709
Highly Cited. Review.
Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer.
Nadia Harbeck, Roanld E Kates, +6 authors, John A Foekens.
Clin Breast Cancer, 2004 Dec 09; 5(5). PMID: 15585071
Review.
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.
Ian E Smith, Mitch Dowsett, +8 authors, IMPACT Trialists Group.
J Clin Oncol, 2005 Jul 07; 23(22). PMID: 15998903
Highly Cited.
Breast cancer classification and prognosis based on gene expression profiles from a population-based study.
Christos Sotiriou, Soek-Ying Neo, +7 authors, Edison T Liu.
Proc Natl Acad Sci U S A, 2003 Aug 15; 100(18). PMID: 12917485    Free PMC article.
Highly Cited.
Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.
Kathy S Albain, William E Barlow, +18 authors, Breast Cancer Intergroup of North America.
Lancet, 2009 Dec 17; 374(9707). PMID: 20004966    Free PMC article.
Systematic review: gene expression profiling assays in early-stage breast cancer.
Luigi Marchionni, Renee F Wilson, +4 authors, Steven N Goodman.
Ann Intern Med, 2008 Feb 07; 148(5). PMID: 18252678
Systematic Review.
Calibration and discriminatory accuracy of prognosis calculation for breast cancer with the online Adjuvant! program: a hospital-based retrospective cohort study.
Stella Mook, Marjanka K Schmidt, +6 authors, Peter M Ravdin.
Lancet Oncol, 2009 Oct 06; 10(11). PMID: 19801202
Ten-year analysis of the prospective multicentre Chemo-N0 trial validates American Society of Clinical Oncology (ASCO)-recommended biomarkers uPA and PAI-1 for therapy decision making in node-negative breast cancer patients.
N Harbeck, M Schmitt, +12 authors, Chemo-N 0 Study Group.
Eur J Cancer, 2013 Mar 16; 49(8). PMID: 23490655
Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group.
Lancet, 1998 Sep 30; 352(9132). PMID: 9752815
Highly Cited.
Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031.
Matthew J Ellis, Vera J Suman, +17 authors, John A Olson.
J Clin Oncol, 2011 May 11; 29(17). PMID: 21555689    Free PMC article.
Highly Cited.
Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer.
Catherine L Harper-Wynne, Nigel P M Sacks, +14 authors, Mitchell Dowsett.
J Clin Oncol, 2002 Feb 15; 20(4). PMID: 11844826
Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting.
J U Blohmer, M Rezai, +6 authors, W Eiermann.
J Med Econ, 2012 Sep 13; 16(1). PMID: 22966753
Cost-effectiveness of 70-gene MammaPrint signature in node-negative breast cancer.
Er Chen, Kuo Bianchini Tong, Jennifer L Malin.
Am J Manag Care, 2011 Feb 05; 16(12). PMID: 21291290
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.
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.
Population-based validation of the prognostic model ADJUVANT! for early breast cancer.
Ivo A Olivotto, Chris D Bajdik, +6 authors, Karen A Gelmon.
J Clin Oncol, 2005 Apr 20; 23(12). PMID: 15837986
Highly Cited.
Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival.
Mitch Dowsett, Ian E Smith, +11 authors, IMPACT Trialists.
Clin Cancer Res, 2005 Feb 11; 11(2 Pt 2). PMID: 15701892
The MINDACT trial: the first prospective clinical validation of a genomic tool.
Fatima Cardoso, Martine Piccart-Gebhart, +2 authors, TRANSBIG Consortium.
Mol Oncol, 2007 Dec 01; 1(3). PMID: 19383299    Free PMC article.
Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade.
Sherene Loi, Benjamin Haibe-Kains, +14 authors, Christos Sotiriou.
J Clin Oncol, 2007 Apr 03; 25(10). PMID: 17401012
Highly Cited.
Validation of 70-gene prognosis signature in node-negative breast cancer.
J M Bueno-de-Mesquita, S C Linn, +16 authors, M J van de Vijver.
Breast Cancer Res Treat, 2008 Sep 27; 117(3). PMID: 18819002
Gene-expression signatures in breast cancer.
Christos Sotiriou, Lajos Pusztai.
N Engl J Med, 2009 Feb 21; 360(8). PMID: 19228622
Highly Cited. Review.
First-generation genomic tests for breast cancer treatment.
Fabrice Andre, Suzette Delaloge.
Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005177
The EORTC 10041/BIG 03-04 MINDACT trial is feasible: results of the pilot phase.
Emiel Rutgers, Martine J Piccart-Gebhart, +12 authors, Fatima Cardoso.
Eur J Cancer, 2011 Nov 05; 47(18). PMID: 22051734
Estrogen receptors and human disease.
Bonnie J Deroo, Kenneth S Korach.
J Clin Invest, 2006 Mar 03; 116(3). PMID: 16511588    Free PMC article.
Highly Cited. Review.
Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics.
Matthew J Ellis, Yu Tao, +9 authors, Mitch Dowsett.
J Natl Cancer Inst, 2008 Sep 25; 100(19). PMID: 18812550    Free PMC article.
Highly Cited.
Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer.
Mitch Dowsett, Ian E Smith, +8 authors, IMPACT Trialists Group.
J Natl Cancer Inst, 2007 Jan 18; 99(2). PMID: 17228000
Highly Cited.
International Web-based consultation on priorities for translational breast cancer research.
Mitch Dowsett, Aron Goldhirsch, +3 authors, Giuseppe Viale.
Breast Cancer Res, 2007 Nov 24; 9(6). PMID: 18034879    Free PMC article.
Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.
Christos Sotiriou, Pratyaksha Wirapati, +17 authors, Mauro Delorenzi.
J Natl Cancer Inst, 2006 Feb 16; 98(4). PMID: 16478745
Highly Cited.
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.
The molecular and cellular biology of HER2/neu gene amplification/overexpression and the clinical development of herceptin (trastuzumab) therapy for breast cancer.
M D Pegram, G Konecny, D J Slamon.
Cancer Treat Res, 2000 Aug 19; 103. PMID: 10948442
Review.
Assessment of the contribution of the IHC4+C score to decision making in clinical practice in early breast cancer.
S Barton, L Zabaglo, +6 authors, M Dowsett.
Br J Cancer, 2012 Apr 26; 106(11). PMID: 22531639    Free PMC article.
Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.
Kathy S Albain, William E Barlow, +20 authors, Breast Cancer Intergroup of North America.
Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005174    Free PMC article.
Highly Cited.
Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths.
Rebecca Siegel, Elizabeth Ward, Otis Brawley, Ahmedin Jemal.
CA Cancer J Clin, 2011 Jun 21; 61(4). PMID: 21685461
Highly Cited.
Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer.
P M Ravdin, L A Siminoff, +4 authors, H L Parker.
J Clin Oncol, 2001 Feb 22; 19(4). PMID: 11181660
Highly Cited.
Clinical application of the 70-gene profile: the MINDACT trial.
Fatima Cardoso, Laura Van't Veer, +3 authors, Martine J Piccart-Gebhart.
J Clin Oncol, 2008 Feb 09; 26(5). PMID: 18258980
Highly Cited.
Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment.
Peter A Fasching, Katharina Heusinger, +14 authors, David L Wachter.
BMC Cancer, 2011 Nov 16; 11. PMID: 22081974    Free PMC article.
Highly Cited.
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.
A computer based program to assist in adjuvant therapy decisions for individual breast cancer patients.
P M Ravdin.
Bull Cancer, 1995 Dec 01; 82 Suppl 5. PMID: 8680066
American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.
M Elizabeth H Hammond, Daniel F Hayes, +29 authors, Antonio C Wolff.
J Clin Oncol, 2010 Apr 21; 28(16). PMID: 20404251    Free PMC article.
Highly Cited. Systematic Review.
Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status.
Matthew J Ellis, Andrew Coop, +8 authors, William R Miller.
Cancer Res, 2003 Oct 16; 63(19). PMID: 14559846
Endocrine therapy, new biologicals, and new study designs for presurgical studies in breast cancer.
Mitch Dowsett, Ian Smith, +13 authors, Judith Bliss.
J Natl Cancer Inst Monogr, 2011 Nov 02; 2011(43). PMID: 22043057
Multimodal treatment for locally advanced breast cancer. Result of chemotherapy-radiotherapy versus chemotherapy-surgery.
M De Lena, M Varini, +5 authors, G Bonadonna.
Cancer Clin Trials, 1981 Jan 01; 4(3). PMID: 7026073
A new predictive tool for postoperative radiotherapy in prostate cancer.
Daniel K Lee, William D Figg.
Cancer Biol Ther, 2017 Apr 19; 18(5). PMID: 28418285    Free PMC article.
Quantification of hypoxia-related gene expression as a potential approach for clinical outcome prediction in breast cancer.
Abderrahim El Guerrab, Anne Cayre, +5 authors, Yves-Jean Bignon.
PLoS One, 2017 Apr 22; 12(4). PMID: 28430808    Free PMC article.