Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Ophthalmology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
ASH 2024 Annual Meeting 2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.

Published: Thursday 12th December 2024
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment

Open Access 03-02-2025 | Cytostatic Therapy | Review

Gene expression profiling tests to guide adjuvant chemotherapy decisions in lymph node-positive early breast cancer: a systematic review

Authors: Katy Cooper, Gamze Nalbant, Munira Essat, Sue Harnan, Ruth Wong, Jean Hamilton, Uzma S. Asghar, Nicolò M. L. Battisti, Lynda Wyld, Paul Tappenden

Published in: Breast Cancer Research and Treatment

Login to get access

Abstract

Purpose

To systematically review the effectiveness of gene expression profiling tests to inform adjuvant chemotherapy decisions in people with hormone receptor-positive (HR+), lymph node-positive (LN+) breast cancer.

Methods

This systematic review assessed the effectiveness of Oncotype DX, Prosigna, EndoPredict and MammaPrint for guiding adjuvant chemotherapy decisions in HR+ early breast cancer with 1–3 positive nodes, in terms of prognostic ability, prediction of chemotherapy benefit, impact on chemotherapy decisions, quality of life and anxiety. Searches covered MEDLINE, EMBASE and Cochrane databases in April 2023.

Results

Fifty-five articles were included. All four tests were prognostic for distant recurrence in LN+ patients. The RxPONDER trial reported no chemotherapy benefit in post-menopausal LN+ patients with low Oncotype DX (RS 0–25), whilst pre-menopausal patients had statistically significant chemotherapy benefit. An RCT reanalysis of Oncotype DX (SWOG-8814) suggested greater chemotherapy benefit with higher RS in post-menopausal LN+ patients. The MINDACT trial reported that LN+ patients with high clinical risk and low MammaPrint risk had a non-statistically significant chemotherapy benefit, but was not designed assess differential chemotherapy benefit per risk group. Decisions to undergo chemotherapy reduced by 12–75% following Oncotype DX testing in LN+ patients in the UK and Europe. No studies in LN+ populations were identified for prediction of chemotherapy benefit by Prosigna or EndoPredict; or for chemotherapy decisions for Prosigna, EndoPredict or MammaPrint; or for anxiety or quality of life impact for any test.

Conclusions

All four tests have prognostic ability in LN+ patients. Evidence on predictive benefit is weaker, with equivocal evidence that Oncotype DX may predict chemotherapy benefit in LN+ post-menopausal patients. Use of Oncotype DX leads to fewer patients being recommended chemotherapy.
Appendix
Available only for authorised users
Literature
1.
National Institute for Health and Care Excellence (2018) NICE Guideline 101. Early and locally advanced breast cancer: diagnosis and management. NICE, London, pp 1–71
2.
Lee AH, Ellis IO (2008) The Nottingham prognostic index for invasive carcinoma of the breast. Pathol Oncol Res 14:113–115PubMedCrossRef
3.
Hajage D, de Rycke Y, Bollet M, Savignoni A, Caly M, Pierga JY et al (2011) External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement. PLoS ONE 6:e27446PubMedPubMedCentralCrossRef
4.
Candido Dos Reis FJ, Wishart GC, Dicks EM, Greenberg D, Rashbass J, Schmidt MK et al (2017) An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation. Breast Cancer Res 19(1):58PubMedPubMedCentralCrossRef
5.
University of Sheffield (2024) Age gap decision tool. University of Sheffield, Sheffield
6.
Harnan S, Tappenden P, Cooper K, Stevens J, Bessey A, Rafia R et al (2019) Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis. Health Technol Assess 23:1–328PubMedPubMedCentralCrossRef
7.
National Institute for Health and Care Excellence (2018) Diagnostics guidance 34. Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer. NICE, London, pp 1–62
8.
Andre F, Ismaila N, Allison KH, Barlow WE, Collyar DE, Damodaran S et al (2022) Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol 40:1816–1837PubMedCrossRef
9.
National Institute for Health and Care Excellence (2024) Diagnostics guidance 58. Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer. NICE, London
10.
Piccart M, van’t Veer LJ, Poncet C, Lopes Cardozo JMN, Delaloge S, Pierga J-Y et al (2021) 70-Gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol 22:476–488PubMedCrossRef
11.
12.
Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman J-AW et al (2007) Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 25:2127–2132PubMedCrossRef
13.
Tolaney SM, Garrett-Mayer E, White J, Blinder VS, Foster JC, Amiri-Kordestani L et al (2021) Updated standardized definitions for efficacy end points (STEEP) in adjuvant breast cancer clinical trials: STEEP version 2.0. J Clin Oncol 39:2720–2731PubMedPubMedCentralCrossRef
14.
Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. Br Med J 366:l4898CrossRef
15.
Wolff RF, Moons KGM, Riley RD, Whiting PF, Westwood M, Collins GS et al (2019) PROBAST: a tool to assess the risk of bias and applicability of prediction model studies. Ann Intern Med 170:51–58PubMedCrossRef
16.
Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF et al (2021) 21-Gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med 385:2336–2347PubMedPubMedCentralCrossRef
17.
Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT et al (2010) 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 11:55–65PubMedCrossRef
18.
Kalinsky KM, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF et al (2022) Updated results from a phase 3 randomized clinical trial in participants (pts) with 1–3 positive lymph nodes (LN), hormone receptor-positive (HR+) and HER2-negative (HER2−) breast cancer (BC) with recurrence score (RS) < 25 randomized to endocrine therapy (ET) +/− chemotherapy (CT): SWOG S1007 (RxPONDER). Cancer Res. https://​doi.​org/​10.​1158/​1538-7445.​SABCS21-GS2-07CrossRef
19.
Mook S, Schmidt MK, Viale G, Pruneri G, Eekhout I, Floore A et al (2009) The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat 116:295–302PubMedCrossRef
20.
Sestak I, Buus R, Cuzick J, Dubsky P, Kronenwett R, Denkert C et al (2018) Comparison of the performance of 6 prognostic signatures for estrogen receptor-positive breast cancer: a secondary analysis of a randomized clinical trial. JAMA Oncol 4:545–553PubMedPubMedCentralCrossRef
21.
Mamounas EP, Tang G, Paik S, Baehner FL, Liu Q, Jeong J-H et al (2018) 21-Gene recurrence score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology. Breast Cancer Res Treat 168:69–77PubMedCrossRef
22.
Drukker CA, van Tinteren H, Schmidt MK, Rutgers EJ, Bernards R, van de Vijver MJ et al (2014) Long-term impact of the 70-gene signature on breast cancer outcome. Breast Cancer Res Treat 143:587–592PubMedPubMedCentralCrossRef
23.
Vliek SB, Retel V, Drukker C, Bueno-De-Mesquita JM, Rutgers E, Van Tinteren H et al (2017) The 70-gene signature in node positive breast cancer: 10-year follow-up of the observational RASTER study. Ann Oncol 28:v60CrossRef
24.
Gnant M, Filipits M, Greil R, Stoeger H, Rudas M, Bago-Horvath Z et al (2014) 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 25:339–345PubMedCrossRef
25.
Filipits M, Nielsen TO, Rudas M, Greil R, Stöger H, Jakesz R et al (2014) 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 20:1298–1305PubMedCrossRef
26.
Laenkholm A-V, Jensen M-B, Eriksen JO, Rasmussen BB, Knoop AS, Buckingham W et al (2018) PAM50 risk of recurrence score predicts 10-year distant recurrence in a comprehensive Danish cohort of postmenopausal women allocated to 5 years of endocrine therapy for hormone receptor-positive early breast cancer. J Clin Oncol 36:735–740PubMedCrossRef
27.
Martin M, Brase JC, Ruiz A, Prat A, Kronenwett R, Calvo L et al (2016) Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study. Breast Cancer Res Treat 156:81–89PubMedPubMedCentralCrossRef
28.
Martin M, Brase JC, Calvo L, Krappmann K, Ruiz-Borrego M, Fisch K et al (2014) 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 16:R38PubMedPubMedCentralCrossRef
29.
Filipits M, Dubsky P, Rudas M, Greil R, Balic M, Bago-Horvath Z et al (2019) Prediction of distant recurrence using EndoPredict among women with ER+, HER2− node-positive and node-negative breast cancer treated with endocrine therapy only. Clin Cancer Res 25:3865–3872PubMedCrossRef
30.
Constantinidou A, Marcou Y, Toss MS, Simmons T, Bernhisel R, Hughes E et al (2022) Clinical validation of EndoPredict in pre-menopausal women with ER-positive, HER2-negative primary breast cancer. Clin Cancer Res 28:4435–4443PubMedPubMedCentralCrossRef
31.
32.
Penault-Llorca F, Filleron T, Asselain B, Baehner FL, Fumoleau P, Lacroix-Triki M et al (2018) The 21-gene Recurrence Score R assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial). BMC Cancer 18:526PubMedPubMedCentralCrossRef
33.
Jackisch C, Pronin D, Dimpfl T, Buttner R, Kunz G, Langwieder C et al (2022) MammaPrint 10-year follow up results from a German breast cancer cohort study. Ann Oncol 33:S612CrossRef
34.
Pu M, Messer K, Davies SR, Vickery TL, Pittman E, Parker BA et al (2020) Research-based PAM50 signature and long-term breast cancer survival. Breast Cancer Res Treat 179:197–206PubMedCrossRef
35.
Lundgren C, Bendahl P-O, Church SE, Ekholm M, Ferno M, Forsare C et al (2022) PAM50 subtyping and ROR score add long-term prognostic information in premenopausal breast cancer patients. NPJ Breast Cancer 8:61PubMedPubMedCentralCrossRef
36.
Sestak I, Filipits M, Buus R, Rudas M, Balic M, Knauer M et al (2020) Prognostic value of EndoPredict in women with hormone receptor-positive, HER2-negative invasive lobular breast cancer. Clin Cancer Res 26:4682–4687PubMedCrossRef
37.
Sestak I, Dowsett M, Cuzick J (2017) NICE Request—TransATAC data analysis [unpublished communication]
38.
39.
Lopes Cardozo JMN, Drukker CA, Rutgers EJT, Schmidt MK, Glas AM, Witteveen A et al (2022) Outcome of patients with an ultralow-risk 70-gene signature in the MINDACT trial. J Clin Oncol 40:1335–1345PubMedCrossRef
40.
Ibraheem A, Olopade OI, Huo D (2020) Propensity score analysis of the prognostic value of genomic assays for breast cancer in diverse populations using the National Cancer Data Base. Cancer 126:4013–4022PubMedCrossRef
41.
Ibraheem AF, Press DJ, Olopade OI, Huo D (2019) Community clinical practice patterns and mortality in patients with intermediate Oncotype DX recurrence scores: who benefits from chemotherapy? Cancer 125:213–222PubMedCrossRef
42.
Nash AL, Ren Y, Plichta JK, Rosenberger LH, van den Bruele AMB, DiNome ML et al (2023) Survival benefit of chemotherapy according to 21-gene recurrence score in young women with breast cancer. Ann Surg Oncol 30:2130–2139PubMedCrossRef
43.
Weiser R, Polychronopoulou E, Hatch SS, Haque W, Ghani HA, He J et al (2022) Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: a National Cancer Database analysis. Cancer 128:1738–1747PubMedCrossRef
44.
Weiser R, Haque W, Polychronopoulou E, Hatch SS, Kuo Y-F, Gradishar WJ et al (2021) The 21-gene recurrence score in node-positive, hormone receptor-positive, HER2-negative breast cancer: a cautionary tale from an NCDB analysis. Breast Cancer Res Treat 185:667–676PubMedCrossRef
45.
Petkov VI, Miller DP, Howlader N, Gliner N, Howe W, Schussler N et al (2016) Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study. NPJ Breast Cancer 2:16017PubMedPubMedCentralCrossRef
46.
Roberts MC, Miller DP, Shak S, Petkov VI (2017) Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database. Breast Cancer Res Treat 163:303–310PubMedCrossRef
47.
Massarweh SA, Sledge GW, Miller DP, McCullough D, Petkov VI, Shak S (2018) Molecular characterization and mortality from breast cancer in men. J Clin Oncol 36:1396–1404PubMedPubMedCentralCrossRef
48.
Stemmer SM, Steiner M, Rizel S, Geffen DB, Nisenbaum B, Peretz T et al (2017) Clinical outcomes in ER+ HER2− node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry. NPJ Breast Cancer 3:32PubMedPubMedCentralCrossRef
49.
Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC et al (2020) Prognostic impact of the 21-gene recurrence score assay among young women with node-negative and node-positive ER-positive/HER2-negative breast cancer. J Clin Oncol 38:725–733PubMedCrossRef
50.
Nitz U, Gluz O, Christgen M, Kates RE, Clemens M, Malter W et al (2017) Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial. Breast Cancer Res Treat 165:573–583PubMedPubMedCentralCrossRef
51.
Braun M, Kriegmair A, Szeterlak N, Andrulat A, Schrodi S, Kriner M et al (2022) Validation of the 21-gene recurrence score assay in patients with hormone receptor-positive, HER2-negative breast cancer and 0 to 3 positive lymph nodes: risk pattern and outcomes on a community level. Breast Care 17:288–295PubMedCrossRef
52.
Rotem O, Peretz I, Leviov M, Kuchuk I, Itay A, Tokar M et al (2022) Clinical outcomes in ER+ breast cancer patients with recurrence score 26–30-guided therapy: real-world data. Ann Oncol 33:S607–S608CrossRef
53.
54.
Abel MK, Shui AM, Chien AJ, Rugo HS, Melisko M, Baehner F et al (2022) The 21-gene recurrence score in clinically high-risk lobular and ductal breast cancer: a National Cancer Database study. Ann Surg Oncol 29:7739–7747PubMedPubMedCentralCrossRef
55.
Cao L, Towe CW, Luo X, Stabellini N, Amin AL, Montero AJ (2022) Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in patients with ER+/HER2− breast cancer with 1–3 positive nodes and Oncotype DX recurrence score 20 to 25: a National Cancer Database analysis. J Clin Oncol 40:540. https://​doi.​org/​10.​1200/​JCO.​2022.​40.​16_​suppl.​540
56.
57.
58.
Battisti NML, Gutteridge E, Mylvaganam S, Parton M, Ring A, McGrath SE (2019) The Oncotype DX Breast test to guide management of node-positive oestrogen receptor-positive HER2-negative breast cancer patients: the United Kingdom experience. Breast 44:S17CrossRef
59.
60.
Loncaster J, Armstrong A, Howell S, Wilson G, Welch R, Chittalia A et al (2017) Impact of Oncotype DX breast Recurrence Score testing on adjuvant chemotherapy use in early breast cancer: real world experience in Greater Manchester, UK. Eur J Surg Oncol 43:931–937PubMedCrossRef
61.
Malam Y, Rabie M, Geropantas K, Alexander S, Pain S, Youssef M (2022) The impact of Oncotype DX testing on adjuvant chemotherapy decision making in 1–3 node positive breast cancer. Cancer Rep 5:e1546CrossRef
62.
Nanda A, Yarwood A, Dillon M, Roy PG (2021) P120. Combined experience of utility of genomic profiling in lymph node-positive breast cancer: reduced prescription of chemotherapy and follow-up. Eur J Surg Oncol 47:e327CrossRef
63.
Cognetti F, Masetti R, Fabi A, Bianchi G, Santini D, Rognone A et al (2021) PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy. NPJ Breast Cancer 7:47PubMedPubMedCentralCrossRef
64.
Dieci MV, Guarneri V, Giarratano T, Mion M, Tortora G, De Rossi C et al (2018) First prospective multicenter Italian study on the impact of the 21-gene recurrence score in adjuvant clinical decisions for patients with ER positive/HER2 negative breast cancer. Oncologist 23:297–305PubMedCrossRef
65.
Dieci MV, Guarneri V, Zustovich F, Mion M, Morandi P, Bria E et al (2019) Impact of 21-gene breast cancer assay on treatment decision for patients with T1–T3, N0–N1, estrogen receptor-positive/human epidermal growth receptor 2-negative breast cancer: final results of the prospective multicenter ROXANE study. Oncologist 24:1424–1431PubMedPubMedCentralCrossRef
66.
Fernandez-Perez I, Antolin Novoa S, De Paz AL, Vazquez Tunas L, Perez Lopez ME, Varela Ferreiro S et al (2021) 60P real-life use of Oncotype DX Breast Recurrence Score test for the management of patients with node-negative and node-positive breast cancer in the autonomous community of Galicia (Spain). Ann Oncol 32:S46CrossRef
67.
Llombart-Cussac A, Anton-Torres A, Rojas B, Andres R, Martinez N, Rodriguez CA et al (2023) Impact of the 21-gene assay in patients with high-clinical risk ER-positive and HER2-negative early breast cancer: results of the KARMA DX study. Cancers 15(5):1529PubMedPubMedCentralCrossRef
68.
Zambelli A, Simoncini E, Giordano M, La Verde N, Farina G, Torri V et al (2020) Prospective observational study on the impact of the 21-gene assay on treatment decisions and resources optimization in breast cancer patients in Lombardy: the BONDX study. Breast 52:1–7PubMedPubMedCentralCrossRef
69.
Eiermann W, Rezai M, Kümmel S, Kühn T, Warm M, Friedrichs K et al (2013) The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use. Ann Oncol 24:618–624PubMedCrossRef
70.
Holt S, Verrill M, Pettit L, Rigg A, Hickish T, Archer C et al (2024) A UK prospective multicentre decision impact, decision conflict and economic evaluation of the 21-gene assay in women with node+ve, hormone receptor+ve, HER2-ve breast cancer. Br J Cancer 130:1149–1156PubMedPubMedCentralCrossRef
71.
Zhao A, Larbi M, Miller K, O’Neill S, Jayasekera J (2022) A scoping review of interactive and personalized web-based clinical tools to support treatment decision making in breast cancer. Breast 61:43–57PubMedCrossRef
72.
Battisti NML, De Glas N, Soto-Perez-de-Celis E, Liposits G, Bringuier M, Walko C et al (2022) Chemotherapy and gene expression profiling in older early luminal breast cancer patients: an International Society of Geriatric Oncology systematic review. Eur J Cancer 172:158–170PubMedPubMedCentralCrossRef
Metadata
Title
Gene expression profiling tests to guide adjuvant chemotherapy decisions in lymph node-positive early breast cancer: a systematic review
Authors
Katy Cooper
Gamze Nalbant
Munira Essat
Sue Harnan
Ruth Wong
Jean Hamilton
Uzma S. Asghar
Nicolò M. L. Battisti
Lynda Wyld
Paul Tappenden
Publication date
03-02-2025
Publisher
Springer US
Published in
Breast Cancer Research and Treatment
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-024-07596-0

ASH 2024 Annual Meeting Coverage

inMIND supports tafasitamab addition in follicular lymphoma

Combining tafasitamab with lenalidomide and rituximab significantly improves progression-free survival for patients with relapsed or refractory follicular lymphoma.

Featuring the official presentation video

Read more

Transplantation can be omitted for certain MCL patients

Add-on blinatumomab improves DFS in children with ALL

Promising response to loncastuximab tesirine in lymphoma

» View more highlights on the ASH 2024 hub page

SPONSORED

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

In this webinar, Professor Martin Dreyling and an esteemed international panel of CAR T-cell therapy experts discuss the latest data on the safety, efficacy, and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL.

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by:
  • Novartis Pharma AG
Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare
Watch now
Image Credits