Journal Article
. 2015 May; 26(8):1685-91.
doi: 10.1093/annonc/mdv215.

Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype

M Gnant 1 I Sestak 2 M Filipits 3 M Dowsett 4 M Balic 5 E Lopez-Knowles 6 R Greil 7 P Dubsky 8 H Stoeger 5 M Rudas 9 R Jakesz 8 S Ferree 10 J W Cowens 10 T Nielsen 11 C Schaper 12 C Fesl 13 J Cuzick 2 
Affiliations
  • PMID: 25935792
  •     31 citations

Abstract

Background: In the adjuvant treatment of hormone receptor-positive (HR+) breast cancer, variables like tumour size, grade and nodal status have great impact on therapy decisions. As most node-positive patients with HR+ breast cancer currently receive adjuvant chemotherapy improved methods for characterization of individuals' metastasis risk are needed to reduce overtreatment.

Patients And Methods: Tissue specimens from node-positive patients of the ABCSG-8 and ATAC trials who received adjuvant tamoxifen and/or anastrozole were included in this study. Analysing RNA from paraffin blocks using the PAM50 test, the primary objective was to evaluate the prognostic information of the risk of recurrence (ROR) score added to combined clinical standard variables in patients with one positive node (1N+) and in patients with two or three positive nodes (2-3N+), using log-likelihood ratio tests.

Results: At a median follow-up of 9.6 years, distant metastases occurred in 97 (18%) of 543 node-positive patients. In a multivariate analysis, the PAM50-derived ROR score provided reliable prognostic information in addition to and beyond established clinical factors for 1N+ (P < 0.0001) and 2-3N+ patients (P = 0.0002). Ten-year distant recurrence risk was significantly increased in the high-risk compared with the low-risk group derived from ROR score for 1N+ [25.5%, 95% confidence interval (CI) 17.5% to 36.1%versus 6.6%, 95% CI 3.3% to 12.8%] and compared with the combined low/intermediate risk group for 2-3N+ patients (33.7%, 95% CI 25.5% to 43.8% versus 12.5%, 95% CI 6.6% to 22.8%). Additionally, the luminal A intrinsic subtype (IS) exhibited significantly lower risk of distant recurrence compared with the luminal B subtype in 1N+ and 2-3N+ patients.

Conclusion: PAM50 ROR score and IS can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared. The PAM50 test is a valuable tool in determining treatment of node-positive early-stage breast cancer patients.

Keywords: early-stage breast cancer (EBC); intrinsic subtype (IS); multigenomic testing; node-positive patients; prognostic subtypes; risk of recurrence (ROR).

Genomic profiling in luminal breast cancer.
Oleg Gluz, Daniel Hofmann, +3 authors, Nadia Harbeck.
Breast Care (Basel), 2014 Feb 20; 8(6). PMID: 24550749    Free PMC article.
Review.
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.
Torsten Nielsen, Brett Wallden, +7 authors, James Storhoff.
BMC Cancer, 2014 Mar 15; 14. PMID: 24625003    Free PMC article.
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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.
Diagnostic tests based on gene expression profile in breast cancer: from background to clinical use.
Laura Zanotti, Alberto Bottini, +2 authors, Maria Rosa Cappelletti.
Tumour Biol, 2014 Jul 23; 35(9). PMID: 25048969
Review.
Quantitative Gene Expression by Recurrence Score in ER-Positive Breast Cancer, by Age.
Sandra M Swain, Raquel Nunes, +2 authors, Amy P Sing.
Adv Ther, 2015 Nov 28; 32(12). PMID: 26610382    Free PMC article.
A Prospective Comparison of the 21-Gene Recurrence Score and the PAM50-Based Prosigna in Estrogen Receptor-Positive Early-Stage Breast Cancer.
Michael D Alvarado, Che Prasad, +5 authors, Christos J Markopoulos.
Adv Ther, 2015 Nov 28; 32(12). PMID: 26610383    Free PMC article.
Chemotherapy in Premenopausal Breast Cancer Patients.
Ann H Partridge.
Breast Care (Basel), 2015 Dec 22; 10(5). PMID: 26688676    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.
Dissecting the Biological Heterogeneity within Hormone Receptor Positive HER2 Negative Breast Cancer by Gene Expression Markers Identifies Indolent Tumors within Late Stage Disease.
Jyothi S Prabhu, Aruna Korlimarla, +14 authors, T S Sridhar.
Transl Oncol, 2017 Jul 14; 10(4). PMID: 28704710    Free PMC article.
How to Achieve Optimal Care in Early Breast Cancer with 'Less' or 'More' Treatment.
Giuseppe Curigliano.
Breast Care (Basel), 2017 Aug 09; 12(3). PMID: 28785179    Free PMC article.
De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.
G Curigliano, H J Burstein, +52 authors, B Xu.
Ann Oncol, 2017 Aug 26; 28(8). PMID: 28838210    Free PMC article.
Highly Cited.
Gene Expression Profiling in Breast Cancer and Its Effect on Therapy Selection in Early-Stage Breast Cancer.
E Nilüfer Güler.
Eur J Breast Health, 2017 Oct 31; 13(4). PMID: 29082373    Free PMC article.
Review.
Clinical utility of multigene profiling assays in early-stage breast cancer.
M C Chang, L H Souter, +6 authors, Molecular Oncology Advisory Committee.
Curr Oncol, 2017 Nov 02; 24(5). PMID: 29089811    Free PMC article.
Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer.
Volker Möbus, Susanne Hell, Marcus Schmidt.
Geburtshilfe Frauenheilkd, 2017 Nov 03; 77(10). PMID: 29093601    Free PMC article.
Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.
Hege O Ohnstad, Elin Borgen, +11 authors, Bjørn Naume.
Breast Cancer Res, 2017 Nov 16; 19(1). PMID: 29137653    Free PMC article.
Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.
Guillaume Latgé, Christophe Poulet, +2 authors, Guy Jerusalem.
Int J Mol Sci, 2018 Jan 06; 19(1). PMID: 29301303    Free PMC article.
Review.
Optimal duration of adjuvant endocrine therapy: how to apply the newest data.
Kerstin Wimmer, Stephanie Strobl, +5 authors, Michael Gnant.
Ther Adv Med Oncol, 2018 Jan 19; 9(11). PMID: 29344105    Free PMC article.
Review.
Intrinsic molecular subtypes of breast cancers categorized as HER2-positive using an alternative chromosome 17 probe assay.
Neelam V Desai, Vanda Torous, +6 authors, Nadine Tung.
Breast Cancer Res, 2018 Jul 13; 20(1). PMID: 29996866    Free PMC article.
Guideline-concordant chemotherapy in patients with hormone receptor-positive and node-positive, early breast cancer leads to better overall and metastases-free survival with limited benefit in elderly patients.
Clara Taubenhansl, Olaf Ortmann, +2 authors, Monika Klinkhammer-Schalke.
Arch Gynecol Obstet, 2019 Nov 22; 301(2). PMID: 31749031    Free PMC article.
Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial.
Thomas Ruhstaller, Anita Giobbie-Hurder, +27 authors, members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group.
J Clin Oncol, 2018 Nov 27; 37(2). PMID: 30475668    Free PMC article.
Gene Expression Profiling Tests for Early-Stage Invasive Breast Cancer: A Health Technology Assessment.
Ontario Health (Quality).
Ont Health Technol Assess Ser, 2020 Apr 15; 20(10). PMID: 32284770    Free PMC article.
Commercially Available Gene Expression Assays as Predictive Tools for Adjuvant Radiotherapy? A Critical Review.
David Krug, René Baumann, +12 authors, Rolf Sauer.
Breast Care (Basel), 2020 May 14; 15(2). PMID: 32398980    Free PMC article.
Review.
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.
Risk stratification in luminal-type breast cancer: Comparison of Ki-67 with EndoPredict test results.
Aurelia Noske, Sophie-Isabelle Anders, +6 authors, Evelyn Klein.
Breast, 2019 Dec 02; 49. PMID: 31786414    Free PMC article.
Should a Multigene Signature be Used in all Luminal Early Breast Cancers.
Nawale Hajjaji, Yves Marie Robin, Jacques Bonneterre.
Front Oncol, 2019 Jun 20; 9. PMID: 31214499    Free PMC article.
Gene Expression Assays for Early-Stage Hormone Receptor-Positive Breast Cancer: Understanding the Differences.
Ana Tablante Nunes, Deborah E Collyar, Lyndsay N Harris.
JNCI Cancer Spectr, 2017 Dec 11; 1(1). PMID: 31360834    Free PMC article.
Review.
SEOM clinical guidelines in early stage breast cancer (2018).
F Ayala de la Peña, R Andrés, +7 authors, E Ciruelos.
Clin Transl Oncol, 2018 Nov 18; 21(1). PMID: 30443868    Free PMC article.
[Update of the German S3 breast cancer guideline : What is new for pathologists?]
A Lebeau, C Denkert, +2 authors, A Wöckel.
Pathologe, 2019 Mar 09; 40(2). PMID: 30847505
A multiple breast cancer stem cell model to predict recurrence of T1-3, N0 breast cancer.
Yan Qiu, Liya Wang, +8 authors, Hong Bu.
BMC Cancer, 2019 Jul 26; 19(1). PMID: 31340763    Free PMC article.
Concordance between results of inexpensive statistical models and multigene signatures in patients with ER+/HER2- early breast cancer.
Laurence Slembrouck, Isabelle Vanden Bempt, +12 authors, Giuseppe Floris.
Mod Pathol, 2021 Feb 10; 34(7). PMID: 33558657
Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative.
Paolo Giorgi Rossi, Annette Lebeau, +13 authors, ECIBC Contributor Group.
Br J Cancer, 2021 Feb 19; 124(9). PMID: 33597715    Free PMC article.
Review.