Journal Article
. 2010 Jul;12(4).
doi: 10.1186/bcr2604.

Mammostrat as a tool to stratify breast cancer patients at risk of recurrence during endocrine therapy

John M S Bartlett 1 Jeremy Thomas  Douglas T Ross  Robert S Seitz  Brian Z Ring  Rodney A Beck  Hans Christian Pedersen  Alison Munro  Ian H Kunkler  Fiona M Campbell  Wilma Jack  Gillian R Kerr  Laura Johnstone  David A Cameron  Udi Chetty  
Affiliations
  • PMID: 20615243
  •     17 References
  •     48 citations

Abstract

Introduction: Patients with early-stage breast cancer, treated with endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite endocrine therapy, additional adjuvant therapy, such as chemotherapy, may be indicated. The challenge is to prospectively identify such patients. The Mammostrat® test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions. We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up.

Methods: Tissue microarrays from a consecutive series (1981 to 1998) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review. Of 1,390 cases stained, 197 received no adjuvant hormonal or chemotherapy, 1,044 received tamoxifen only, and 149 received a combination of hormonal therapy and chemotherapy. Median age at diagnosis was 57, 71% were postmenopausal, 23.9% were node-positive and median tumor size was 1.5 cm. Samples were stained using triplicate 0.6 mm2 tissue microarray cores, and positivity for p53, HTF9C, CEACAM5, NDRG1 and SLC7A5 was assessed. Each case was assigned a Mammostrat risk score, and distant recurrence-free survival (DRFS), relapse-free survival (RFS) and overall survival (OS) were analyzed by marker positivity and risk score.

Results: Increased Mammostrat scores were significantly associated with reduced DRFS, RFS and OS in estrogen receptor (ER)-positive breast cancer (P < 0.00001). In multivariate analyses the risk score was independent of conventional risk factors for DRFS, RFS and OS (P < 0.05). In node-negative, tamoxifen-treated patients, 10-year recurrence rates were 7.6 ± 1.5% in the low-risk group versus 20.0 ± 4.4% in the high-risk group. Further, exploratory analyses revealed associations with outcome in both ER-negative and untreated patients.

Conclusions: This is the fifth independent study providing evidence that Mammostrat can act as an independent prognostic tool for ER-positive, tamoxifen-treated breast cancer. In addition, this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors. When viewed in the context of previous results, these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer.

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.
Pathological prognostic factors in breast cancer.
C W Elston, I O Ellis, S E Pinder.
Crit Rev Oncol Hematol, 1999 Oct 26; 31(3). PMID: 10532196
Review.
Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome.
Robert L Camp, Marisa Dolled-Filhart, Bonnie L King, David L Rimm.
Cancer Res, 2003 Apr 03; 63(7). PMID: 12670887
A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.
R Charles Coombes, Emma Hall, +24 authors, Intergroup Exemestane Study.
N Engl J Med, 2004 Mar 12; 350(11). PMID: 15014181
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.
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.
Automated quantitative analysis (AQUA) of in situ protein expression, antibody concentration, and prognosis.
Anthony McCabe, Marisa Dolled-Filhart, Robert L Camp, David L Rimm.
J Natl Cancer Inst, 2005 Dec 22; 97(24). PMID: 16368942
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.
Novel prognostic immunohistochemical biomarker panel for estrogen receptor-positive breast cancer.
Brian Z Ring, Robert S Seitz, +9 authors, Douglas T Ross.
J Clin Oncol, 2006 Jul 01; 24(19). PMID: 16809728
Summary of aromatase inhibitor clinical trials in postmenopausal women with early breast cancer.
Aman U Buzdar, R Charles Coombes, Paul E Goss, Eric P Winer.
Cancer, 2007 Dec 12; 112(3 Suppl). PMID: 18072256
Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes.
Christine Desmedt, Benjamin Haibe-Kains, +6 authors, Christos Sotiriou.
Clin Cancer Res, 2008 Aug 14; 14(16). PMID: 18698033
Highly Cited.
Chemosensitivity and stratification by a five monoclonal antibody immunohistochemistry test in the NSABP B14 and B20 trials.
Douglas T Ross, Chung-Yeul Kim, +7 authors, Norman Wolmark.
Clin Cancer Res, 2008 Oct 18; 14(20). PMID: 18927301    Free PMC article.
External quality assurance of HER2 FISH and ISH testing: three years of the UK national external quality assurance scheme.
John M S Bartlett, Merdol Ibrahim, +8 authors, Keith Miller.
Am J Clin Pathol, 2008 Dec 20; 131(1). PMID: 19095573
Up-front use of aromatase inhibitors as adjuvant therapy for breast cancer: the emperor has no clothes.
Bostjan Seruga, Ian F Tannock.
J Clin Oncol, 2009 Jan 14; 27(6). PMID: 19139426
Tamoxifen: the drug that came in from the cold.
L Hughes-Davies, C Caldas, G C Wishart.
Br J Cancer, 2009 Aug 13; 101(6). PMID: 19672259    Free PMC article.
Review.
Histological grading of invasive breast carcinoma--a simplification of existing methods in a large conservation series with long-term follow-up.
Jeremy St J Thomas, Gillian R Kerr, +7 authors, John M S Bartlett.
Histopathology, 2009 Oct 23; 55(6). PMID: 19845790
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.
Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53.
E K A Millar, P H Graham, +10 authors, R L Sutherland.
Br J Cancer, 2011 Jun 30; 105(2). PMID: 21712826    Free PMC article.
The Role of Proteomics in the Diagnosis and Treatment of Women's Cancers: Current Trends in Technology and Future Opportunities.
Eun-Kyoung Yim Breuer, Mandi M Murph.
Int J Proteomics, 2011 Sep 03; 2011. PMID: 21886869    Free PMC article.
Transfer RNA methytransferases and their corresponding modifications in budding yeast and humans: activities, predications, and potential roles in human health.
William L Towns, Thomas J Begley.
DNA Cell Biol, 2011 Dec 24; 31(4). PMID: 22191691    Free PMC article.
Review.
Hormonal therapy in breast cancer: a model disease for the personalization of cancer care.
Shannon Puhalla, Saveri Bhattacharya, Nancy E Davidson.
Mol Oncol, 2012 Mar 13; 6(2). PMID: 22406404    Free PMC article.
Review.
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.
Signatures of tumor-immune interactions as biomarkers for breast cancer prognosis.
Masoud H Manjili, Kayvan Najarian, Xiang-Yang Wang.
Future Oncol, 2012 Jul 07; 8(6). PMID: 22764768    Free PMC article.
Review.
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.
Breast Cancer Biomarkers: Utility in Clinical Practice.
Fanny Le Du, Naoto T Ueno, Ana M Gonzalez-Angulo.
Curr Breast Cancer Rep, 2014 Jan 15; 5(4). PMID: 24416469    Free PMC article.
Cost-effectiveness analysis of Mammostrat® compared with Oncotype DX® to inform the treatment of breast cancer.
Kimberly Mislick, Warren Schonfeld, Carolyn Bodnar, Kuo Bianchini Tong.
Clinicoecon Outcomes Res, 2014 Jan 29; 6. PMID: 24470765    Free PMC article.
Adaptive designs for clinical trials assessing biomarker-guided treatment strategies.
J Wason, A Marshall, +2 authors, N Stallard.
Br J Cancer, 2014 Mar 29; 110(8). PMID: 24667651    Free PMC article.
Garbage in, garbage out: a critical evaluation of strategies used for validation of immunohistochemical biomarkers.
Gillian O'Hurley, Evelina Sjöstedt, +5 authors, Cecilia Lindskog.
Mol Oncol, 2014 Apr 15; 8(4). PMID: 24725481    Free PMC article.
Review.
Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2- breast cancer patients: results from the GEICAM 9906 trial.
Miguel Martin, Jan C Brase, +15 authors, Alvaro Rodriguez-Lescure.
Breast Cancer Res, 2014 Apr 15; 16(2). PMID: 24725534    Free PMC article.
Predictive and prognostic value of the 21-gene recurrence score in hormone receptor-positive, node-positive breast cancer.
Adam M Brufsky.
Am J Clin Oncol, 2014 May 24; 37(4). PMID: 24853663    Free PMC article.
Systematic Review.
Twenty (forward looking) questions.
Lewis A Hassell, Elizabeth A Wagar.
J Pathol Inform, 2014 Sep 06; 5(1). PMID: 25191626    Free PMC article.
Time dependence of biomarkers: non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer.
J Stephen, G Murray, +13 authors, J M S Bartlett.
Br J Cancer, 2014 Oct 15; 111(12). PMID: 25314051    Free PMC article.
Clustering-Based Method for Developing a Genomic Copy Number Alteration Signature for Predicting the Metastatic Potential of Prostate Cancer.
Alexander Pearlman, Christopher Campbell, +8 authors, Harry Ostrer.
J Probab Stat, 2012 Jan 01; 2012(2012). PMID: 25419216    Free PMC article.
Association of survivin splice variants with prognosis and treatment of breast cancer.
Anastasia Pavlidou, Christos Kroupis, Kleanthi Dimas.
World J Clin Oncol, 2014 Dec 11; 5(5). PMID: 25493226    Free PMC article.
Review.
Immunohistochemistry and mass spectrometry for highly multiplexed cellular molecular imaging.
Richard M Levenson, Alexander D Borowsky, Michael Angelo.
Lab Invest, 2015 Mar 03; 95(4). PMID: 25730370    Free PMC article.
Review.
Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes.
Sandrine Caburet, Mikko Anttonen, +4 authors, Reiner A Veitia.
BMC Cancer, 2015 Apr 18; 15. PMID: 25884336    Free PMC article.
L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia.
Qian Wang, Jeff Holst.
Am J Cancer Res, 2015 Jun 24; 5(4). PMID: 26101697    Free PMC article.
Highly Cited. Review.
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.
Transfer RNA detection by small RNA deep sequencing and disease association with myelodysplastic syndromes.
Yan Guo, Amma Bosompem, +11 authors, Annette S Kim.
BMC Genomics, 2015 Sep 25; 16. PMID: 26400237    Free PMC article.
Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.
Ranad Shaheen, Ghada M H Abdel-Salam, +7 authors, Fowzan S Alkuraya.
Genome Biol, 2015 Sep 30; 16. PMID: 26416026    Free PMC article.
Identifying patients at high risk of breast cancer recurrence: strategies to improve patient outcomes.
Yehoda M Martei, Jennifer M Matro.
Breast Cancer (Dove Med Press), 2015 Oct 28; 7. PMID: 26504408    Free PMC article.
Review.
Mining the Breast Cancer Proteome for Predictors of Drug Sensitivity.
Leslie C Timpe, Dian Li, +4 authors, Alexandra Piryatinska.
J Proteomics Bioinform, 2015 Oct 31; 8(9). PMID: 26516301    Free PMC article.
Posttranscriptional methylation of transfer and ribosomal RNA in stress response pathways, cell differentiation, and cancer.
Martyna C Popis, Sandra Blanco, Michaela Frye.
Curr Opin Oncol, 2015 Nov 26; 28(1). PMID: 26599292    Free PMC article.
Review.
Breast cancer metastasis and the lymphatic system.
Munazzah Rahman, Sulma Mohammed.
Oncol Lett, 2015 Dec 02; 10(3). PMID: 26622656    Free PMC article.
A micro-RNA expression signature for human NAFLD progression.
Yan Guo, Yanhua Xiong, +3 authors, Charles Robb Flynn.
J Gastroenterol, 2016 Feb 15; 51(10). PMID: 26874844    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.
Personalized Prognostic Prediction Models for Breast Cancer Recurrence and Survival Incorporating Multidimensional Data.
Xifeng Wu, Yuanqing Ye, +11 authors, Gabriel N Hortobagyi.
J Natl Cancer Inst, 2017 Apr 05; 109(7). PMID: 28376179    Free PMC article.
Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models.
Safoora Yousefi, Fatemeh Amrollahi, +8 authors, Lee A D Cooper.
Sci Rep, 2017 Sep 17; 7(1). PMID: 28916782    Free PMC article.
Gene expression profiling to predict recurrence of advanced squamous cell carcinoma of the tongue: discovery and external validation.
Tomohiro Enokida, Satoshi Fujii, +7 authors, Makoto Tahara.
Oncotarget, 2017 Oct 06; 8(37). PMID: 28977904    Free PMC article.
Molecular Genomic Testing for Breast Cancer: Utility for Surgeons.
Oluwadamilola M Fayanju, Ko Un Park, Anthony Lucci.
Ann Surg Oncol, 2017 Nov 22; 25(2). PMID: 29159748    Free PMC article.
Review.
Prognostic & predictive factors for planning adjuvant chemotherapy of early-stage breast cancer.
Onur Esbah, Berna Oksuzoglu.
Indian J Med Res, 2018 Mar 08; 146(5). PMID: 29512598    Free PMC article.
Review.
Amino Acid Transporters and Glutamine Metabolism in Breast Cancer.
Yoon Jin Cha, Eun-Sol Kim, Ja Seung Koo.
Int J Mol Sci, 2018 Mar 23; 19(3). PMID: 29562706    Free PMC article.
Review.
The amino acid transporter SLC7A5 confers a poor prognosis in the highly proliferative breast cancer subtypes and is a key therapeutic target in luminal B tumours.
Rokaya El Ansari, Madeleine L Craze, +5 authors, Andrew R Green.
Breast Cancer Res, 2018 Mar 24; 20(1). PMID: 29566741    Free PMC article.
Highly Cited.
RNA-modifying proteins as anticancer drug targets.
P Ann Boriack-Sjodin, Scott Ribich, Robert A Copeland.
Nat Rev Drug Discov, 2018 May 19; 17(6). PMID: 29773918
Review.
The Regulation and Function of the L-Type Amino Acid Transporter 1 (LAT1) in Cancer.
Travis B Salisbury, Subha Arthur.
Int J Mol Sci, 2018 Aug 15; 19(8). PMID: 30103560    Free PMC article.
Review.
An Update on Breast Cancer Multigene Prognostic Tests-Emergent Clinical Biomarkers.
André Filipe Vieira, Fernando Schmitt.
Front Med (Lausanne), 2018 Sep 21; 5. PMID: 30234119    Free PMC article.
Review.
Microarray and RNA in situ hybridization assay for recurrence risk markers of breast carcinoma and ductal carcinoma in situ: Evidence supporting the use of diverse pathways panels.
Mark Francis Evans, Pamela Mary Vacek, +3 authors, Donald Lee Weaver.
J Cell Biochem, 2019 Oct 09; 121(2). PMID: 31595577    Free PMC article.
Evaluation of the predictive ability of ultrasound-based assessment of breast cancer using BI-RADS natural language reporting against commercial transcriptome-based tests.
Neema Jamshidii, Jason Chang, +3 authors, Michael D Kuo.
PLoS One, 2020 Jan 11; 15(1). PMID: 31923222    Free PMC article.
Global analysis of tRNA and translation factor expression reveals a dynamic landscape of translational regulation in human cancers.
Zhao Zhang, Youqiong Ye, +9 authors, Leng Han.
Commun Biol, 2018 Dec 28; 1. PMID: 30588513    Free PMC article.
Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1-NDRG1 axis in both PR-positive and -negative breast cancer cells.
Mukul Godbole, Trupti Togar, +17 authors, Amit Dutt.
J Biol Chem, 2018 Oct 20; 293(50). PMID: 30337371    Free PMC article.
HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer.
Ellen C de Heer, Mathilde Jalving, Adrian L Harris.
J Clin Invest, 2020 Sep 02; 130(10). PMID: 32870818    Free PMC article.
Review.
Review of the Correlation of LAT1 With Diseases: Mechanism and Treatment.
Jingshun Zhang, Ying Xu, +4 authors, Lianwen Zheng.
Front Chem, 2020 Nov 17; 8. PMID: 33195053    Free PMC article.
Review.
Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer.
Harmen Hawer, Alexander Hammermeister, +3 authors, Roland Klassen.
Genes (Basel), 2019 Jan 02; 10(1). PMID: 30597914    Free PMC article.
Review.
Advanced Approaches to Breast Cancer Classification and Diagnosis.
M Zubair, S Wang, N Ali.
Front Pharmacol, 2021 Mar 16; 11. PMID: 33716731    Free PMC article.
Review.
Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast.
Sunil S Badve, Sanghee Cho, +10 authors, Fiona Ginty.
Br J Cancer, 2021 Jan 09; 124(6). PMID: 33414541    Free PMC article.