Defer surgery in operable breast cancer: how long is too long?

Purpose: The aim of this meta-analysis was to evaluate outcomes of surgery compared to primary endocrine therapy (PET) in patients with non-advanced, operable invasive breast cancer, and to determine if PET as initial therapy may safely postpone surgery.

Methods: The MEDLINE, EMBASE, PubMed, and Cochrane Library were searched from database inception to July 2020 to identify eligible studies. Inclusion criteria were experimental or observational studies with at least one arm treated with PET and a second arm treated with surgery with or without PET. Local recurrence or progression of disease was defined as either failure of non-operative management (tumor failing to decrease in size and/or continuous local or distant tumor growth) or relapse of breast tumor after tumor downsizing following PET. Effect estimates were expressed in hazard ratio and 95% confidence intervals (HR (95% CI)).

Results: The analysis included six studies with 1499 unique patients. The median time to local progression of disease was 2.3 years. Patients treated with PET alone without surgery had a higher risk of local recurrence and or progression [HR (95% CI): 1.76 (1.33, 2.31); I = 84%; p < 0.001]. Patients treated with PET had more favorable outcomes in terms of overall survival [HR (95% CI): 1.24 (1.06, 1.46); I = 70%; p = 0.008] and less favorable outcomes in breast cancer-specific survival [HR (95% CI): 1.13 (0.98, 1.31); I = 41%; p = 0.10]. The risk of publication bias was assessed to be high in reporting local recurrence rates and low in reporting distant recurrence rates.

Conclusion: PET alone is inferior to surgery in the treatment of operable invasive breast cancer. However, it may be acceptable to postpone curative breast cancer surgery without risk of progression for 1.1 years or longer.