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

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

Abstract

Background: 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. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. Results: Three 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. Conclusions: Chemotherapy 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 Registration: ISRCTN 46099296.

Citation

Ring, A., Battisti, N. M. L., Reed, M. W. R., Herbert, E., Morgan, J. L., Bradburn, M., Walters, S. J., Collins, K. A., Ward, S. E., Holmes, G. R., Burton, M., Lifford, K., Edwards, A., Robinson, T. G., Martin, C., Chater, T., Pemberton, K. J., Brennan, A., Cheung, K. L., Todd, A., …on behalf of the Age Gap TMG. (2021). 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. British Journal of Cancer, 125, 209-219. https://doi.org/10.1038/s41416-021-01388-9

• Journal Article Type: Article
• Acceptance Date: Mar 31, 2021
• Online Publication Date: May 10, 2021
• Publication Date: Jul 20, 2021
• Deposit Date: May 13, 2021
• Publicly Available Date: May 13, 2021
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 125
• Pages: 209-219
• DOI: https://doi.org/10.1038/s41416-021-01388-9
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/5528807
• Publisher URL: https://www.nature.com/articles/s41416-021-01388-9
• Additional Information: Received: 29 October 2020; Revised: 20 February 2021; Accepted: 31 March 2021; First Online: 10 May 2021; : Ethics approval (NRES Committee London South East REC—IRAS: 12 LO 1808) and research governance approval were obtained. All patients (or their proxies, if cognitively impaired) gave written informed consent. The study was performed in accordance with the Declaration of Helsinki.; : Not applicable.; : The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.; : The authors declare no competing interests. Professors Stephen Walters and Thompson Robinson are National Institute for Health Research (NIHR) Senior Investigators, Jenna Morgan is a NIHR Clinical Lecturer and Kate Lifford is funded by the NIHR as part of this project. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care.; : The study was sponsored by Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust. Clinical Research Office, First Floor ‘C' Block, Doncaster Royal Infirmary, Armthorpe Road, Doncaster, DN2 5LT, UK. This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-1209-10071). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.