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

Villegas SL, Nekljudova V, Pfarr N, Engel J, Untch M, Schrodi S, Holms F, Ulmer HU, Fasching P, Weber KE, Albig C, Heinrichs C, Marmé F, Hartmann A, Hanusch C, Schmitt WD, Huober J, Lederer B, van Mackelenbergh M, Tesch H, Jackisch C, Rezai M, Sinn P, Sinn BV, Hackmann J, Kiechle M, Schneeweiss A, Weichert W, Denkert C, Loibl S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 148

Pages Range: 159-170

DOI: 10.1016/j.ejca.2021.02.020

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) <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.

Authors with CRIS profile

Involved external institutions

Rotkreuzklinikum München Germany (DE) Universitätsklinikum Mannheim Germany (DE) Luisenkrankenhaus Düsseldorf Germany (DE) Technische Universität München (TUM) Germany (DE) Klinikum Mittelbaden Baden-Baden Balg Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universität Ulm Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) HELIOS Kliniken Germany (DE) Marien Hospital Witten Germany (DE) Klinikum der Universität München Germany (DE) St. Barbara-Klinik Hamm Germany (DE) Sana Kliniken AG Germany (DE) GBG Forschungs GmbH (German Breast Group) Germany (DE) Klinikum rechts der Isar Germany (DE) Agaplesion Markus Krankenhaus Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE)

How to cite

APA:

Villegas, S.L., Nekljudova, V., Pfarr, N., Engel, J., Untch, M., Schrodi, S.,... Loibl, S. (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. European Journal of Cancer, 148, 159-170. https://doi.org/10.1016/j.ejca.2021.02.020

MLA:

Villegas, Sonia L., et al. "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." European Journal of Cancer 148 (2021): 159-170.

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