Journal Article
. 2008 May;14(10).
doi: 10.1158/1078-0432.CCR-07-4723.

Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort

Ben S Wittner 1 Dennis C Sgroi  Paula D Ryan  Tako J Bruinsma  Annuska M Glas  Anitha Male  Sonika Dahiya  Karleen Habin  Rene Bernards  Daniel A Haber  Laura J Van't Veer  Sridhar Ramaswamy  
Affiliations
  • PMID: 18483364
  •     14 References
  •     47 citations

Abstract

Purpose: Most node-negative breast cancer patients are older and postmenopausal and are increasingly being offered adjuvant chemotherapy despite their low overall risk of distant relapse. A molecular diagnostic test with high negative predictive value (NPV) for distant metastasis in this subgroup would spare many older breast cancer patients adjuvant treatment.

Experimental Design: We determined the NPV and positive predictive value of the MammaPrint assay in breast cancer patients who were consecutively diagnosed and treated at the Massachusetts General Hospital between 1985 and 1997. Primary tumors from 100 patients with node-negative, invasive breast cancer (median age, 62.5 years; median follow-up, 11.3 years) were subjected to MammaPrint analysis and classified as being at either low or high risk for distant metastasis.

Results: The MammaPrint 70-gene signature displayed excellent NPV as in previous studies, correctly identifying 100% of women at low risk for distant metastases at 5 years. However, this assay had a lower positive predictive value (12% at 5 years) than previously observed.

Conclusions: The MammaPrint assay was originally designed to identify younger breast cancer patients at low risk for distant metastasis, who might consequently be spared systemic treatment. We show here that the same signature has a very high NPV for distant recurrence after adjuvant treatment in older breast cancer patients.

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.
New prognostic factors for breast cancer recurrence.
C Isaacs, V Stearns, D F Hayes.
Semin Oncol, 2001 Mar 20; 28(1). PMID: 11254867
Review.
National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1-3, 2000.
P Eifel, J A Axelson, +11 authors, D Roter.
J Natl Cancer Inst, 2001 Jul 05; 93(13). PMID: 11438563
Highly Cited. Review.
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
Review.
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.
DNA microarrays in clinical oncology.
Sridhar Ramaswamy, Todd R Golub.
J Clin Oncol, 2002 Mar 29; 20(7). PMID: 11919254
Review.
Converting a breast cancer microarray signature into a high-throughput diagnostic test.
Annuska M Glas, Arno Floore, +9 authors, Laura J Van't Veer.
BMC Genomics, 2006 Nov 01; 7. PMID: 17074082    Free PMC article.
Highly Cited.
A molecular signature of metastasis in primary solid tumors.
Sridhar Ramaswamy, Ken N Ross, Eric S Lander, Todd R Golub.
Nat Genet, 2002 Dec 07; 33(1). PMID: 12469122
Highly Cited.
DNA microarrays in breast cancer: the promise of personalised medicine.
Sridhar Ramaswamy, Charles M Perou.
Lancet, 2003 May 16; 361(9369). PMID: 12747872
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.
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.
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.
Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial.
Jan Bogaerts, Fatima Cardoso, +12 authors, TRANSBIG consortium.
Nat Clin Pract Oncol, 2006 Oct 05; 3(10). PMID: 17019432
Review.
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.
Genomancy: predicting tumour response to cancer therapy based on the oracle of genetics.
P D Williams, J K Lee, D Theodorescu.
Curr Oncol, 2009 Feb 21; 16(1). PMID: 19229372    Free PMC article.
Antiestrogen-resistant subclones of MCF-7 human breast cancer cells are derived from a common monoclonal drug-resistant progenitor.
Kathryn R Coser, Ben S Wittner, +8 authors, Toshi Shioda.
Proc Natl Acad Sci U S A, 2009 Aug 27; 106(34). PMID: 19706540    Free PMC article.
ArrayMining: a modular web-application for microarray analysis combining ensemble and consensus methods with cross-study normalization.
Enrico Glaab, Jonathan M Garibaldi, Natalio Krasnogor.
BMC Bioinformatics, 2009 Oct 30; 10. PMID: 19863798    Free PMC article.
A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics.
Yi Hong, Thomas Downey, +2 authors, Peh Yean Cheah.
Clin Exp Metastasis, 2010 Feb 10; 27(2). PMID: 20143136
Highly Cited.
Protein interaction network underpins concordant prognosis among heterogeneous breast cancer signatures.
James Chen, Lee Sam, +5 authors, Yves A Lussier.
J Biomed Inform, 2010 Mar 31; 43(3). PMID: 20350617    Free PMC article.
Gene-expression-based prognostic assays for breast cancer.
Chungyeul Kim, Soonmyung Paik.
Nat Rev Clin Oncol, 2010 May 05; 7(6). PMID: 20440284
Review.
Integrative analysis of -omics data and histologic scoring in renal disease and transplantation: renal histogenomics.
Paul Perco, Rainer Oberbauer.
Semin Nephrol, 2010 Nov 04; 30(5). PMID: 21044763    Free PMC article.
Review.
Adjuvant chemotherapy for breast cancer in older women: emerging evidence to aid in decision making.
Gretchen Kimmick.
Curr Treat Options Oncol, 2011 Jun 04; 12(3). PMID: 21638199
Review.
Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples.
Fathi Elloumi, Zhiyuan Hu, +4 authors, Melissa A Troester.
BMC Med Genomics, 2011 Jul 02; 4. PMID: 21718502    Free PMC article.
Induction of stable drug resistance in human breast cancer cells using a combinatorial zinc finger transcription factor library.
Jeongeun Lee, Andrew S Hirsh, +9 authors, Dennis C Sgroi.
PLoS One, 2011 Aug 06; 6(7). PMID: 21818254    Free PMC article.
The 70-gene prognostic signature for korean breast cancer patients.
Kuk Young Na, Ku Sang Kim, +7 authors, Yong Sik Jung.
J Breast Cancer, 2011 Aug 19; 14(1). PMID: 21847392    Free PMC article.
Agreement in risk prediction between the 21-gene recurrence score assay (Oncotype DX®) and the PAM50 breast cancer intrinsic Classifier™ in early-stage estrogen receptor-positive breast cancer.
Catherine M Kelly, Philip S Bernard, +7 authors, Lajos Pusztai.
Oncologist, 2012 Mar 16; 17(4). PMID: 22418568    Free PMC article.
The 70-Gene Signature as Prognostic Factor for Elderly Women with Hormone Receptor-Positive, HER2-Negative Breast Cancer.
Steffi Hartmann, Bernd Gerber, +2 authors, Toralf Reimer.
Breast Care (Basel), 2012 May 04; 7(1). PMID: 22553468    Free PMC article.
An "elite hacker": breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity.
Aaron Boudreau, Laura J van't Veer, Mina J Bissell.
Cell Adh Migr, 2012 Aug 07; 6(3). PMID: 22863741    Free PMC article.
Review.
Gene profiling in breast cancer.
Inge Peerlink, Kanchan Kaur, Hemant Singhal.
Indian J Surg Oncol, 2010 Jan 01; 1(1). PMID: 22930613    Free PMC article.
Prediction and prognosis: impact of gene expression profiling in personalized treatment of breast cancer patients.
Michael R Mallmann, Andrea Staratschek-Jox, +5 authors, Joachim L Schultze.
EPMA J, 2010 Sep 01; 1(3). PMID: 23199086    Free PMC article.
A prognosis classifier for breast cancer based on conserved gene regulation between mammary gland development and tumorigenesis: a multiscale statistical model.
Yingpu Tian, Baozhen Chen, +2 authors, Zhongxian Lu.
PLoS One, 2013 Apr 09; 8(4). PMID: 23565194    Free PMC article.
Molecular profiling for breast cancer: a comprehensive review.
Muaiad Kittaneh, Alberto J Montero, Stefan Glück.
Biomark Cancer, 2013 Nov 20; 5. PMID: 24250234    Free PMC article.
Review.
MammaPrint Feasibility in a Large Tertiary Urban Medical Center: An Initial Experience.
C Francisco Espinel, Shaughn Keating, +4 authors, Sheldon Feldman.
Scientifica (Cairo), 2012 Jan 01; 2012. PMID: 24278759    Free PMC article.
Multigene Assays for Classification, Prognosis, and Prediction in Breast Cancer: a Critical Review on the Background and Clinical Utility.
P Sinn, S Aulmann, +6 authors, A Schneeweiss.
Geburtshilfe Frauenheilkd, 2014 Apr 29; 73(9). PMID: 24771945    Free PMC article.
Modern Risk Assessment for Individualizing Treatment Concepts in Early-stage Breast Cancer.
Alex Farr, Rachel Wuerstlein, +2 authors, Nadia Harbeck.
Rev Obstet Gynecol, 2013 Jan 01; 6(3-4). PMID: 24920978    Free PMC article.
Genome-based risk prediction for early stage breast cancer.
Christina Adaniel, Komal Jhaveri, Adriana Heguy, Francisco J Esteva.
Oncologist, 2014 Sep 05; 19(10). PMID: 25187476    Free PMC article.
Review.
Application of a 70-Gene Expression Profile to Japanese Breast Cancer Patients.
Hideo Shimizu, Yoshiya Horimoto, +14 authors, Mitsue Saito.
Breast Care (Basel), 2015 Jul 22; 10(2). PMID: 26195940    Free PMC article.
Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential.
Claudia Cava, Gloria Bertoli, Isabella Castiglioni.
BMC Syst Biol, 2015 Sep 24; 9. PMID: 26391647    Free PMC article.
Review.
Using a gene expression signature when controversy exists regarding the indication for adjuvant systemic treatment reduces the proportion of patients receiving adjuvant chemotherapy: a nationwide study.
A Kuijer, A C M van Bommel, +7 authors, Th van Dalen.
Genet Med, 2015 Nov 20; 18(7). PMID: 26583684
Signatures of breast cancer metastasis at a glance.
George S Karagiannis, Sumanta Goswami, +2 authors, John S Condeelis.
J Cell Sci, 2016 Apr 17; 129(9). PMID: 27084578    Free PMC article.
Review.
Positive expression of miR-361-5p indicates better prognosis for breast cancer patients.
Zhi-Gang Cao, Yan-Ni Huang, +4 authors, Zhi-Min Shao.
J Thorac Dis, 2016 Aug 09; 8(7). PMID: 27499968    Free PMC article.
Improving Pathological Assessment of Breast Cancer by Employing Array-Based Transcriptome Analysis.
Zsuzsanna Mihály, Balázs Győrffy.
Microarrays (Basel), 2013 Jan 01; 2(3). PMID: 27605190    Free PMC article.
Review.
From High-Throughput Microarray-Based Screening to Clinical Application: The Development of a Second Generation Multigene Test for Breast Cancer Prognosis.
Jan C Brase, Ralf Kronenwett, +2 authors, Marcus Schmidt.
Microarrays (Basel), 2013 Jan 01; 2(3). PMID: 27605191    Free PMC article.
Review.
Hormonal Modulation of Breast Cancer Gene Expression: Implications for Intrinsic Subtyping in Premenopausal Women.
Sarah M Bernhardt, Pallave Dasari, +3 authors, Wendy V Ingman.
Front Oncol, 2016 Nov 30; 6. PMID: 27896218    Free PMC article.
Review.
Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays.
David M Hyams, Eric Schuur, +7 authors, Aníbal Nuñez De Pierro.
J Surg Oncol, 2017 Feb 18; 115(6). PMID: 28211064    Free PMC article.
Review.
Clinical utility of gene-expression signatures in early stage breast cancer.
Maryann Kwa, Andreas Makris, Francisco J Esteva.
Nat Rev Clin Oncol, 2017 Jun 01; 14(10). PMID: 28561071
Highly Cited. Review.
A long-range interactive DNA methylation marker panel for the promoters of HOXA9 and HOXA10 predicts survival in breast cancer patients.
Seong-Min Park, Eun-Young Choi, +2 authors, Youn-Jae Kim.
Clin Epigenetics, 2017 Jul 28; 9. PMID: 28748001    Free PMC article.
MammaPrint versus EndoPredict: Poor correlation in disease recurrence risk classification of hormone receptor positive breast cancer.
Andreas Bösl, Andreas Spitzmüller, +3 authors, Felix Offner.
PLoS One, 2017 Aug 30; 12(8). PMID: 28850621    Free PMC article.
TOP2A, GGH, and PECAM1 are associated with hematogenous, lymph node, and peritoneal recurrence in stage II/III gastric cancer patients enrolled in the ACTS-GC study.
Masanori Terashima, Wataru Ichikawa, +8 authors, ACTS-GC Group.
Oncotarget, 2017 Sep 17; 8(34). PMID: 28915696    Free PMC article.
Copy Number Profiling of MammaPrint™ Genes Reveals Association with the Prognosis of Breast Cancer Patients.
Areej Fatima, Fomaz Tariq, +2 authors, Farhan Haq.
J Breast Cancer, 2017 Oct 04; 20(3). PMID: 28970850    Free PMC article.
An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma.
Mitsuro Kanda, Kenta Murotani, +10 authors, Yasuhiro Kodera.
Oncotarget, 2017 Oct 21; 8(41). PMID: 29050343    Free PMC article.
Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.
Govindasamy-Muralidharan Karthik, Mattias Rantalainen, +9 authors, Johan Hartman.
BMC Cancer, 2017 Dec 01; 17(1). PMID: 29187174    Free PMC article.
A study of association of Oncotype DX recurrence score with DCE-MRI characteristics using multivariate machine learning models.
Ashirbani Saha, Michael R Harowicz, Weiyao Wang, Maciej A Mazurowski.
J Cancer Res Clin Oncol, 2018 Feb 11; 144(5). PMID: 29427210    Free PMC article.
Quantitative nuclear histomorphometry predicts oncotype DX risk categories for early stage ER+ breast cancer.
Jon Whitney, German Corredor, +6 authors, Anant Madabhushi.
BMC Cancer, 2018 Jun 01; 18(1). PMID: 29848291    Free PMC article.
Gene Expression Detection Assay for Cancer Clinical Use.
Shavira Narrandes, Wayne Xu.
J Cancer, 2018 Jul 22; 9(13). PMID: 30026820    Free PMC article.
Review.
Relationships of protein biomarkers of the urokinase plasminogen activator system with expression of their cognate genes in primary breast carcinomas.
Seth B Sereff, Michael W Daniels, James L Wittliff.
J Clin Lab Anal, 2019 Jul 31; 33(9). PMID: 31359505    Free PMC article.
Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data.
Limei Wang, Jin Li, +9 authors, Lang Li.
Genes (Basel), 2019 Sep 29; 10(10). PMID: 31557971    Free PMC article.
GABRQ expression is a potential prognostic marker for patients with clear cell renal cell carcinoma.
Dongjun Lee, Mihyang Ha, +11 authors, Yun Hak Kim.
Oncol Lett, 2019 Dec 04; 18(6). PMID: 31788046    Free PMC article.
DGM-CM6: A New Model to Predict Distant Recurrence Risk in Operable Endocrine-Responsive Breast Cancer.
Lei Lei, Xiao-Jia Wang, +2 authors, Yunyun Zhou.
Front Oncol, 2020 Jun 13; 10. PMID: 32528885    Free PMC article.
Cascaded Wx: A Novel Prognosis-Related Feature Selection Framework in Human Lung Adenocarcinoma Transcriptomes.
Bonggun Shin, Sungsoo Park, +6 authors, Keunsoo Kang.
Front Genet, 2019 Aug 06; 10. PMID: 31379926    Free PMC article.
Strong impact of MammaPrint and BluePrint on treatment decisions in luminal early breast cancer: results of the WSG-PRIMe study.
R Wuerstlein, R Kates, +14 authors, WSG-PRIMe investigators in Germany, Austria, Switzerland.
Breast Cancer Res Treat, 2019 Feb 24; 175(2). PMID: 30796651    Free PMC article.