Earl, Helena, Provenzano, Elena, Abraham, Jean, Dunn, Janet A., Vallier, Anne-Laure, Gounaris, Ioannis and Hiller, Louise (2015) Neoadjuvant trials in early breast cancer : pathological response at surgery and correlation to longer term outcomes – what does it all mean? BMC Medicine, 13 (1). 234. doi:10.1186/s12916-015-0472-7

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Abstract

Background:
Neoadjuvant breast cancer trials are important for speeding up the introduction of new treatments for patients with early breast cancer and for the highly productive translational research which they facilitate. Meta-analysis of trial data shows clear correlation between pathological response at surgery after neoadjuvant chemotherapy and longer-term outcomes at an individual patient level. However, this does not appear to be present on individual trial level analysis, when correlating improved outcome for the investigational arm for the primary endpoint (pathological response) with longer-term outcomes.

Discussion:
The correlation between pathological response and longer-term outcomes in trials is dependent on many factors. These include definitions of pathological response, both complete and partial; assessment methods for pathological response at surgery; subtype and prognosis of breast cancer at diagnosis; number of patients recruited; adjuvant treatments; the mechanism of action of the investigational drug; the length of follow-up at the time of reporting; the definitions used in longer-term outcomes analysis; clonal heterogeneity; and new adaptive trial designs with additional neo/adjuvant treatments. Future developments of neoadjuvant breast cancer trials are discussed. With so many factors influencing the correlation of longer-term outcomes for trial-level data, we conclude that the main focus of neoadjuvant trials should remain the primary endpoint of pathological response.

Summary:
Neoadjuvant breast cancer trials are very important investigational studies that will continue to increase our understanding of the disease and offer the potential of more rapid introduction of new treatments for women with high-risk early breast cancer. In the future, we are likely to see both novel trial designs adopted in the neoadjuvant context and modifications of neo/adjuvant treatments for pathological non-responders within clinical trials. Both of these have the intention of improving longer-term outcomes for patients who do not have a good pathological response to first-line neoadjuvant treatment. If successful, these developments are likely to reduce further any positive correlation between pathological response and longer-term outcomes.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Breast -- Cancer -- Treatment, Clinical trials
Journal or Publication Title:	BMC Medicine
Publisher:	BioMed Central Ltd.
ISSN:	1741-7015
Official Date:	14 May 2015
Dates:	Date Event 14 May 2015 Published 1 September 2015 Accepted 14 May 2015 Submitted
Volume:	13
Number:	1
Article Number:	234
DOI:	10.1186/s12916-015-0472-7
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	NIHR Cambridge Biomedical Research Centre

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