Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis

Daniel Reinhorn; Raz Mutai; Rinat Yerushalmi; Assaf Moore; Eitan Amir; Hadar Goldvaser

doi:10.1016/j.breast.2021.05.003

Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis

Breast. 2021 Aug:58:173-181. doi: 10.1016/j.breast.2021.05.003.

Authors

Daniel Reinhorn¹, Raz Mutai¹, Rinat Yerushalmi², Assaf Moore², Eitan Amir³, Hadar Goldvaser⁴

Affiliations

¹ Institute of Oncology, Rabin Medical Center, Petah- Tikva, Israel.
² Institute of Oncology, Rabin Medical Center, Petah- Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
³ Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
⁴ Oncology Institute, Shaare Zedek Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University, Jerusalem, Israel. Electronic address: hadargo@szmc.org.il.

Abstract

Background: Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).

Methods: RCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.

Results: Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14-0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65-1.43), triple negative (HR 1.4, 95% CI 0.50-3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68-1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62) and in visceral disease (HR = 1.02, 95% CI 0.77-1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.

Conclusions: LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.

Keywords: Breast cancer; Locoregional treatment; Surgery; Survival; de novo metastatic.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Breast Neoplasms* / therapy
Female
Humans
Proportional Hazards Models
Radiotherapy, Adjuvant
Survival Rate