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Genes 2018, 9(5), 261; https://doi.org/10.3390/genes9050261

Conventional Pathology Versus Gene Signatures for Assessing Luminal A and B Type Breast Cancers: Results of a Prospective Cohort Study

1
Department of Surgery, Diakonessenhuis Utrecht, 3582 KE Utrecht, The Netherlands
2
Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
3
Department of Pathology, Diakonessenhuis Utrecht, 3582 KE Utrecht, The Netherlands
4
Department of Surgery, Haaglanden Medical Center, 2512 VA The Hague, The Netherlands
5
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands
6
Department of Pathology, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
7
Department of Surgery, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
8
Department of Medical Oncology, Alexander-Monro Hospital, 3723 MB Bilthoven, The Netherlands
9
Department of Medical Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
10
Department of Medical Oncology, Wilhelmina Hospital Assen, 9401 RK Assen, The Netherlands
11
Department of Medical Oncology, Jeroen Bosch Hospital, 5223 GZ 's-Hertogenbosch, The Netherlands
12
Department of Medical Oncology, Deventer Hospital, 7416 SE Deventer, The Netherlands
13
Department of Surgery, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
14
Department of Research, Netherlands Comprehensive Cancer Organization, 3511 DT Utrecht, The Netherlands
15
Department of Health Technology and Services Research, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, 7522 NB Enschede, The Netherlands
*
Author to whom correspondence should be addressed.
Received: 4 April 2018 / Revised: 7 May 2018 / Accepted: 16 May 2018 / Published: 17 May 2018
(This article belongs to the Section Human Genomics and Genetic Diseases)
Full-Text   |   PDF [254 KB, uploaded 22 May 2018]

Abstract

In this study, in estrogen receptor positive (ER+) early stage breast cancer patients who were considered candidates for 70-gene signature (70-GS, “MammaPrint”) use, we compared molecular subtyping (MS) based on the previously validated 80-gene signature (80-GS, “BluePrint”) versus surrogate pathological subtyping (PS). Between 1 January 2013 and 31 December 2015, 595 clinical intermediate risk ER+ early stage breast cancer patients were enrolled. Hormone receptor (HR) and HER2 receptor status were determined by conventional pathology using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Ki67 was assessed in a subset of patients. The overall concordance between PS and MS for luminal type cancers (A and B together) was 98%. The concordance between PS and MS for luminal A and luminal B type cancers based on the Bloom Richardson histological grade (BR) (n = 586) or Ki67 (n = 185) was low: 64% (Kappa 0.20 [95% CI 0.11–0.28]) and 65% (Kappa 0.22 [95% CI 0.062–0.37]), respectively. In this prospective study (NCT02209857) of a selection of ER+ and predominantly HER2− early-stage breast cancer patients, the additional ability of the 80-GS to distinguish between luminal, HER2-type and basal-like cancers was inherently very limited. The distinction of luminal-type tumors into A and B according to Ki67 status or BR grade versus the 70-GS revealed poor concordance. View Full-Text
Keywords: breast cancer; molecular subtyping; local pathology; 80-gene signature; 70-gene signature; Ki67 breast cancer; molecular subtyping; local pathology; 80-gene signature; 70-gene signature; Ki67
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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van Steenhoven, J.E.; Kuijer, A.; van Diest, P.J.; van Gorp, J.M.; Straver, M.; Elias, S.G.; Wesseling, J.; Rutgers, E.; Timmer-Bonte, J.N.; Nieboer, P.; Smilde, T.J.; Imholz, A.; Blanken, C.F.; Siesling, S.; van Dalen, T. Conventional Pathology Versus Gene Signatures for Assessing Luminal A and B Type Breast Cancers: Results of a Prospective Cohort Study. Genes 2018, 9, 261.

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