Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for A Cost-Effective and Dynamic Biomarker.

Giacomo Pelizzari,Camilla Lisanti,Debora Basile,Silvia Zago,Gianpiero Fasola,Valentina Fanotto,Maria Grazia Vitale,Marika Cinausero,Fabio Puglisi,Serena Barban,Mauro Mansutti,Marta Bonotto,Lorenzo Gerratana,Francesco Curcio,Alessandro Marco Minisini,Lucia Bortot,Michele Bartoletti

doi:10.3390/cancers11091243

Abstract

Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40–5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16–5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00–7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

Highlights

Breast cancer (BC) is the most common cancer among women and the second leading cause of cancer-related death [1]
A consecutive series of 392 women with metastatic breast cancer (MBC) were included in the analysis, 219 with a plasmatic
At MBC diagnosis, nearly half of the patients presented with a single metastatic site, and about 20% had three or more localizations

Summary

Introduction

Breast cancer (BC) is the most common cancer among women and the second leading cause of cancer-related death [1]. Despite new treatments and improved standard of care, metastatic breast cancer (MBC) remains an incurable disease with a median survival of about 34 months, even if it varies significantly among and within the subgroups [5]. Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40–5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16–5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies

Methods

Results

Discussion

Conclusion