Breast Cancer Research and Treatment

, Volume 66, Issue 1, pp 9–15

The effect of tamoxifen on breast tumour vascularity

  • L.P. Marson
  • K.M. Kurian
  • W.R. Miller
  • J.M. Dixon
Article

Abstract

As there is experimental evidence to suggest that tamoxifen may exert an anti-angiogenic effect, the present study was designed to investigate the effect of primary tamoxifen on breast tumour angiogenesis. Fifty seven patients with large operable primary breast cancers were treated with tamoxifen (20 mg daily) for between three and six months prior to definitive surgery. Clinical response to treatment was assessed by serial ultrasound measurements of tumour volume and a responding tumour was defined as one in which there was a greater than 25 % reduction in volume at the end of treatment. Patients underwent a wedge biopsy at diagnosis and definitive surgery on completion of tamoxifen, thus providing tumour sections before and after treatment. Microvessel counts (mvc) were performed following staining with the endothelial cell marker, antibody to Factor VIII, and changes in mvc were correlated with response.

Forty three of 57 patients had tumours that responded to tamoxifen. There was no difference in pre-treatment mvc between non-responding and responding tumours. Post-treatment mvc was significantly higher in non-responding than responding tumours. There was a significant reduction in mvc in responding tumours following treatment with tamoxifen, and a significant increase in mvc was detected in non-responding tumours. A significant correlation was demonstrated between percentage change in mvc and percentage reduction in tumour volume. This is the first study to demonstrate a reduction in breast cancer angiogenesis in tumours that have responded to primary tamoxifen in the clinical setting.

breast cancer angiogenesis microvessel counts tamoxifen 

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References

  1. 1.
    Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82: 4-6, 1990Google Scholar
  2. 2.
    Folkman J: Angiogenesis and breast cancer. J Clin Oncol 12: 441-443, 1994Google Scholar
  3. 3.
    Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353-364, 1996Google Scholar
  4. 4.
    Relf M, LeJeune S, Scott PAE, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL: Expression of the angiogenic factors vascular endothelial growth factor, acidic and basic fibroblast factor, tumor growth factor b-1, platelet-derived endothelial growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57: 963-969, 1997Google Scholar
  5. 5.
    Rastinejad F, Polverini PJ, Bouck NP: Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 56: 345-355, 1989Google Scholar
  6. 6.
    Abeloff MD, Lichter AS, Niederhuber JE, Pierce LJ, Aziz DC: Breast. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE (eds) Clinical Oncology. Churchill Livingstone, New York, 1995, pp 1617-1714Google Scholar
  7. 7.
    Sypridopoulos I, Sullivan AB, Kearney M, Isner JM, Losardo DW: Estrogen-receptor-mediated inhibition of human endothelial cell apoptosis. Circulation 95: 1505-1514, 1997Google Scholar
  8. 8.
    Gagliardi A, Taylor M, Hennig B, Collins DC: Antiestrogens inhibit endothelial cell growth. Proc A ACR 36: 1014, 1995Google Scholar
  9. 9.
    Lindner DJ, Borden EC: Effects of tamoxifen and interferon-b or the combination on tumor-induced angiogenesis. Int J Cancer 71: 456-461, 1997Google Scholar
  10. 10.
    Makris A, Powles TJ, Kakolyris S, Dowsett M, Ashley SE, Harris AL: Reduction in angiogenesis after neoadjuvant chemoendocrine therapy in patients with operable breast carcinoma. Cancer 85: 1996-2000, 1999Google Scholar
  11. 11.
    Anderson ED, Forrest AP, Hawkins RA, Anderson TJ, Leonard RC, Chetty U: Primary systemic therapy for operable breast cancer. Br J Cancer 63: 561-566, 1991Google Scholar
  12. 12.
    Vermeulen PB, Gasparini G, Fox SB, Toi M, Martin L, Mc-Culloch P, Pezzella F, Viale G, Weidner N, Harris AL, Dirix LY: Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria for evaluation. Eur J Cancer 32A: 2474-2484, 1996Google Scholar
  13. 13.
    Morales DE, McGowan KA, Grant DS, Maheshwari S, Bhartiya D, Cid MC, Kleinman HK, Schnaper HW: Estrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model. Circulation 91: 755-763, 1995Google Scholar
  14. 14.
    Jacobs TW, Siziopikou KP, Prioleau JE, Raza S, Baum JK, Hayes DF, Schnitt SJ: Do prognostic marker studies on core needle biopsy specimens of breast carcinoma accurately reflect the marker status of the tumour? Mod Pathol 11: 259-264, 1998Google Scholar
  15. 15.
    Marson L, Kurian K, Miller W, Dixon J: Reproducibility of microvessel counts in breast cancer specimens. Br J Cancer 81: 1088-1093, 1999Google Scholar
  16. 16.
    Hlatky L, Tsionou C, Hahnfeldt P, Coleman CN: Mammary fibroblasts may influence breast tumor angiogenesis via hypoxia-induced vascular endothelial growth factor upregulation and protein expression. Cancer Res 54(0008-5472):, 6083-6086, 1994Google Scholar
  17. 17.
    Cameron DA, Ritchie AA, Langdon SP, Anderson TJ, Miller WR: Tamoxifen induced apoptosis in ZR-75 breast cancer xenografts antedates tumour regression. Breast Cancer Res Treat 45: 99-107, 1997Google Scholar
  18. 18.
    Osborne CK, Wiebe VJ, McGuire WL, Ciocca DR, DeGregorio MW: Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients. J Clin Oncol 10: 304-310, 1992Google Scholar
  19. 19.
    Keen JC, Dixon JM, Miller EP, Cameron DA, Chetty U, Hanby A, Bellamy C, Miller WR: The expression of Ki-S1 and Bcl-2 and the response to primary tamoxifen therapy in elderly patients with breast cancer. Breast Cancer Res Treat 44: 123-133, 1997Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • L.P. Marson
    • 1
  • K.M. Kurian
    • 1
  • W.R. Miller
    • 1
  • J.M. Dixon
    • 1
  1. 1.Edinburgh Breast UnitWestern General HospitalEdinburgh, ScotlandUK

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