The effects of standard anthracycline-based chemotherapy on soluble ICAM-1 and vascular endothelial growth factor levels in breast cancer.
OBJECTIVE
The circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular endothelial growth factor (VEGF) are elevated in women with breast cancer and associated with tumor progression and poor prognosis. This study examined the effects of anthracycline-based chemotherapy on plasma sICAM-1 and VEGF, as well as soluble P-selectin, von Willebrand factor, and interleukin-6 levels.


METHODS
Twenty-six women diagnosed with stage I-IIIA breast cancer (mean age, 48.4 +/- 10.4 years; range, 34-79 years) were studied before (week 1) and at weeks 2 and 3 of cycles 1 and 4 of chemotherapy.


RESULTS
The initial effect of chemotherapy was to reduce sICAM-1 levels; compared with pretreatment, sICAM-1 levels were decreased at week 2 of both cycles (P values < 0.01). sICAM-1 levels were elevated, however, at the start of cycle 4 as compared with pretreatment (P < 0.01). Chemotherapy led to an increase in sICAM-1 levels in node-positive but not node-negative patients (P < 0.01). VEGF levels were decreased at week 2 of cycle 4 (P = 0.001) and remained so at week 3. Similar to sICAM-1, VEGF levels were elevated at the start of cycle 4 as compared with pretreatment (P < 0.006). Soluble P-selectin levels decreased during week 2 of cycle 4 (P = 0.026). Neither interleukin-6 or von Willebrand factor were significantly changed in response to chemotherapy.


CONCLUSIONS
The findings support prior studies suggesting that sICAM-1 levels derive from sources other than endothelial cells. In addition, whereas the more immediate effect of chemotherapy is to reduce sICAM-1 and VEGF, continued treatment may lead to significant elevations.
Department of Psychiatry, University of California San Diego, San Diego, California 92103, USA. pmills@ucsd.edu
Paul J
PJ
Mills
Barbara
B
Parker
Vicky
V
Jones
Karen A
KA
Adler
Christy J
CJ
Perez
Sherella
S
Johnson
Mairav
M
Cohen-Zion
Matthew
M
Marler
Georgia R
GR
Sadler
Joel E
JE
Dimsdale
Sonia
S
Ancoli-Israel
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019007:P-Selectin / Q000096:biosynthesis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D014841:von Willebrand Factor / Q000096:biosynthesis
D018943:Anthracyclines; D015850:Interleukin-6; D019007:P-Selectin; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1