Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer

Alistair Ring ,Geoffrey R Holmes ,Chris Holcombe ,Riccardo A Audisio ,Adrian Edwards ,Esther Herbert ,Jacqui Gath ,Nicolò Matteo Luca Battisti ,Alan Brennan ,Kieran Horgan ,Annaliza Todd ,Sue Ward ,Charlene Martin ,Alastair Thompson ,Karen Collins ,Kate Lifford ,Kwok-Leung Cheung ,Maria Burton ,Richard Simcock ,Matthew Hatton ,Jenna Morgan ,Matthew C Winter ,Deirdre Revell ,Juliet Wright ,Margot Gosney ,Jay Naik ,Michael Bradburn ,Tim Chater ,Thompson G Robinson ,Tracey Green ,Malcolm Reed ,Stephen J Walters ,Kirsty Pemberton ,Rishi Parmeshwar ,Lynda Wyld

doi:10.1038/s41416-021-01388-9

Abstract

BackgroundChemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy.MethodsA multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage.ResultsThree thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed.ConclusionsChemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient.Trial RegistrationISRCTN 46099296

Highlights

Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals
This study represents one of the largest prospective cohort studies conducted in older women with breast cancer and provides valuable data on tumour characteristics and health of older EBC patients
There remained a substantial proportion of high risk, fit patients, with a high relapse risk in their expected lifetime

Summary

Introduction

Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. METHODS: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed. While there have been many high-quality randomised clinical trials

Methods

Results

Conclusion