The Effects of Standard Anthracycline-Based Chemotherapy on Soluble ICAM-1 and Vascular Endothelial Growth Factor Levels in Breast Cancer

• Published in: Clinical cancer research 2004-08, Vol.10 (15), p.4998-5003
• Main Authors: Mills, Paul J, Parker, Barbara, Jones, Vicky, Adler, Karen A, Perez, Christy J, Johnson, Sherella, Cohen-Zion, Mairav, Marler, Matthew, Sadler, Georgia R, Dimsdale, Joel E, Ancoli-Israel, Sonia
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anthracyclines - therapeutic use; Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Disease Progression; Endothelium, Vascular - pathology; Female; Humans; Intercellular Adhesion Molecule-1 - biosynthesis; Interleukin-6 - biosynthesis; Interleukin-6 - metabolism; Lymphatic Metastasis; Medical sciences; Middle Aged; Neoplasm Metastasis; P-Selectin - biosynthesis; Pharmacology. Drug treatments; Prognosis; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Time Factors; Tumors; Vascular Endothelial Growth Factor A - biosynthesis; von Willebrand Factor - biosynthesis
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-0734-04

Purpose: 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. Experimental Design: 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.