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

Julia Van Steenhoven,Alex Imholz,Jelle Wesseling,Johanna Timmer-Bonte,Sabine Siesling,Anne Kuijer,Emiel Rutgers,Thijs Van Dalen,Charlotte Blanken,Marieke Straver,Paul Van Diest,Joost Van Gorp,Sjoerd Elias,Tineke Smilde,Peter Nieboer

doi:10.3390/genes9050261

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.

Highlights

The identification of intrinsic (“molecular”) subtypes of human breast cancer tumors byPerou et al 15 years ago catalyzed the concept of individualized cancer therapy [1]
On adjuvant chemotherapy decision-making in patients with surgically-treated ER+ breast cancer, conventional pathology data and gene expression read-outs were obtained between 1 January
When Ki67 expression or Bloom Richardson (BR) grade was used in addition to routine pathology and compared to molecular subtyping to differentiate between luminal A/B type cancers, concordance was low

Summary

Introduction

The identification of intrinsic (“molecular”) subtypes of human breast cancer tumors by. Perou et al 15 years ago catalyzed the concept of individualized cancer therapy [1]. The majority of early stage breast cancer patients are diagnosed with an estrogen receptor positive (ER+) and HER2 receptor negative (HER2−) disease, associated with favorable outcomes, and patients benefit from endocrine therapy. HER2-driven and basal-like tumors are more aggressive breast cancer subtypes, and patients are sensitive to chemotherapy. The population diagnosed with ER+/HER2− (luminal type) disease is highly heterogeneous as patients with similar clinicopathological features can have strikingly different outcomes. In patients diagnosed with luminal A type disease, the additional value of chemotherapy over endocrine is questionable, whereas chemotherapy seems to be of more benefit to patients with luminal B tumors [2,3,4]

Methods

Results

Conclusion