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

Abstract

Purpose: The 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).

Methods: Patients 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.

Results: Overall, 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).

Conclusion: The 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.

Keywords: Biopsy; Breast cancer; HER2 receptor; Hormone receptor; Metastatic disease; Subtype.

Conflict of interest statement

MM, KI, and AHW report grant of the Netherlands Organization for Health Research and Development (ZonMw: 80–82500-98–8003) and financial support by Novartis BV, Roche, Pfizer, and Eli Lilly, as listed in the funding section. IV reports grant from Pfizer. SG reports institutional grants from Novartis BV, Roche, Pfizer, Eli Lilly, and Daiichi Sankyo and personal fees from AstraZeneca. VTH reports grants and personal fees from Roche, grants and personal fees from Novartis, grants and personal fees from Pfizer, grants and personal fees from Lilly, personal fees from Accord Healthcare, grants from AstraZeneca, grants from Eisai, and grants from Daiichi Sankyo. All remaining authors have declared no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Factors associated with undergoing a biopsy of a metastatic site at time of ABC diagnosis, by multivariable logistic regression analysis. aIn case of two or more primary tumors, the subtype of the first primary tumor is reported. *Not statistically significant, but borderline (P< 0.10), ** P< 0.05, *** P< 0.001
Fig. 2
Fig. 2
Subtype of the metastatic lesion per primary tumor subtype (n = 748)
Fig. 3
Fig. 3
Factors associated with subtype discordance between the primary tumor and the metastatic site at time of ABC diagnosis, by multivariable logistic regression analysis. *Not statistically significant, but borderline (P< 0.10), ** P< 0.05, *** P< 0.001
Fig. 4
Fig. 4
First treatment choice for concordant and discordant subtype of metastatic site in primary HR + /HER2 + subtype

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