The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry

Marissa Meegdes,Jolien Tol,Ingeborg J H Vriens,Birgit E P J Vriens,Loes F S Kooreman,Kirsten N A Aaldering,M Wouter Dercksen,Manon J A E Pepels,Linda M H Van De Winkel,Agnes J Van De Wouw,Frans L G Erdkamp,Vivianne C G Tjan-Heijnen,Khava I E Ibragimova,Sandra M E Geurts,Dorien J A Lobbezoo,Marjolein L Smidt,Joan B Heijns,Ananda Hochstenbach-Waelen,Natascha A J B Peters

doi:10.1007/s10549-021-06472-5

Abstract

PurposeThe hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the main parameters in guiding systemic treatment choices in breast cancer, but can change during the disease course. This study aims to evaluate the biopsy rate and receptor subtype discordance rate in patients diagnosed with advanced breast cancer (ABC).MethodsPatients diagnosed with ABC in seven hospitals in 2007–2018 were selected from the SOutheast Netherlands Advanced BREast cancer (SONABRE) registry. Multivariable logistic regression analyses were performed to identify factors influencing biopsy and discordance rates.ResultsOverall, 60% of 2854 patients had a biopsy of a metastatic site at diagnosis. One of the factors associated with a reduced biopsy rate was the HR + /HER2 + primary tumor subtype (versus HR + /HER2- subtype: OR = 0.68; 95% CI: 0.51–0.90). Among the 748 patients with a biopsy of the primary tumor and a metastatic site, the overall receptor discordance rate was 18%. This was the highest for the HR + /HER2 + primary tumor subtype, with 55%. In 624 patients with metachronous metastases, the HR + /HER2 + subtype remained the only predictor significantly related to a higher discordance rate, irrespective of prior (neo-)adjuvant therapies (OR = 7.49; 95% CI: 3.69–15.20).ConclusionThe HR + /HER2 + subtype has the highest discordance rate, but the lowest biopsy rate of all four receptor subtypes. Prior systemic therapy was not independently related to subtype discordance. This study highlights the importance of obtaining a biopsy of metastatic disease, especially in the HR + /HER2 + subtype to determine the most optimal treatment strategy.

Highlights

The systemic therapy choice in patients diagnosed with advanced—metastatic—breast cancer (ABC) is primarily based on the receptor subtype
A more recent period of ABC diagnosis was associated with a higher biopsy rate: 67% in 2016–2018 compared with 51% in 2007–2009 (OR = 2.14; 95% CI: 1.70–2.70) (Fig. 1)
An independent higher biopsy rate of distant disease was further observed in younger patients (56–75 years versus > 75 years: OR = 1.80; 95% CI: 1.48–2.19; ≤ 55 years versus > 75 years: OR = 2.20; 95% CI: 1.74–2.78), a metastatic site other than bone-only (e.g., for soft tissue only and for visceral disease only (OR = 2.73; 95% CI: 2.04–3.64)), and a longer Metastatic-free interval (MFI) time compared with de novo ABC (e.g., MFI 3–24 months (OR = 1.60; 95% CI: 1.22–2.10) and MFI ≥ 60 months (OR = 4.05; 95% CI: 3.18–5.15))

Summary

Introduction

The systemic therapy choice in patients diagnosed with advanced—metastatic—breast cancer (ABC) is primarily based on the receptor subtype. These options have included mTOR, PI3K, and CDK4/6 inhibitors for patients with HR + /HER2- disease [1,2,3], HER2-targeted therapies for HER2 + disease [4,5,6,7,8], PARP inhibitors for patients with BRCA1/2 mutated, HER2-negative disease [9], and checkpoint inhibitors for PD-L1-positive TN disease [10] Following these developments, it has become increasingly important to determine the receptor subtype of the tumor in guiding systemic treatment choices.

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