Proinflammatory circulating markers: new players for evaluating asymptomatic acute cardiovascular toxicity in breast cancer treatment

Abstract

Purpose

This study aimed to evaluate markers of cardiac damage (total CK, CKMB and CRP), inflammatory markers (free iron, homocysteine and TNF-α) as well as lipidogram in breast cancer patients undergoing acute cycles of doxorubicin (DOX), paclitaxel (PTX) or trastuzumab (TZ) and to verify if there is an association between these markers and the toxicity of the chemotherapeutic treatment. Methods: Included in the study were 120 breast cancer patients and 50 healthy controls. All analyzes were performed on automated systems. For the statistical analysis, each group was compared with the controls according to their normality by Student's t-test and Mann-Whitney test. Results: Our results showed that DOX treatment led to increased hsCRP (4.80 ± 1.23 mg/dL, p = 0.0005), triglycerides (187.6 ± 25.06, p = 0.0231), TNF-α (42.31 ± 17.96 pg/mL, p = 0.01) and Fe levels (138.8 ± 18.6 μg/dL, p = 0.0193). In the meantime, PTX induced changes in CK-MB (8.78 ± 4.2 U/L, p = 0.0361), hsCRP (7.12 ± 1.87 mg/dL, p = 0.0006), cholesterol (201.7 ± 19.54, p = 0.05), triglycerides (201.7 ± 19.54, p = 0.0277), TNF-α (38.27 ± 9.12 pg/mL, p = 0.023), homocysteine (10.95 ± 0, 86 μmol/L, p = 0.005), and free iron (113 ± 18 6 μg/dL, p = 0.045) while TZ augmented CK-MB (6.9 ± 1.97 U/L, p < 0.00), hsPCR (3.12 ± 0.68 mg/dL, p = 0.095), cholesterol (218.3 ± 16.79, p = 0.0317), triglycerides (218.3 ± 16.79, p = 0.0127), TNF-α (89.6 ± 12.11, p = 0.032), homocysteine (9.95 ± 1.15 μmol/L, p = 0.0396), free iron (120.5 ± 4.64 μg/dl, p = 0.0058) as well. Conclusions: Our data demonstrated the existence of a proinflammatory net triggered by breast cancer chemotherapy that could increase cardiomyocytes permeability and allow the leakage of circulating proteins as CK-MB and induce the production of hsCRP.

Keywords:

• breast cancer
• chemotherapy
• proinflammatory markers
• cardiac toxicity

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Funding

This research was granted by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant number 444830-2014/6 awarded by Dr. Carolina Panis.

Notes on contributors

P. L. Micheletti

Pamela Lonardoni Micheletti is biologist and Ph.D in Experimental Pathology. Her work is focused on understanding breast cancer biology and the mechanisms of toxicity triggered by chemotherapy.

J. Carla-da-Silva

Janaína Carla da Silva is a Master student in Sciences Applied to Health. Her research aims to understand how inflammatory mediators and environmental risk factors can affect breast cancer aggressiveness.

T. B. Scandolara

Thalita Basso Scandolara is a Ph.D student in Genetics. She is developing a research to investigate putative genetic mutations that can correlate to breast cancer aggressiveness and chemoresistance.

R. Kern

Rodrigo Kern is a Master student in Sciences Applied to Health. His work is focused on understand how the expression of some immune system molecules in breast tumors are related to the clinical behavior of breast cancer.

V. D. Alves

Vinicius Dias Alves is a medical student and support the research staff of the Laboratory of Tumor Biology, Unioste, Brazil.

J. Malanowski

Jessica Malanowski is a medical student and support the research staff of the Laboratory of Tumor Biology, Unioste, Brazil.

V. J. Victorino

Vanessa Jacob Victorino is Ph.D in Sciences and works in the field of tumor molecular biology.

A. C. S. A. Herrera

Ana Cristina Herrera is an oncological surgeon and support the research developed by the Laboratory of Tumor Biology, Unioste, Brazil.

D. Rech

Daniel Rech is an oncological surgeon and support the research developed by the Laboratory of Tumor Biology, Unioste, Brazil.

J. A. O. Souza

Janoário Athanazio de Souza is an oncological surgeon and support the research developed by the Laboratory of Tumor Biology, Unioste, Brazil.

A. N. C. Simão

Andrea Name Colado Simão is Ph.D in Sciences and Medicine, and works on the search of biomarkers in immune-related diseases.

C. Panis

Carolina Panis is Ph.D in Experimental Pathology by the State University of Londrina and has a post-doctoral fellow in Oncology in the National Cancer Institute (INCA, Brazil). Scientist and adjunct professor of Immunology and Tumor Biology in the State University of West Paraná, Her work is focused on the role of inflammatory mediators and redox signaling in breast biology.

I. Dichi

Isaias Dichi is a clinician and researcher in the field of nutrition. He has developed his research in the field of metabolic syndrome, inflammation and oxidative stress biomarkers in pathology.