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Breast Cancer Res Treat. 2018 Feb;168(1):169-178. doi: 10.1007/s10549-017-4543-7. Epub 2017 Nov 24.

Evaluation of applying IHC4 as a prognostic model in the translational study of Intergroup Exemestane Study (IES): PathIES.

Author information

1
The Institute of Cancer Research, Clinical Trials and Statistics Unit (ICR-CTSU) Section of Clinical Trials, Sir Richard Doll Building, Sutton, SM2 5NG, UK.
2
Department of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.
3
Leeds Institute of Molecular Medicine, University of Leeds, St James's University Hospital, Wellcome Trust Brenner Building, Leeds, LS9 7TF, UK.
4
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, L69 3BX, UK.
5
Department of Pathology, Queen Elizabeth Medical Centre, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK.
6
Department of Oncology, University of Bergen, Haukeland University Hospital, 5021, Bergen, Norway.
7
Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
8
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 ZA, Leiden, Netherlands.
9
Department of Pathology, Herlev and Gentofte Hospital, Copenhagen, Denmark.
10
Department of Medical Oncology, AZ Klina, Braschaat, Belgium.
11
Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
12
Department of Cancer and Surgery, Faculty of Medicine, Imperial College London, Du Cane Road, London, W12 0NN, UK. c.coombes@imperial.ac.uk.

Abstract

BACKGROUND:

Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2-3 years from tamoxifen to exemestane. This PathIES aimed to assess the role of immunohistochemical (IHC)4 score in determining the relative sensitivity to either tamoxifen or sequential treatment with tamoxifen and exemestane.

PATIENTS AND METHODS:

Primary tumour samples were available for 1274 patients (27% of IES population). Only patients for whom the IHC4 score could be calculated (based on oestrogen receptor, progesterone receptor, HER2 and Ki67) were included in this analysis (N = 430 patients). The clinical score (C) was based on age, grade, tumour size and nodal status. The association of clinicopathological parameters, IHC4(+C) scores and treatment effect with time to distant recurrence-free survival (TTDR) was assessed in univariable and multivariable Cox regression analyses. A modified clinical score (PathIEscore) (N = 350) was also estimated.

RESULTS:

Our results confirm the prognostic importance of the original IHC4, alone and in conjunction with clinical scores, but no significant difference with treatment effects was observed. The combined IHC4 + Clinical PathIES score was prognostic for TTDR (P < 0.001) with a hazard ratio (HR) of 5.54 (95% CI 1.29-23.70) for a change from 1st quartile (Q1) to Q1-Q3 and HR of 15.54 (95% CI 3.70-65.24) for a change from Q1 to Q4.

CONCLUSION:

In the PathIES population, the IHC4 score is useful in predicting long-term relapse in patients who remain disease-free after 2-3 years. This is a first trial to suggest the extending use of IHC4+C score for prognostic indication for patients who have switched endocrine therapies at 2-3 years and who remain disease-free after 2-3 years.

KEYWORDS:

Aromatase; Breast cancer; Prognosis

PMID:
29177605
PMCID:
PMC5847042
DOI:
10.1007/s10549-017-4543-7
[Indexed for MEDLINE]
Free PMC Article

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