  Citation: Galiandro, F.; Agnes, S.; Moschetta, G.; Orlandi, A.; Clarke, G.; Bria, E.; Franceschini, G.; Treglia, G.; Giovinazzo, F. Prognostic Factors in Patients with Breast Cancer Liver Metastases Undergoing Liver Resection: Systematic Review and Meta-Analysis. Cancers 2022, 14, 1691. https://doi.org/10.3390/ cancers14071691 Academic Editor: Adam E. Frampton Received: 3 February 2022 Accepted: 23 March 2022 Published: 26 March 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Systematic Review Prognostic Factors in Patients with Breast Cancer Liver Metastases Undergoing Liver Resection: Systematic Review and Meta-Analysis Federica Galiandro 1 , Salvatore Agnes 1 , Giovanni Moschetta 1 , Armando Orlandi 2 , George Clarke 3 , Emilio Bria 2 , Gianluca Franceschini 4 , Giorgio Treglia 5,6,7, * and Francesco Giovinazzo 1, * 1 General Surgery and Liver Transplantation Unit, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy; federica.galiandro@policlinicogemelli.it (F.G.); salvatore.agnes@policlinicogemelli.it (S.A.); dott.moschetta@gmail.com (G.M.) 2 Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy; armando.orlandi@policlinicogemelli.it (A.O.); emilio.bria@policlinicogemelli.it (E.B.) 3 Department of Liver Surgery, Queen Elizabeth Hospital, Birmingham B15 2GW, UK; george.clarke@uhb.nhs.uk 4 Breast Unit, Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy; gianluca.franceschini@policlinicogemelli.it 5 Academic Education, Research and Innovation Area, General Directorate, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland 6 Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland 7 Faculty of Biomedical Sciences, Università della Svizzera italiana, 6900 Lugano, Switzerland * Correspondence: giorgio.treglia@eoc.ch (G.T.); francesco.giovinazzo@policlinicogemelli.it (F.G.) Simple Summary: Robust predictive and prognostic tools are needed in the management of breast cancer liver metastases (BCLMs). Until now, surgery has not been the gold standard of treatment of patients with BCLMs. The present manuscript highlights several predictive factors related to the primary tumor and the BCLM that may help to identify candidates for surgery with favorable outcomes in a large cohort of patients. Abstract: Background: The role of surgical resection of liver metastases in patients with breast cancer liver metastasis (BCLM) remains controversial. A systematic review and meta-analysis of prognostic factors related to survival after BCLM resection was performed. Methods: An electronic search of relevant publications was performed. Pooled outcome measures were expressed as hazard ratios (HRs), including 95% confidence interval values (95% CIs), and calculated through a random-effects model. Heterogeneity was tested through the I 2 index. Results: Thirty-five publications reported analyses on prognostic factors and survival. A total of 2782 patients who underwent liver resection for BCLM were included. Positive axillary lymph nodes at breast cancer diagnosis were an unfavorable survival factor (HR 1.74, 95% CI 1.25 to 2.41, I 2 = 0%). Cumulative predictive factor HRs (multiple liver metastases, size of the metastases, short interval between primary tumor and onset of liver disease) related to the BCLM pattern were 1.32 (95% CI 1.17 to 1.48, I 2 = 71%) and 1.51 (95% CI 1.15 to 1.98, I 2 = 76%) for surgical and pathological features (resection margin and presence of extrahepatic disease), respectively. Conclusion: Resection of BCLM may provide a survival benefit for selected patients. For better long-term results, surgical selection should consider both primary tumor and BCLM features such as negative axillary lymph nodes at breast resection, a single hepatic lesion, a time longer than 24 months between breast and hepatic diagnosis, and a realizable R0 liver resection. However, the high heterogeneity among studies suggests the need for an RCT to validate the present findings. Keywords: breast cancer; liver metastases; hepatic resection; prognostic factors; meta-analysis Cancers 2022, 14, 1691. https://doi.org/10.3390/cancers14071691 https://www.mdpi.com/journal/cancers