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Villegas, Sonia L.; Nekljudova, Valentina; Pfarr, Nicole; Engel, Jutta; Untch, Michael; Schrodi, Simone; Holms, Frank; Ulmer, Hans U.; Fasching, Peter A.; Weber, Karsten E.; Albig, Christian; Heinrichs, Clemens; Marmé, Frederik; Tesch, Hans; Jackisch, Christian; Rezai, Mahdi; Sinn, Peter; Sinn, Bruno V.; Hackmann, John; Kiechle, Marion; Schneeweiss, Andreas; Weichert, Wilko; Denkert, Carsten und Loibl, Sibylle (2021): Therapy response and prognosis of patients with early breast cancer with low positivity for hormone receptors - An analysis of 2765 patients from neoadjuvant clinical trials. In: European Journal of Cancer, Bd. 148: S. 159-170

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Abstract

AIM To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. METHODS We compared negative oestrogen (ER) and progesterone receptor (PR) {\textless}1{\%}, low-positive (ER and/or PR 1-9{\%})~and strong-positive (ER or PR 10-100{\%}) HR-expression in neoadjuvant clinical trial cohorts (n~=~2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS)~and overall survival (OS). We performed RNA sequencing on available tumour tissue samples from patients with low-HR expression (n~=~38). RESULTS Ninety-four (3.4{\%}) patients had low HR-positive tumours, 1769 (64.0{\%}) had strong HR-positive tumours, and 902 (32.6{\%}) had TNBC. There were no significant differences in pCR rates between women with low HR-positive tumours (27.7{\%}) and women with TNBC (35.5{\%}). DFS and DDFS were also not different for DFS, hazard ratio 1.26, 95{\%}-CI (confidence interval) : 0.87-1.83, log-rank test p~=~0.951; for DDFS, hazard ratio 1.17, 95{\%}-CI: 0.78-1.76, log-rank test p~=~0.774. Patients with strong HR-positive tumours had a significantly lower pCR rate (pCR 9.4{\%}; odds ratio 0.38, 95{\%}-CI: 0.23-0.63), but better DFS (hazard ratio 0.48, 95{\%}-CI: 0.33-0.70) and DDFS (hazard ratio 0.49, 95{\%}-CI: 0.33-0.74) than patients with low HR-positive tumours. Molecular subtyping (RNA sequencing) of low HR-positive tumours classified these predominantly into a basal subtype (86.8{\%}). CONCLUSION Low HR-positive, HER2-negative tumours have a similar clinical behaviour to TNBC showing high pCR rates and poor survival and also a basal-like gene expression signature. Patients with low HR-positive tumours should be regarded as candidates for therapy strategies targeting TNBC.

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