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.

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: Sonia L Villegas, Valentina Nekljudova, Nicole Pfarr, Jutta Engel, Michael Untch, Simone Schrodi, Frank Holms, Hans U Ulmer, Peter A Fasching, Karsten E Weber, Christian Albig, Clemens Heinrichs, Frederik Marmé, Arndt Hartmann, Claus Hanusch, Wolfgang D Schmitt, Jens Huober, Bianca Lederer, Marion van Mackelenbergh, Hans Tesch, Christian Jackisch, Mahdi Rezai, Peter Sinn, Bruno V Sinn, John Hackmann, Marion Kiechle, Andreas Schneeweiss, Wilko Weichert, Carsten Denkert, Sibylle Loibl
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 148 Pg. 159-170 (05 2021) ISSN: 1879-0852 [Electronic] England
• PMID: 33743484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Receptors, Estrogen
• Receptors, Progesterone
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (genetics)
• Chemotherapy, Adjuvant (mortality)
• Female
• Follow-Up Studies
• Gene Expression Profiling
• Humans
• Middle Aged
• Neoadjuvant Therapy (mortality)
• Prognosis
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Remission Induction
• Survival Rate
• Triple Negative Breast Neoplasms (drug therapy, genetics, mortality, pathology)