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. 2022 Aug 5;23(15):8716.
doi: 10.3390/ijms23158716.

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist's Decision on Systemic Therapy in a Real-World Setting

Ramona Erber  1   2 , Miriam Angeloni  1   2 , Robert Stöhr  1   2 , Michael P Lux  3 , Daniel Ulbrich-Gebauer  4 , Enrico Pelz  4 , Agnes Bankfalvi  5 , Kurt W Schmid  5 , Robert F H Walter  5   6 , Martina Vetter  7 , Christoph Thomssen  7 , Doris Mayr  8 , Frederick Klauschen  8 , Peter Sinn  9 , Karl Sotlar  8   10 , Katharina Stering  10 , Albrecht Stenzinger  11 , Marius Wunderle  2   12 , Peter A Fasching  2   12 , Matthias W Beckmann  2   12 , Oliver Hoffmann  13 , Rainer Kimmig  13 , Nadia Harbeck  14 , Rachel Wuerstlein  14 , Fulvia Ferrazzi  1   2   15 , Arndt Hartmann  1   2
Affiliations

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist's Decision on Systemic Therapy in a Real-World Setting

Ramona Erber et al. Int J Mol Sci. .

Abstract

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.

Keywords: IHC; PAM50; Prosigna; breast cancer; chemotherapy; immunohistochemistry; multigene expression analysis; tumor grade.

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Conflict of interest statement

P.A.F. has received honoraria from Roche, Pfizer, Novartis, and Celgene. His institution conducts research for Novartis, Cepheid, and BioNTech. A.H. has received honoraria for lectures or consulting/advisory boards for Abbvie, AstraZeneca, Biontech, BMS, Boehringer Ingelheim, Cepheid, Diaceutics, Illumina, Ipsen, Janssen, Lilly, MSD, NanoString, Novartis, Qiagen, QUIP GmbH, Roche, 3DHistotech. R.E. has received honoraria from Roche, Eisai, Pfizer, Mindpeak, AstraZeneca, and Novartis and travel grants from BioNTech. The institution of A.H. and R.E. conducts research for AstraZeneca, Roche, Janssen-Cilag, Zytomed Systems, NanoString Technologies, Veracyte, Biocartis, Novartis, Cepheid, and BioNTech. N.H. reports honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi-Sankyo, Exact Sciences, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz/Hexal, and Seattle Genetics. R.W. served as advisor/consultant/speaker for and/or received travel grants by Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Daiichi-Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Tesaro Bio, Teva, Veracyte, and Viatris. O.H. received honoraria for lectures or consulting/advisory boards for Riemser, Roche, AstraZeneca, Amgen, Pfizer, Eisai, Hexal, MSD, Novartis, SeaGen, and Daiichi-Sankyo. M.P.L. reports honoraria for advisory boards for Lilly, AstraZeneca, MSD, Novartis, Pfizer, Gilead, Eisai, Exact Sciences, Daiichi-Sankyo, Grünenthal, Pierre Fabre, PharmaMar, and Roche; honoraria for lectures for Lilly, Roche, MSD, Novartis, Pfizer, Exact Sciences, Daiichi-Sankyo, Grünenthal, AstraZeneca, and Eisai; editorial board for medac; travel grants for Roche, and Pfizer. The other authors have nothing to declare.

Figures

Figure 1
Figure 1
Distribution of Prosigna® subtypes across (A) local IHC subtypes, (B) local IHC+G subtypes, (C) C1 IHC subtypes, (D) C1 IHC+G subtypes, (E) C6 IHC subtypes, (F) C6 IHC+G subtypes. HER2_enr = HER2-enriched; IHC = immunohistochemistry; IHC+G = immunohistochemistry + tumor grade; LumA = Luminal A; LumB = Luminal B.
Figure 2
Figure 2
Distribution of Prosigna® subtypes across (A) Prosigna® risk of recurrence and (B) Prosigna® risk groups. HER2_enr = HER2-enriched; LumA = Luminal A; LumB = Luminal B.
Figure 3
Figure 3
Distribution of Prosigna® risk groups across local surrogate (A) IHC subtypes and (B) IHC+G subtypes. IHC = immunohistochemistry; IHC+G = immunohistochemistry + tumor grade; LumA = Luminal A; LumB = Luminal B.
Figure 4
Figure 4
Distribution of tumor board recommended across the different Prosigna® subtypes. HER2_enr = HER2-enriched; LumA = Luminal A; LumB = Luminal B; Th. = therapy.
Figure 5
Figure 5
Influence of Prosigna® results on treatment decision for locally assessed IHC and IHC+G surrogate subtypes. (A) Recommended therapy within locally assessed IHC surrogate subtypes and (B) distribution of Prosigna® subtype within the subset of Luminal A-like IHC subtypes that were recommended towards adjuvant chemotherapy and endocrine therapy. (C) Recommended therapy within locally assessed IHC+G surrogate subtypes and (D) distribution of Prosigna® subtype within the subset of Luminal A-like IHC+G subtypes that were recommended towards adjuvant chemotherapy and endocrine therapy. Colour intensity reflects Prosigna® risk group. IHC = immunohistochemistry; IHC+G = immunohistochemistry + tumor grade; LumA = Luminal A; LumB = Luminal B; Th. = therapy.
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