New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy

Pestana, Rodrigo Mendonça Cardoso; Silvino, Júnea Paolucci Paiva; Oliveira, Angélica Navarro de; Soares, Cintia Esteves; Sabino, Adriano de Paula; Simões, Ricardo; Gomes, Karina Braga

doi:10.36660/abc.20230167

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Original Article • Arq. Bras. Cardiol. 120 (12) • Dec 2023 • https://doi.org/10.36660/abc.20230167 linkcopy

New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy.

Objective This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO).

Methods This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%.

Results The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group.

Conclusion GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Breast Neoplasms; Cardiovascular Diseases; Doxorubicin; Biomarkers

Central Illustration
: New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy

Variable	Breast Cancer (n=34)	Controls (n=34)	p-value
Age (years)	50.2 ± 11.3	46.9 ± 16.9	0.349
BMI (kg/m ² )	27.91 ± 5.9	26.5 ± 6.2	0.340
Diabetes mellitus, yes (n, %)	3 (8.8)	2 (5.8)	<0.001*
Arterial hypertension, yes (n, %)	11 (32.4)	9 (26.8)	0.008*
DOXO dose (mg/m ² )	380.6 [360.0 – 400.0]	-	-
LVEF (%)	66.97 ± 2.33	-	-
Histological diagnosis, n (%)
Invasive ductal carcinoma	30 (88.2)
Lobular carcinoma	3 (8.8)
Special types	1 (2.9)	-	-
Molecular type
HER2+	18 (52.9)
Luminal	12 (35.3)
Triple negative	4 (11.8)	-	-

Biomarkers	Luminal (12, 35.3%)	HER2+ (18; 52.9%)	Triple negative (4; 11.8%)	p-value
CXCL-16 (pg/mL)	1.35 [0.96 - 1.59]	1.52 [1.25 - 2.53]	1.38 [1.03 - 2.52]	0.370
FABP3 (pg/mL)	1.36 [1.15 - 12.89]	1.21 [0.92 - 1.80]	0.63 [0.09 - 15.26	0.444
FABP4 (pg/mL)	0.21 [0.06 - 0.67]	0.86 [0.14 - 1.32]	0.82 [0.10 - 17.05]	0.248
LIGHT (pg/mL)	0.06 [0.02 - 1.21]	0.86 [0.06 - 46.41]	0.42 [0.12 - 0.92]	0.203
GDF-15 (ng/mL)	11.38 [3.82 - 15.15]	14.75 [11.10 - 19.54]	24.79 [17.92 - 1899.90]	0.030 ^†
sCD14 (pg/mL)	3.387 [0.026 - 5.574]	4.098 [1.362 - 5.031]	0.021 [0.005 - 4.767]	0.398
ucMGP (ng/mL)	0.09 [0.05 -18.93]	0.15 [0.09 - 0.29]	7.97 [0.06 - 15.87]	0.957

Biomarkers	Low risk (n=15)	Intermediate risk (n=10)	High risk (n=9)	p-value
CXCL-16 (pg/mL)	1.34 [1.19 – 1.90]	1.40 [0.96 – 1.72]	2.32 [1.43 – 2.83]	0.101
FABP3 (pg/mL)	1.00 [0.59 – 1.27]	1.37 [1.14 – 12.21]	11.37 [1.06 – 19.54]	0.022 ^†
FABP4 (pg/mL)	0.15 [0.08 – 0.62]	1.18 [0.48 – 1.41]	0.84 [0.08 – 1.41]	0.096
LIGHT (pg/mL)	0.41 [0.06 – 35.08]	0.06 [0.02 – 0.55]	4.35 [0.16 – 25.33]	0.115
GDF-15 (ng/mL)	11.74 [1.72 – 15.66]	14.91 [11.82 – 19.75]	17.53 [11.82 – 24.02]	0.066
sCD14 (pg/mL)	5.18 [3.51 – 6.78]	0.28 [0.02 – 5.23]	2.24 [0.47 – 4.52]	0.080
ucMGP (ng/mL)	0.16 [0.09 – 14.07]	0.88 [0.05 – 14.05]	0.11 [0.06 – 0.36]	0.620

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[TFN1001] BMI: body mass index; DOXO: doxorubicin; LVEF: left ventricular ejection fraction. * Significant p-value <0.050.