Survival Outcomes in Older Women with Oestrogen-Receptor-Positive Early-Stage Breast Cancer: Primary Endocrine Therapy vs. Surgery by Comorbidity and Frailty Levels

Yubo Wang; Douglas Steinke; Sean P Gavan; Teng-Chou Chen; Matthew J Carr; Darren M Ashcroft; Kwok-Leung Cheung; Li-Chia Chen

doi:10.3390/cancers16040749

Survival Outcomes in Older Women with Oestrogen-Receptor-Positive Early-Stage Breast Cancer: Primary Endocrine Therapy vs. Surgery by Comorbidity and Frailty Levels

Cancers (Basel). 2024 Feb 11;16(4):749. doi: 10.3390/cancers16040749.

Authors

Yubo Wang¹, Douglas Steinke¹, Sean P Gavan², Teng-Chou Chen¹, Matthew J Carr¹, Darren M Ashcroft^{1

3}, Kwok-Leung Cheung⁴, Li-Chia Chen¹

Affiliations

¹ Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
² Manchester Centre for Health Economics, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.
³ NIHR Greater Manchester Patient Safety Research Collaboration (PSRC), The University of Manchester, Manchester M13 9PT, UK.
⁴ Royal Derby Hospital Centre, School of Medicine, University of Nottingham, Uttoxeter Road, Derby DE22 3DT, UK.

Abstract

Primary endocrine therapy (PET) offers non-surgical treatment for older women with early-stage breast cancer who are unsuitable for surgery due to frailty or comorbidity. This research assessed all-cause and breast cancer-specific mortality of PET vs. surgery in older women (≥70 years) with oestrogen-receptor-positive early-stage breast cancer by frailty and comorbidity levels. This study used UK secondary data to analyse older female patients from 2000 to 2016. Patients were censored until 31 May 2019 and grouped by the Charlson comorbidity index (CCI) and hospital frailty risk score (HFRS). Cox regression models compared all-cause and breast cancer-specific mortality between PET and surgery within each group, adjusting for patient preferences and covariates. Sensitivity analyses accounted for competing risks. There were 23,109 patients included. The hazard ratio (HR) comparing PET to surgery for overall survival decreased significantly from 2.1 (95%CI: 2.0, 2.2) to 1.2 (95%CI: 1.1, 1.5) with increasing HFRS and from 2.1 (95%CI: 2.0, 2.2) to 1.4 (95%CI 1.2, 1.7) with rising CCI. However, there was no difference in BCSM for frail older women (HR: 1.2; 0.9, 1.9). There were no differences in competing risk profiles between other causes of death and breast cancer-specific mortality with PET versus surgery, with a subdistribution hazard ratio of 1.1 (0.9, 1.4) for high-level HFRS (p = 0.261) and CCI (p = 0.093). Given limited survival gains from surgery for older patients, PET shows potential as an effective option for frail older women with early-stage breast cancer. Despite surgery outperforming PET, surgery loses its edge as frailty increases, with negligible differences in the very frail.

Keywords: comorbidities; early-stage breast cancer; frailty; older postmenopausal women; primary endocrine therapy; surgery.

Grants and funding

This study was funded by the NIHR Greater Manchester Patient Safety Research Collaboration (PSRC), Grant No. NIHR204295. Wang Y. received a joint scholarship from the University of Manchester and the China Scholarship Council for his PhD study from 2018 to 2021.