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Combined quantitative measures of ER, PR, HER2, and KI67 provide more prognostic information than categorical combinations in luminal breast cancer.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Abubakar, Mustapha 
Ali, H Raza 
Blows, Fiona 
Lissowska, Jolanta 

Abstract

Although most women with luminal breast cancer do well on endocrine therapy alone, some will develop fatal recurrence thereby necessitating the need to prospectively determine those for whom additional cytotoxic therapy will be beneficial. Categorical combinations of immunohistochemical measures of ER, PR, HER2, and KI67 are traditionally used to classify patients into luminal A-like and B-like subtypes for chemotherapeutic reasons, but this may lead to the loss of prognostically relevant information. Here, we compared the prognostic value of quantitative measures of these markers, combined in the IHC4-score, to categorical combinations in subtypes. Using image analysis-based scores for all four markers, we computed the IHC4-score for 2498 patients with luminal breast cancer from two European study populations. We defined subtypes (A-like (ER + and PR + : and HER2- and low KI67) and B-like (ER + and/or PR + : and HER2 + or high KI67)) by combining binary categories of these markers. Hazard ratios and 95% confidence intervals for associations with 10-year breast cancer-specific survival were estimated in Cox proportional-hazard models. We accounted for clinical prognostic factors, including grade, tumor size, lymph-nodal involvement, and age, by using the PREDICT-score. Overall, Subtypes [hazard ratio (95% confidence interval) B-like vs. A-like = 1.64 (1.25-2.14); P-value < 0.001] and IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.32 (1.20-1.44); P-value < 0.001] were prognostic in univariable models. However, IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.24 (1.11-1.37); P-value < 0.001; likelihood ratio chi-square (LRχ2) = 12.5] provided more prognostic information than Subtype [hazard ratio (95% confidence interval) B-like vs. A-like = 1.38 (1.02-1.88); P-value = 0.04; LRχ2 = 4.3] in multivariable models. Further, higher values of the IHC4-score were associated with worse prognosis, regardless of subtype (P-heterogeneity = 0.97). These findings enhance the value of the IHC4-score as an adjunct to clinical prognostication tools for aiding chemotherapy decision-making in luminal breast cancer patients, irrespective of subtype.

Description

Keywords

Adult, Aged, Biomarkers, Tumor, Breast Neoplasms, Female, Humans, Ki-67 Antigen, Middle Aged, Prognosis, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone

Journal Title

Mod Pathol

Conference Name

Journal ISSN

0893-3952
1530-0285

Volume Title

32

Publisher

Elsevier BV

Rights

All rights reserved
Sponsorship
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research Uk (None)
Cancer Research UK (unknown)
Cancer Research UK (60098573)
Cancer Research UK (unknown)
Cancer Research UK (CB4140)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
European Commission (223175)
Cancer Research UK (5260)
Breast Cancer Now (None)
Cancer Research Uk (None)
Cancer Research UK (A25117)
Cancer Research UK (C14303/A17197)
Cancer Research UK (C9545/A29580_do not transfer)
Cancer Research UK (25815)