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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Current Treatment Options in Oncology
Published in: Current Treatment Options in Oncology 5/2015

01-05-2015 | Breast Cancer (P Neven, Section Editor)

Indications for Prognostic Gene Expression Profiling in Early Breast Cancer

Authors: Erin F. Cobain, MD, Daniel F. Hayes, MD

Published in: Current Treatment Options in Oncology | Issue 5/2015

Login to get access

Opinion statement

Breast cancer is a heterogeneous disease. While breast cancer mortality has dropped substantially over the past three decades due to early detection and adjuvant systemic therapy (AST), the risk of recurrence is highly dependent upon numerous factors including tumor size, involvement of regional lymph nodes, histologic grade, expression of hormone receptors (estrogen and progesterone), and human epidermal growth factor receptor 2 (HER2) amplification. We use these factors to determine which early breast cancer (EBC) patients should be treated with AST, including endocrine therapy (ET), chemotherapy, and HER2-directed treatments. While these factors aid in this determination, it remains challenging to identify those patients unlikely to benefit from adjuvant chemotherapy, resulting in over-treatment of patients. Given this dilemma, there has been great interest in the development of prognostic and predictive gene expression profiles. The most extensively studied profile, the 21-gene recurrence score (Oncotype Dx®), estimates 10-year risk of breast cancer recurrence in patients with estrogen receptor (ER)-positive, HER2-negative, node-negative EBC and is likely predictive of chemotherapy benefit. This assay has established analytic validity, clinical validity, and clinical utility for this patient group and, therefore, is indicated in this patient population to help inform decisions regarding administration of adjuvant chemotherapy. Several other assays may have utility in this clinical context or perhaps to identify patients who do not require extended adjuvant ET. These assays include the following: PAM 50 Risk of Recurrence (ROR) Score (Prosigna™), Breast Cancer Index, and EndoPredict®.
Literature
1.
Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784–92.PubMedCrossRef
2.
Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol. 2014;32:2255–69.PubMedCrossRef
3.
Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012;4, CD006243.PubMed
4.
Early Breast Cancer Trialists’ Collaborative G, Peto R, Davies C, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432–44.CrossRef
5.
6.
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.PubMedCrossRef
7.
Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378:771–84.PubMedCrossRef
8.
Early Breast Cancer Trialists’ Collaborative G. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.CrossRef
9.
Bartlett JM, Brookes CL, Robson T, et al. Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the Tamoxifen and Exemestane Adjuvant Multinational trial. J Clin Oncol. 2011;29:1531–8.PubMedCentralPubMedCrossRef
10.
Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26:5697–704.PubMedCrossRef
11.
Gusterson BA, Gelber RD, Goldhirsch A, et al. Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group. J Clin Oncol. 1992;10:1049–56.PubMed
12.
Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24:2206–23.PubMedCentralPubMedCrossRef
13.
Fisher B, Jeong JH, Bryant J, et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004;364:858–68.PubMedCrossRef
14.
Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006;295:1658–67.PubMedCentralPubMedCrossRef
15.
Lippman ME, Allegra JC, Thompson EB, et al. The relation between estrogen receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer. N Engl J Med. 1978;298:1223–8.PubMedCrossRef
16.
Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRef
17.
Hayes DF. Targeting adjuvant chemotherapy: a good idea that needs to be proven! J Clin Oncol. 2012;30:1264–7.PubMedCrossRef
18.
Teutsch SM, Bradley LA, Palomaki GE, et al. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group. Genet Med. 2009;11:3–14.PubMedCentralPubMedCrossRef
19.
Institute of Medicine: Evolution of translational omics: lessons learned and the path forward. Washington, D.C., The National Academies Press, 2012.
20.
Hayes DF, Bast RC, Desch CE, et al. Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst. 1996;88:1456–66.PubMedCrossRef
21.
22.
Pepe MS, Feng Z, Janes H, et al. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J Natl Cancer Inst. 2008;100:1432–8.PubMedCentralPubMedCrossRef
23.
Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef
24.
Cronin M, Sangli C, Liu ML, et al. Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer. Clin Chem. 2007;53:1084–91.PubMedCrossRef
25.
Dowsett M, Cuzick J, Wale C, et al. 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. J Clin Oncol. 2010;28:1829–34.PubMedCrossRef
26.
Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010;28:1677–83.PubMedCentralPubMedCrossRef
27.••
Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–34. In this prospective-retrospective analysis of patients enrolled in NSABP-B20, patients with high 21-gene RS had a higher proportional reduction in risk of distant recurrence when administered adjuvant chemotherapy than those patients with low RS. This study supports the hypothesis that benefit from chemotherapy may be impacted by tumor biology.PubMedCrossRef
28.
Albain KS, Barlow WE, Shak S, et al. 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. Lancet Oncol. 2010;11:55–65.PubMedCentralPubMedCrossRef
29.
Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.PubMedCrossRef
30.
31.
van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.CrossRef
32.
Ach RA, Floore A, Curry B, et al. Robust interlaboratory reproducibility of a gene expression signature measurement consistent with the needs of a new generation of diagnostic tools. BMC Genomics. 2007;8:148.PubMedCentralPubMedCrossRef
33.
Glas AM, Floore A, Delahaye LJ, et al. Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics. 2006;7:278.PubMedCentralPubMedCrossRef
34.
van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef
35.
Buyse M, Loi S, van’t Veer L, et al. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006;98:1183–92.PubMedCrossRef
36.
37.
Nielsen T, Wallden B, Schaper C, et al. Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer. 2014;14:177.PubMedCentralPubMedCrossRef
38.
Chia SK, Bramwell VH, Tu D, et al. A 50-gene intrinsic subtype classifier for prognosis and prediction of benefit from adjuvant tamoxifen. Clin Cancer Res. 2012;18:4465–72.PubMedCentralPubMedCrossRef
39.••
Dowsett M, Sestak I, Lopez-Knowles E, et al. Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol. 2013;31:2783–90. Clinical validity and prognostic utility of the ROR score were demonstrated in this study, where ROR score was found to have a continuous relationship with risk of distant recurrence at 10 years.PubMedCrossRef
40.
Gnant M, Filipits M, Greil R, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol. 2014;25:339–45.PubMedCrossRef
41.•
Filipits M, Nielsen TO, Rudas M, et al. The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res. 2014;20:1298–305. Prospective-retrospective analysis of patients with ER-positive EBC treated with adjuvant tamoxifen or adjuvant tamoxifen followed by anastrazole (ABCSG-8 trial). ROR score risk group was predictive of late (5–15 years) distant recurrence in these patients.PubMedCrossRef
42.
Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–9.PubMedCrossRef
43.
Desmedt C, Piette F, Loi S, et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13:3207–14.PubMedCrossRef
44.
Foekens JA, Atkins D, Zhang Y, et al. Multicenter validation of a gene expression-based prognostic signature in lymph node-negative primary breast cancer. J Clin Oncol. 2006;24:1665–71.PubMedCrossRef
45.
Sotiriou C, Wirapati P, Loi S, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98:262–72.PubMedCrossRef
46.
Loi S, Haibe-Kains B, Desmedt C, et al. Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol. 2007;25:1239–46.PubMedCrossRef
47.
Bertucci F, Finetti P, Roche H, et al. Comparison of the prognostic value of genomic grade index, Ki67 expression and mitotic activity index in early node-positive breast cancer patients. Ann Oncol. 2013;24:625–32.PubMedCrossRef
48.
Liedtke C, Hatzis C, Symmans WF, et al. Genomic grade index is associated with response to chemotherapy in patients with breast cancer. J Clin Oncol. 2009;27:3185–91.PubMedCentralPubMedCrossRef
49.
Ma XJ, Wang Z, Ryan PD, et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell. 2004;5:607–16.PubMedCrossRef
50.
Jansen MP, Sieuwerts AM, Look MP, et al. HOXB13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study. J Clin Oncol. 2007;25:662–8.PubMedCrossRef
51.•
Sgroi DC, Sestak I, Cuzick J, et al. Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol. 2013;14:1067–76. Prospective-retrospective analysis of patients with ER-positive, node negative EBC enrolled in the ATAC trial, comparing BCI to 21-gene RS and IHC4. BCI was predictive of late recurrence in this study, whereas 21-gene RS and IHC4 were not, potentially identifying a population of patients that may not benefit from extended adjuvant ET.PubMedCentralPubMedCrossRef
52.
Zhang Y, Schnabel CA, Schroeder BE, et al. Breast cancer index identifies early-stage estrogen receptor-positive breast cancer patients at risk for early- and late-distant recurrence. Clin Cancer Res. 2013;19:4196–205.PubMedCrossRef
53.
Jerevall PL, Ma XJ, Li H, et al. Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. Br J Cancer. 2011;104:1762–9.PubMedCentralPubMedCrossRef
54.
Denkert C, Kronenwett R, Schlake W, et al. Decentral gene expression analysis for ER+/Her2− breast cancer: results of a proficiency testing program for the EndoPredict assay. Virchows Arch. 2012;460:251–9.PubMedCentralPubMedCrossRef
55.
Muller BM, Brase JC, Haufe F, et al. Comparison of the RNA-based EndoPredict multigene test between core biopsies and corresponding surgical breast cancer sections. J Clin Pathol. 2012;65:660–2.PubMedCentralPubMedCrossRef
56.
Filipits M, Rudas M, Jakesz R, et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 2011;17:6012–20.PubMedCrossRef
57.•
Dubsky P, Brase JC, Jakesz R, et al. The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. Br J Cancer. 2013;109:2959–64. In this study, EPclin scores identified a subgroup of patients with an excellent long-term prognosis with 5 years of adjuvant ET, potentially identifying a population of patients that may not benefit from extended adjuvant ET.PubMedCentralPubMedCrossRef
58.•
Martin M, Brase JC, Calvo L, et al. Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2− breast cancer patients: results from the GEICAM 9906 trial. Breast Cancer Res. 2014;16:R38. Prospective-retrospective study including over 1,200 samples from patients with ER-positive, HER2-negative EBC treated with adjuvant chemotherapy, demonstrating that EP scores were highly predictive of metastasis-free survival in both high and low risk groups.PubMedCentralPubMedCrossRef
59.
Varga Z, Sinn P, Fritzsche F, et al. Comparison of EndoPredict and Oncotype DX test results in hormone receptor positive invasive breast cancer. PLoS One. 2013;8, e58483.PubMedCentralPubMedCrossRef
Metadata
Title
Indications for Prognostic Gene Expression Profiling in Early Breast Cancer
Authors
Erin F. Cobain, MD
Daniel F. Hayes, MD
Publication date
01-05-2015
Publisher
Springer US
Published in
Current Treatment Options in Oncology / Issue 5/2015
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-015-0340-x

Other articles of this Issue 5/2015

Current Treatment Options in Oncology 5/2015 Go to the issue

Sarcoma (SH Okuno, Section Editor)

Soft Tissue Sarcoma and Radiation Therapy Advances, Impact on Toxicity

Upper Gastrointestinal Cancers (L Rajdev, Section Editor)

Immunotherapy in Upper GI Malignancies

Gynecologic Cancers (RJ Morgan, Section Editor)

Dose-Dense Approaches to Ovarian Cancer Treatment

Sarcoma (SH Okuno, Section Editor)

Role of Genetic and Molecular Profiling in Sarcomas

Breast Cancer (P Neven, Section Editor)

Obesity and Breast Cancer: Not Only a Risk Factor of the Disease
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