Breast Cancer

The Role of VEGF in Breast Cancer Slide kit provided by ResearchVEGF.com, an online resource sponsored by Genentech BioOncology

Angiogenesis and VEGF in cancer

Angiogenesis and VEGF play an important role in tumor biology ,[object Object],[object Object],[object Object],[object Object],[object Object],References: 1. Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027. 2. Ferrara N. Endocr Rev. 2004;25:581-611.

Several critical mechanisms are involved in tumor growth ,[object Object],Reference: 1. Hanahan D, Weinberg RA. Cell. 2000;100:57-70. Reprinted from Hanahan D, Weinberg RA, “The Hallmarks of Cancer,” in Cell, 2000;100:57-70, with permission from Elsevier.

VEGF expression is an important factor in breast cancer ,[object Object],[object Object],[object Object],[object Object],References: 1. Schneider BP, Miller KD. J Clin Oncol . 2005;23:1782-1790. 2. Foekens JA, Peters HA, Grebenchtchikov N, et al. Cancer Res. 2001;61:5407-5414.

VEGF is a key mediator of breast tumor angiogenesis ,[object Object],[object Object],Reference: 1. Relf M, LeJeune S, Scott PA, et al. Cancer Res. 1997;57:963-969. Reprinted with permission from the American Association for Cancer Research. Relf M, LeJeune S, Scott PA, et al. Cancer Res. 1997;57:963-969.

VEGF is overexpressed in breast tumor tissue ,[object Object],Reference: 1. Yoshiji H, Gomez DE, Shibuya M, Thorgeirsson UP. Cancer Res. 1996;56:2013-2016. Reprinted with permission from the American Association for Cancer Research. Yoshiji H, Gomez DE, Shibuya M, Thorgeirsson UP. Cancer Res. 1996;56:2013-2016.

VEGF is significant throughout breast tumor development Reference: 1. Folkman J. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology . Vol 2. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005:2865-2882. ,[object Object],[object Object],Adapted from Folkman 2005.

VEGF expression is ubiquitous in multiple forms of breast cancer ,[object Object],[object Object],[object Object],[object Object],References: 1. Foekens JA, Peters HA, Grebenchtchikov N, et al. Cancer Res. 2001;61:5407-5414. 2. Gasparini G, Toi M, Gion M, et al. J Natl Cancer Inst. 1997;89:139-147. 3. Konecny GE, Meng YG, Untch M, et al. Clin Cancer Res. 2004;10:1706-1716. 4. Linderholm B, Grankvist K, Wilking N, et al. J Clin Oncol. 2000;18:1423-1431. 5. Gasparini G, Toi M, Miceli R, et al. Cancer J Sci Am. 1999;5:101-111. 6. Brown LF, Berse B, Jackman RW, et al. Hum Pathol. 1995;26:86-91. 7. Jacobs EJ, Feigelson HS, Bain EB, et al. Breast Cancer Res. 2006;8:R22. 8. Van der Auwera I, Van Laere SJ, Van Den Eynden GG, et al. Clin Cancer Res. 2004;10:7965-7971.

Effects of VEGF in breast cancer beyond angiogenesis

VEGF may be involved in autocrine signaling pathways ,[object Object],[object Object],[object Object],References: 1. Mercurio AM, Lipscomb EA, Bachelder RE. J Mammary Gland Biol Neoplasia. 2005;10:283-290. 2. Weigand M, Hantel P, Kreienberg R, Waltenberger J. Angiogenesis. 2005;8:197-204.

Prevalence of VEGF in breast cancer

VEGF is overexpressed in the majority of breast tumors Reprinted from Clin Cancer Res , Vol. 10, Konecny GE, Meng YG, Untch M, et al, 1706-1716, 2004, with permission from the American Association for Cancer Research. ,[object Object],Reference: 1. Konecny GE, Meng YG, Untch M, et al. Clin Cancer Res. 2004;10:1706-1716. 61% (340/554) 19% (7/37) 78% (432/554) 22% (8/37) Histology Invasive ductal Invasive lobular 73% (100/137) 55% (259/474) 80% (109/137) 72% (343/474) Hormone-receptor status Negative Positive 53% (155/290) 63% (196/310) 72% (210/290) 75% (233/310) Lymph nodes Negative Positive 55% (271/497) 77% (88/114) 71% (353/497) 88% (100/114) HER-2/ neu Negative Positive 59% (359/611) 74% (453/611) Overall Positive for VEGF 121-206 Positive for VEGF 165-206 Variable

VEGF and metastasis in breast cancer

VEGF and microvessel density are associated with increased metastasis in breast cancer ,[object Object],[object Object],References: 1. Weidner N, Semple JP, Welch WR, Folkman J. N Engl J Med. 1991;324:1-8. 2. Toi M, Inada K, Suzuki H, et al. Breast Cancer Res Treat. 1995;36:193-204. Weidner N, Semple JP, Welch WR, Folkman J. N Engl J Med. 1991;324:1-8, Copyright © 1991 Massachusetts Medical Society.

VEGF may be involved in breast cancer bone metastasis ,[object Object],[object Object],Reference: 1. Aldridge SE, Lennard TW, Williams JR, Birch MA. Br J Cancer. 2005;92:1531-1537. Adapted by permission from Macmillan Publishers Ltd: Br J Cancer. 2005;92:1531-1537. © 2005.

VEGF as a prognostic and predictive factor in breast cancer

VEGF is correlated with poor survival in breast cancer Gasparini G, Toi M, Gion M, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997;89(2):139-147. Adapted by permission of Oxford University Press. Reference: 1. Gasparini G, Toi M, Gion M, et al. J Natl Cancer Inst. 1997;89:139-147. ,[object Object],[object Object]

VEGF and microvessel density are associated with poor prognosis in breast cancer ,[object Object],Adapted from Toi 1995. Reproduced with permission from Breast Cancer Research and Treatment. Guidi AJ, Berry DA, Broadwater G, et al. Association of angiogenesis in lymph node metastases with outcome of breast cancer. J Natl Cancer Inst. 2000;92(6):486-492. Adapted by permission of Oxford University Press. References: 1. Toi M, Inada K, Suzuki H, Tominaga T. Breast Cancer Res Treat. 1995;36:193-204. 2. Guidi AJ, Schnitt SJ, Fischer L, et al. Cancer. 1997;80:1945-1953. 3. Guidi AJ, Berry DA, Broadwater G, et al. J Natl Cancer Inst. 2000;92:486-492. ,[object Object]

VEGF may predict response to systemic therapy ,[object Object],[object Object],[object Object],[object Object],References: 1. Foekens JA, Peters HA, Grebenchtchikov N, et al. Cancer Res. 2001;61:5407-5414. 2. Liang Y, Brekken RA, Hyder SM. Endocr Rel Cancer. 2006;13:905-919. 3. Hyder SM. Endocr Rel Cancer. 2006;13:667-687. Reprinted with permission from the American Association for Cancer Research. Foekens JA, Peters HA, Grebenchtchikov N, et al. Cancer Res. 2001;61:5407-5414.

VEGF and other common breast cancer tumor markers

VEGF, estrogen, and estrogen receptor interactions in breast cancer ,[object Object],[object Object],[object Object],[object Object],[object Object],References: 1. Buteau-Lozano H, Ancelin M, Lardeux B, et al. Cancer Res. 2002;62:4977-4984. 2. Linderholm B, Grankvist K, Wilking N, et al. J Clin Oncol. 2000;18:1423-1431. 3. Fu č kar D, Dekani ć A, Š tifter S, et al. Int J Surg Pathol. 2006;14:49-55.

VEGF and HER-2 in breast cancer: a positive association ,[object Object],[object Object],References: 1. Yen L, You XL, Al Moustafa AE, et al. Oncogene. 2000;19:3460-3469. 2. Konecny GE, Meng YG, Untch M, et al. Clin Cancer Res . 2004;10:1706-1716.

VEGF secretion: linked to BRCA-1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Reference: 1. Kawai H, Li H, Chun P, et al. Oncogene. 2002;21:7730-7739.

VEGF in breast cancer: summary ,[object Object],[object Object],[object Object],[object Object],[object Object],References: 1. Foekens JA, Peters HA, Grebenchtchikov N, et al. Cancer Res. 2001;61:5407-5414. 2. Gasparini G, Toi M, Gion M, et al. J Natl Cancer Inst. 1997;89:139-147. 3. Konecny GE, Meng YG, Untch M, et al. Clin Cancer Res. 2004;10:1706-1716. 4. Linderholm B, Grankvist K, Wilking N, et al. J Clin Oncol. 2000;18:1423-1431. 5. Folkman J. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. Vol 2. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005:2865-2882. 6. Weidner N, Semple JP, Welch WR, Folkman J. N Engl J Med. 1991;324:1-8. 7. Buteau-Lozano H, Ancelin M, Lardeux B, et al. Cancer Res. 2002;62:4977-4984. 8. Fu č kar D, Dekani ć A, Š tifter S, et al. Int J Surg Pathol. 2006;14:49-55. 9. Kawai H, Li H, Chun P, et al. Oncogene. 2002;21:7730-7739.

Breast Cancer

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