Current issue
About the Journal
Scientific Council
Editorial Board
Regulatory and archival policy
Code of publishing ethics
Publisher
Information about the processing of personal data in relation to cookies and newsletter subscription
Archive
For Authors
For Reviewers
Contact
Reviewers
Annals reviewers in 2023
Annals reviewers in 2022
Annals reviewers in 2021
Annals reviewers in 2020
Annals reviewers in 2019
Annals reviewers in 2018
Annals reviewers in 2017
Annals reviewers in 2016
Annals reviewers in 2015
Annals reviewers in 2014
Annals reviewers in 2013
Annals reviewers in 2012
Links
Sklep Wydawnictwa SUM
Biblioteka Główna SUM
Śląski Uniwersytet Medyczny w Katowicach
Privacy policy
Accessibility statement
Reviewers
Annals reviewers in 2023
Annals reviewers in 2022
Annals reviewers in 2021
Annals reviewers in 2020
Annals reviewers in 2019
Annals reviewers in 2018
Annals reviewers in 2017
Annals reviewers in 2016
Annals reviewers in 2015
Annals reviewers in 2014
Annals reviewers in 2013
Annals reviewers in 2012
Serum levels of VEGF-A, sVEGFR-2 and galectin-3 do not correlate with clinical stage, tumor size,
or effectiveness of perioperative chemotherapy in patients with non-metastatic breast cancer
1
Klinika Chorób Wewnętrznych i Chemioterapii Onkologicznej, Samodzielny Publiczny Szpital Kliniczny im. A. Mielęckiego, Śląski Uniwersytet Medyczny w Katowicach
2
Zakład Promocji Zdrowia i Leczenia Otyłości, Wydział Nauk Medycznych w Katowicach, Śląski Uniwersytet Medyczny w Katowicach
3
Katedra i Zakład Biochemii, Wydział Nauk Medycznych w Katowicach, Śląski Uniwersytet Medyczny w Katowicach
Corresponding author
Iga Grochoła-Małecka
Klinika Chorób Wewnętrznych i Chemioterapii Onkologicznej, Samodzielny Publiczny Szpital Kliniczny im. A. Mielęckiego, Śląski Uniwersytet Medyczny w Katowicach, ul. Reymonta 8, 40-027 Katowice
Klinika Chorób Wewnętrznych i Chemioterapii Onkologicznej, Samodzielny Publiczny Szpital Kliniczny im. A. Mielęckiego, Śląski Uniwersytet Medyczny w Katowicach, ul. Reymonta 8, 40-027 Katowice
Ann. Acad. Med. Siles. 2022;76:96-105
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Tumor angiogenesis is regulated by numerous cytokines and growth factors, with vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 2 (sVEGFR-2), and galectin-3, playing a significant role in the process. There are conflicting data concerning changes in serum VEGF, sVEGFR-2 and galectin-3 levels in breast cancer (BC) patients during the course of the disease and chemotherapy (CTH). This study aimed to assess the serum levels of VEGF-A, sVEGFR-2, and galectin-3 in women starting adjuvant and neoadjuvant therapy for BC, and their changes during the treatment.
Material and methods:
This single-center study enrolled 98 women with non-metastatic BC, including 56 who started adjuvant therapy and 42 preoperative (neoadjuvant/induction) CTH. The serum levels of VEGF-A, sVEGFR-2, and galectin-3 were assessed at the beginning of CTH and after 2 subsequent months.
Results:
There were no significant differences in the serum levels of VEGF-A, sVEGFR-2, and galectin-3 between patients starting adjuvant and preoperative therapy. In addition, there was no correlation between the serum levels and the clinical stage of BC. During CTH, a significant increase in VEGF-A, sVEGFR-2, and galectin-3 was noted, however, without a predictive significance for obtaining complete pathological response (pCR) both for the initial levels and changes in the serum levels.
Conclusions:
The serum levels of VEGF-A, sVEGFR-2, and galectin-3 do not correlate with the clinical stage or tumor size in patients with non-metastatic BC. The baseline levels of VEGF-A, sVEGFR-2 and galectin-3, and the observed increase in the serum levels of VEGF-A and sVEGFR-2 during CTH do not predict its efficacy.
Tumor angiogenesis is regulated by numerous cytokines and growth factors, with vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 2 (sVEGFR-2), and galectin-3, playing a significant role in the process. There are conflicting data concerning changes in serum VEGF, sVEGFR-2 and galectin-3 levels in breast cancer (BC) patients during the course of the disease and chemotherapy (CTH). This study aimed to assess the serum levels of VEGF-A, sVEGFR-2, and galectin-3 in women starting adjuvant and neoadjuvant therapy for BC, and their changes during the treatment.
Material and methods:
This single-center study enrolled 98 women with non-metastatic BC, including 56 who started adjuvant therapy and 42 preoperative (neoadjuvant/induction) CTH. The serum levels of VEGF-A, sVEGFR-2, and galectin-3 were assessed at the beginning of CTH and after 2 subsequent months.
Results:
There were no significant differences in the serum levels of VEGF-A, sVEGFR-2, and galectin-3 between patients starting adjuvant and preoperative therapy. In addition, there was no correlation between the serum levels and the clinical stage of BC. During CTH, a significant increase in VEGF-A, sVEGFR-2, and galectin-3 was noted, however, without a predictive significance for obtaining complete pathological response (pCR) both for the initial levels and changes in the serum levels.
Conclusions:
The serum levels of VEGF-A, sVEGFR-2, and galectin-3 do not correlate with the clinical stage or tumor size in patients with non-metastatic BC. The baseline levels of VEGF-A, sVEGFR-2 and galectin-3, and the observed increase in the serum levels of VEGF-A and sVEGFR-2 during CTH do not predict its efficacy.
FUNDING
This study was funded by the Medical University of Silesia, Katowice, Poland. Project No. KNW-2-K59/D/6/K, KNW-2-055/D/5/N.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES (37)
1.
Estimated age-standardized incidence and mortality rates (World) in 2020, World, both sexes, all ages (excl. NMSC) (bar chart). Global Cancer Observatory, 2020 [online] <https://gco.iarc.fr/today/onli...> [accessed on 27 September 2022].
2.
Weidner N., Semple J.P., Welch W.R., Folkman J. Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N. Engl. J. Med. 1991; 324(1): 1–8, doi: 10.1056/NEJM199101033240101.
3.
Rykala J., Przybylowska K., Majsterek I., Pasz-Walczak G., Sygut A., Dziki A. et al. Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables. Pathol. Oncol. Res. 2011; 17(4): 809–817, doi: 10.1007/s12253-011-9387-6.
4.
Gao S., Ma J.J., Lu C. Prognostic significance of VEGF-C immunohistochemical expression in breast cancer: a meta-analysis. Tumour Biol. 2014; 35(2): 1523–1529, doi: 10.1007/s13277-013-1211-3.
5.
Regenfuss D., Cursiefen C. Concept of angiogenic privilege. In: D.A. Dartt, J.C. Besharse, R. Dana (eds.). Encyclopedia of the eye. Vol. 1. Academic Press. Oxford 2010, pp. 334–338.
6.
Massena S., Christoffersson G., Vågesjö E., Seignez C., Gustafsson K., Binet F. et al. Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans. Blood 2015; 126(17): 2016–2026, doi: 10.1182/blood-2015-03-631572.
7.
Seetharam L., Gotoh N., Maru Y., Neufeld G., Yamaguchi S., Shibuya M. A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF. Oncogene 1995; 10(1): 135–147.
8.
Ning Q., Liu C., Hou L., Meng M., Zhang X., Luo M. et al. Vascular endothelial growth factor receptor-1 activation promotes migration and invasion of breast cancer cells through epithelial-mesenchymal transition. PLoS One 2013; 8(6): e65217, doi: 10.1371/journal.pone.0065217.
9.
Dhakal H.P, Naume B., Synnestvedt M., Borgen E., Kaaresen R., Schlichting E. et al. Expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2 in invasive breast carcinoma: prognostic significance and relationship with markers for aggressiveness. Histopathology 2012; 61(3): 350–364, doi: 10.1111/j.1365-2559.2012.04223.x.
10.
Arias-Pulido H., Chaher N., Gong Y., Qualls C., Vargas J., Royce M. Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer. BMC Cancer 2012; 12: 298, doi: 10.1186/1471-2407-12-298.
11.
Failla C., Carbo M., Morea V. Positive and negative regulation of angiogenesis by soluble vascular endothelial growth factor receptor-1. Int. J. Mol. Sci. 2018; 19(5): 1306, doi: 10.3390/ijms19051306.
12.
Stevens M., Oltean S. Modulation of receptor tyrosine kinase activity through alternative splicing of ligands and receptors in the VEGF-A/VEGFR axis. Cells 2019; 8(4): 288, doi: 10.3390/cells8040288.
13.
Autenshlyus A., Arkhipov S., Mikhailova E., Arkhipova V., Varaksin N. VEGF-R2 and TNF-R1 expression and cytokine production by samples of mammary adenocarcinomas and correlations with histopathological parameters of these malignant tumors. Int. J. Immunopathol. Pharmacol. 2018; 32: 2058738418787990, doi: 10.1177/2058738418787990.
14.
Zajkowska M., Lubowicka E., Fiedorowicz W., Szmitkowski M., Jamiołkowski J., Ławicki S. Human plasma levels of VEGF-A, VEGF-C, VEGF-D, their soluble receptor – VEGFR-2 and applicability of these parameters as tumor markers in the diagnostics of breast cancer. Pathol. Oncol. Res. 2019; 25(4): 1477–1486, doi: 10.1007/s12253-018-0527-0.
15.
Toi M., Bando H., Ogawa T., Muta M., Hornig C., Weich H.A. Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int. J. Cancer 2002; 98(1): 14–18, doi: 10.1002/ijc.10121.
16.
Thielemann A., Baszczuk A., Kopczyński Z., Kopczyński P., Grodecka-Gazdecka S. Clinical usefulness of assessing VEGF and soluble receptors sVEGFR-1 and sVEGFR-2 in women with breast cancer. Ann. Agric. Environ. Med. 2013; 20(2): 293–297.
17.
Yang R.Y., Rabinovich G.A., Liu F.T. Galectins: structure, function and therapeutic potential. Expert Rev. Mol. Med. 2008; 10: e17, doi: 10.1017/S1462399408000719.
18.
Menon R.P., Hughes R.C. Determinants in the N-terminal domains of galectin-3 for secretion by a novel pathway circumventing the endoplasmic reticulum-Golgi complex. Eur. J. Biochem. 1999; 264(2): 569–576, doi: 10.1046/j.1432-1327.1999.00671.x.
19.
Yu L.G. Circulating galectin-3 in the bloodstream: An emerging promoter of cancer metastasis. World J. Gastrointest. Oncol. 2010; 2(4): 177–180, doi: 10.4251/wjgo.v2.i4.177.
20.
Yamaki S., Fujii T., Yajima R., Hirakata T., Yamaguchi S., Fujisawa T. et al. Clinicopathological significance of decreased galectin-3 expression and the long-term prognosis in patients with breast cancer. Surg. Today 2013; 43(8): 901–905, doi: 10.1007/s00595-012-0378-3.
21.
Iurisci I., Tinari N., Natoli C., Angelucci D., Cianchetti E., Iacobelli S. Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clin. Cancer Res. 2000; 6(4): 1389–1393.
22.
Topcu T.O., Kavgaci H., Gunaldi M., Akyol M., Mentese A., Yaman S.O. et al. The clinical importance of serum galectin-3 levels in breast cancer patients with and without metastasis. J. Cancer Res. Ther. 2018; 14(10): S583–S586, doi: 10.4103/0973-1482.176425.
23.
Shafiq A., Moore J., Suleman A., Faiz S., Farooq O., Arshad A. et al. Elevated soluble galectin-3 as a marker of chemotherapy efficacy in breast cancer patients: A prospective study. Int. J. Breast Cancer 2020; 2020: 4824813, doi: 10.1155/2020/4824813.
24.
Giuliano A.E., Connolly J.L., Edge S.B., Mittendorf E.A., Rugo H.S., Solin L.J. et al. Breast cancer-major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J. Clin. 2017; 67(4): 290–303, doi: 10.3322/caac.21393.
25.
Singh K., Tantravahi U., Lomme M.M., Pasquariello T., Steinhoff M., Sung C.J. Updated 2013 College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guideline recommendations for human epidermal growth factor receptor 2 (HER2) fluorescent in situ hybridization (FISH) testing increase HER2 positive and HER2 equivocal breast cancer cases; retrospective study of HER2 FISH results of 836 invasive breast cancers. Breast Cancer Res. Treat. 2016; 157(3): 405–411, doi: 10.1007/s10549-016-3824-x.
26.
AJCC cancer staging manual. 8th ed. Amin B.A., Edge S.B., Greene F.L., Byrd D.R., Brookland R.K., Washington M.K. et al. (eds.). Springer. New York 2017, doi 10.1007/978-3-319-40618-3_48.
27.
Pinder S.E., Provenzano E., Earl H., Ellis I.O. Laboratory handling and histology reporting of breast specimens from patients who have received neoadjuvant chemotherapy. Histopathology 2007; 50(4): 409–417, doi: 10.1111/j.1365-2559.2006.02419.x.
28.
El Tarhouny S., Seefeld M., Fan A.X., Hahn S., Holzgreve W., Zhong X.Y. Comparison of serum VEGF and its soluble receptor sVEGFR1 with serum cell-free DNA in patients with breast tumor. Cytokine 2008; 44(1): 65–69, doi: 10.1016/j.cyto.2008.06.008.
29.
Hodorowicz-Zaniewska D., Kibil W., Małek A., Szpor J., Kulig J., Sztefko K. Evaluation of serum concentrations of vascular endothelial growth factor (VEGF) in breast cancer patients. Pol. J. Pathol. 2012; 63(4): 255–260, doi: 10.5114/pjp.2012.32773.
30.
Stathopoulos J., Armakolas A., Stathopoulos G.P., Gomatos I.P. Plasma VEGF levels in breast cancer patients with and without metastases. Oncol. Lett. 2010; 1(4): 739–741, doi: 10.3892/ol_00000129.
31.
Wang R.X., Chen S., Huang L., Zhou Y., Shao Z.M. Monitoring serum VEGF in neoadjuvant chemotherapy for patients with triple‐negative breast cancer: A new strategy for early prediction of treatment response and patient survival. Oncologist 2019; 24(6): 753–761, doi: 10.1634/theoncologist.2017-0602.
32.
Fürstenberger G., von Moos R., Lucas R., Thürlimann B., Senn H.J., Hamacher J. et al. Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer. Br. J. Cancer 2006; 94(4): 524–531, doi: 10.1038/sj.bjc.6602952.
33.
Winter M.C., Wilson C., Syddall S.P., Cross S.S., Evans A., Ingram C.E. et al. Neoadjuvant chemotherapy with or without zoledronic acid in early breast cancer–a randomized biomarker pilot study. Clin. Cancer Res. 2013; 19(10): 2755–2765, doi: 10.1158/1078-0432.CCR-12-3235.
34.
Zarychta E., Rhone P., Bielawski K., Michalska M., Rość D., Ruszkowska-Ciastek B. Anti-angiogenic efficacy in invasive breast carcinoma patients depends on clinicopathological determinants. Adv. Med. Sci. 2019; 64(2): 216–223, doi: 10.1016/j.advms.2019.02.001.
35.
Boutas I., Potiris A., Brenner W., Lebrecht A., Hasenburg A., Kalantaridou S. et al. The expression of galectin-3 in breast cancer and its association with chemoresistance: a systematic review of the literature. Arch. Gynecol. Obstet. 2019; 300(5): 1113–1120, doi: 10.1007/s00404-019-05292-9.
36.
Boutas I., Potiris A., Makrakis E., Messaropoulos P., Papaioannou G., Kalantaridou S. The expression of Galectin-3 in breast cancer and its association with metastatic disease: a systematic review of the literature. Mol. Biol. Rep. 2021; 48(1): 807–815, doi: 10.1007/s11033-020-06122-x.
37.
De Luliis F., Salerno G., Taglieri L., Lanza R., Cardelli P., Scarpa S. Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast cancer. Int. J. Biol. Markers 2017; 32(3): e333–e336, doi: 10.5301/ijbm.5000262.
Share
RELATED ARTICLE
| eISSN: | 1734-025X |
The Medical University of Silesia in Katowice, as the Operator of the annales.sum.edu.pl website, processes personal data collected when visiting the website. The function of obtaining information about Users and their behavior is carried out by voluntarily entered information in forms, saving cookies in end devices, as well as by collecting web server logs, which are in the possession of the website Operator. Data, including cookies, are used to provide services in accordance with the Privacy policy.
You can consent to the processing of data for these purposes, refuse consent or access more detailed information.
You can consent to the processing of data for these purposes, refuse consent or access more detailed information.
