Frailty-gradient Risk of Mortality Comparing Primary Endocrine Therapy and Surgery in Treating Women with Early Breast Cancer

Background: Primary endocrine therapy (PET) has been increasingly used as an alternative to surgery in older women with early-stage breast cancer due to concerns of frailty or comorbidity, resulting in unfit for surgery. However, evidence on the clinical effectiveness of PET in frail women with breast cancer is limited.

Objectives: This cohort study compared all-cause and breast cancer specific mortality associated with PET and surgery in women with breast cancer of various frailty levels and age groups.

Methods: Women aged ≥50 years with a newly diagnosed, early-stage breast cancer were identified from Clinical Practice Research Datalink (Gold and Aurum) linking to Hospital Episode Statistics, Cancer Registry, and national death registration from 2000 to 2016 in England and followed from the date of diagnosis to death before 2019. In both older (≥70 years) and younger (50-69 years) groups, patients were stratified by frailty levels (low, intermediate and high), and propensity scores (from age, Hospital Risk Frailty Score and Charlson Comorbidity Index and Index of Multiple Deprivation), were used to match patients receiving PET or surgery by inverse probability of weight. All-cause and breast cancer specific mortality were analysed by Kaplan-Meier survival analysis and Cox regression, adjusted for the above variables as doubly robust estimations, and presented in Hazard Ratio (HR) and 95% confidence intervals (95%CI).

Results: Most patients were diagnosed at 50-69 years (61% of 58,804). The proportion of receiving PET was lower in the younger than older group (7% vs. 30%). The 5-year breast cancer-specific mortality was lower in surgery than PET in both younger (30% vs. 36%) and older (44% vs. 50%). PET was associated with a significantly higher risk of all-cause and breast cancer-specific mortality than surgery in patients with low and intermediate frailty. However, there is no significant difference in breast cancer specific mortality for patients with high frailty in younger (HR: 1.59; 95%CI: 0.50, 5.09) and older (HR: 1.3; 95%CI: 0.92, 1.84) groups.

Conclusions: Many women with breast cancer receiving PET may potentially be suitable for surgery. Although surgery demonstrated a survival benefit in treating early-stage breast cancer compared with PET regardless of age, PET is not inferior to surgery for patients with a high level of frailty.