Kantonsspital St.Gallen
login

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

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 Marme, 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

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.
   
citation Villegas S L, Nekljudova V, Pfarr N, Engel J, Untch M, Schrodi S, Holms F, Ulmer H U, Fasching P A, Weber K E, Albig C, Heinrichs C, Marme F, Hartmann A, Hanusch C, Schmitt W D, Huober J, Lederer B, van Mackelenbergh M, Tesch H, Jackisch C, Rezai M, Sinn P, Sinn B V, Hackmann J, Kiechle M, Schneeweiss A, Weichert W, Denkert C, Loibl S. 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. Eur J Cancer 2021; 148:159-170.
   
type journal paper/review (English)
date of publishing 18-03-2021
journal title Eur J Cancer (148)
ISSN electronic 1879-0852
pages 159-170
PubMed 33743484
DOI 10.1016/j.ejca.2021.02.020