Skip to main content

Research Repository

Advanced Search

Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer

Rakha, Emad A.; Agarwal, Devika; Green, Andrew R.; Ashankyty, Ibraheem; Ellis, Ian O.; Ball, Graham; Alaskandarany, Mohammed A.


Professor of Breast Cancer Pathology

Devika Agarwal

Ibraheem Ashankyty

Graham Ball

Mohammed A. Alaskandarany



Multigene assay is recommended currently for prognostic stratification of the clinically indeterminate group of breast cancer (BC) patients defined as lymph node (LN)?negative, oestrogen receptor (ER)?positive, HER2?negative (LN?/ER+/HER2?) to determine the use of chemotherapy. However, this cohort, comprising approximately 40% of BC, is not a homogeneous group and shows variable outcome. This study aims to determine the prognostic value of routinely assessed variables, singly and in combination, in LN?/ER+/HER2? BC patients.

Methods and results

A total of 830 LN?/ER+/HER2? chemotherapy?naive BCs were investigated. The prognostic value of histological grade, tumour size, lymphovascular invasion (LVI), progesterone receptor (PgR) and Ki67 labelling index (Ki67LI) was assessed. In this series, only 25% of patients received hormone therapy. Median follow?up was 172 months. In the whole cohort, tumour grade, size, LVI, PgR and Ki67LI were correlated highly with outcome in a time?dependent manner. The outcome of this group varied widely from 97% (20% of cases) to 50% survival rate after 10?year follow?up using a combination of these markers. A prognostic index (Nottingham Px) incorporating grade, size, PgR and Ki67LI, was developed. The index can stratify the whole cohort robustly as well as the higher?risk subgroup (NPI score >3.4) into distinct prognostic classes.


Current routinely assessed variables can provide additional prognostic information in LN?/ER+/HER2? BC. The proposed (Nottingham Px) index can stratify the BC clinically indeterminate group of patients into excellent and poor prognostic subgroups and can be used to identify reliably patients for systemic chemotherapy or further multigene prognostic testing. Performance of prognostic variables in these tumours is time?dependent, and should be considered in future studies.


Rakha, E. A., Agarwal, D., Green, A. R., Ashankyty, I., Ellis, I. O., Ball, G., & Alaskandarany, M. A. (2017). Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer. Histopathology, 70(4), 622-631. doi:10.1111/his.13108

Journal Article Type Article
Acceptance Date Oct 24, 2016
Online Publication Date Dec 28, 2016
Publication Date 2017-03
Deposit Date Oct 15, 2018
Journal Histopathology
Print ISSN 0309-0167
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 70
Issue 4
Pages 622-631
Keywords breast carcinoma; Oncotype DX; prognostic classifications
Public URL
Publisher URL