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Association of angiogenesis and poor prognosis in node‐positive patients receiving anthracycline‐based adjuvant chemotherapy

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Abstract

Tumoral angiogenesis has been described as associated with poor prognosis in breast cancer, particularly for node negative breast cancer. The purpose of this study was to evaluate the influence of angiogenesis in node‐positive breast cancer and particularly its potential impact on adjuvant chemotherapy.

Patients and methods: One hundred and thirty‐five node‐positive breast cancer patients who received anthracycline or derivative based adjuvant chemotherapy were selected from the data base of the Institut Paoli Calmettes. Angiogenesis was evaluated using CD31 antibody. Other prognosis variables studied were: hormonal status, tumor size, hormonal receptors, Elston and Ellis grade, and number of involved lymph nodes.

Results: In multivariate analysis, a high level of angiogenesis was independently associated with a diminution of survival (p=0.007), and of metastasis‐free survival (p=0.003). Other variables associated with poor survival were progesterone receptor status p=0.003) and Elston' grade p=0.003), and with metastasis‐free survival, progesterone receptor status (p=0.018).

Conclusion: Tumoral angiogenesis appears to be an independent prognostic factor for node‐positive breast cancer, when treated with adjuvant chemotherapy. Adjuvant strategies for patients with a high level of angiogenesis should be discussed.

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References

  1. Early Breast Cancer Trialists' Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 339(8784): 1–15, 1992

    Google Scholar 

  2. Early Breast Cancer Trialists' Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 339(8785): 71–85, 1992

    Google Scholar 

  3. Gasparini G, Pozza F, Harris AL: Evaluating the potential usefulness of new prognostic and predictive indicators in nodenegative breast cancer patients. J Natl Cancer Inst 85(15): 1206–1219, 1993

    Google Scholar 

  4. Perren TJ: c-erbB-2 oncogene as a prognostic marker in breast cancer. Br J Cancer 63: 328–332, 1991

    Google Scholar 

  5. Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M, Henderson IC: c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. New Engl J Med 330: 1260–1266, 1994

    Google Scholar 

  6. Kovach JS, Hartmann A, Blaszyk H, Cunningham J, Schaid D, Sommer SS: Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value. Proc Natl Acad Sci USA 93: 1093–1096, 1996

    Google Scholar 

  7. Elledge RM, Gray R, Mansour E, Yu Y, Clark GM, Ravdin P, Osborne CK, Gilchrist K, Davidson NE, Robert N, Tormey DC, Allred DC: Accumulation of p53 protein as a possible predictor of response to adjuvant combination chemotherapy with cyclophosphamide, methotrexate, fluorouracil, and prednisone for breast cancer. J Natl Cancer Inst 87(16): 1254–1256, 1995

    Google Scholar 

  8. Silvestrini R, Benini E, Veneroni S, Daidone MG, Tomasic G, Squicciarini P, Salvadori B: p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients. J Clin Oncol 14(5): 1604–1610, 1996

    Google Scholar 

  9. Gasparini G, Barbareschi M, Doglioni C, Dalla Palma P, Mauri FA, Boracchi P, Bevilacqua P, Caffo O, Morelli L, Verderio P, Pezzella F, Harris AL: Expression of bcl-2 protein predicts efficacy of adjuvant treatment in operable node-positive breast cancer. Clin Cancer Res 1: 189–198, 1995

    Google Scholar 

  10. Fidler IJ, Ellis LM: The implication of angiogenesis for the biology and therapy of cancer metastasis. Cell 79: 185–188, 1994

    Google Scholar 

  11. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27–31, 1995

    Google Scholar 

  12. Gasparini G, Bonoldi E, Viale G, Verderio P, Boracchi P, Panizzoni GA, Radealli U, Di Bacco A, Guglielmi RB, Bevilacqua P: Prognostic and predictive value of tumour angiogenesis in ovarian carcinomas. Int J Cancer 69: 205–211, 1996

    Google Scholar 

  13. Fontanini G, Vignati S, Lucchi M, Mussi A, Calcinai A, Boldrini L, Chiné S, Silvestri V, Angeletti CA, Basolo F, Bevilacqua G: Neoangiogenesis and p53 protein in lung cancer: Their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression. Br J Cancer 75(9): 1295–1301, 1997

    Google Scholar 

  14. Gasparini G, Harris AL: Clinical importance of the determination of tumor angiogenesis in breast carcinoma: Much more than a new prognostic tool. J Clin Oncol 13(3): 765–782, 1995

    Google Scholar 

  15. Folkman J: The influence of angiogenesis research onmanagement of patients with breast cancer. Breast Cancer Res Treat 36: 109–118, 1995

    Google Scholar 

  16. Barinaga M: Designing therapies that target tumor blood vessels. Science 275: 482–484, 1997

    Google Scholar 

  17. Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: Experience from a large study with long term follow-up. Histopathology 19: 403–410, 1991

    Google Scholar 

  18. Jacquemier JD, Charpin C, Martin PM: Etude immunohistochimique par anticorps monoclonal (H222SP gamma) des récepteurs oestrogéniques: Corrélation avec l' analyse biochimique par radioligand pour 115 carcinomas mammaires. Bull Cancer 73: 107–119, 1986

    Google Scholar 

  19. Jacquemier JD, Penault-Llorca FM, Bertucci F, Sun ZZ, Houvenaeghel GF, Geneix JA, Puig BD, Bardou VJH, Hassoun JA, Birnbaum D, Viens PJ: Angiogenesis as a prognostic marker in breast carcinoma with conventional adjuvant chemotherapy: A multiparametric and immunohistochemical analysis. J Pathol 184: 130–135, 1998

    Google Scholar 

  20. Vermeulen PB, Libura M, Libura J, O'Neill PJ, van Dam P, van Marck E, van Oosterom AT, Dirix LY: Influence of investigator experience and microscopic field size on microvessel density in node-negative breast carcinoma. Breast Cancer Res Treat 42: 165–172, 1997

    Google Scholar 

  21. Barbareschi M, Weidner N, Gasparini N, Morrelli L, Forti S, Eccher C, Fina P, Caffo O, Leonardi E, Mauri F, Bevilacqua P, Dalla Palma P: Microvessel density quantification in breast carcinomas. Appl Immunohistochem 3: 75–84, 1995

    Google Scholar 

  22. Kaplan EL, Meier P: Non parametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1971

    Google Scholar 

  23. Peto R, Peto J: Asymptomatically efficient rank invariant test procedures. J R. Stat Soc A 135: 185–198, 1972

    Google Scholar 

  24. Cox DR: Regression models and life table (with discussion). J R Stat Soc B 34: 187–220, 1972

    Google Scholar 

  25. Peters WP, Ross M, Vredenburgh JJ, Meisenberg B, Marks LB, Winer E, Kurtzberg J, Bast RC Jr, Jones R, Shpall E, Wu K, Rosner G, Gilbert C, Mathias B, Coniglio D, Petros W, Henderson IC, Norton L, Weiss RB, Budman DR, Hurd D: High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer. J Clin Oncol 11(6): 1132–1143, 1993

    Google Scholar 

  26. Gianni AM, Siena S, Bregni M, Di Nicola M, Orefice S, Cusumano F, Salvadori B, Luini A, Greco M, Zucali R, Rilke F, Zambetti M, Valagussa P, Bonadonna G: Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: Five-year results. J Clin Oncol 15(6): 2312–2321, 1997

    Google Scholar 

  27. Weidner N, Semple JP, Welch WR, Folkman J: Tumor angiogenesis and metastasis – Correlation in invasive breast carcinoma. N Engl J Med 324(1): 1–8, 1991

    Google Scholar 

  28. Van Hoef MEHM, Knox WF, Dhesi SS, Howell A, Schor AM: Assessment of tumour vascularity as a prognostic factor in lymph node negative invasive breast cancer. Eur J Cancer 29A(8): 1141–1145, 1993

    Google Scholar 

  29. Gasparini G, Weidner N, Bevilacqua P, Maluta S, Dalla Palma P, Caffo O, Barbareschi M, Boracchi P, Marubini E, Pozza F: Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol 12(3): 454–466, 1994

    Google Scholar 

  30. Heimann R, Ferguson D, Powers C, Recant WM, Weichselbaum RR, Hellman S: Angiogenesis as a predictor of longterm survival for patients with node-negative breast cancer. J Natl Cancer Inst 88(23): 1764–1769, 1996

    Google Scholar 

  31. Axelsson K, Ljung B-ME, Moore DH II, Thor AD, Chew KL, Edgerton SM, Smith HS, Mayall BH: Tumor angiogenesis as a prognostic assay for invasive ductal breast carcinoma. J Natl Cancer Inst 87(13): 997–1008, 1995

    Google Scholar 

  32. Toi M, Kashitani J, Tominaga T: Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer 55: 371–374, 1993

    Google Scholar 

  33. Horak ER, Leek R, Klenk N, Lejeune S, Smith K, Stuart N, Greenall M, Stepniewska K, Harris AL: Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 340: 1120–1124, 1992

    Google Scholar 

  34. Weidner N, Folkman J, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G: Tumor angiogenesis: A new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84(24): 1875–1887, 1992

    Google Scholar 

  35. Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanaïani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P, Gatti C, Suzuki H, Tominaga T: Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst 89(2): 139–147, 1997

    Google Scholar 

  36. Toi M, Inada K, Hoshina S, Suzuki H, Kondo S, Tominaga T: Vascular endothelial growth factor and platelet-derived endothelial cell growth factor are frequently coexpressed in highly vascularized human breast cancer. Clin Cancer Res 1: 961–964, 1995

    Google Scholar 

  37. Protopapa E, Delides GS, Révész L: Vascular density and the response of breast carcinomas to mastectomy and adjuvant chemotherapy. Eur J Cancer 29A(10): 1391–1393, 1993

    Google Scholar 

  38. Paulsen T, Aas T, Borresen A-L, Verhaug JE, Lonning PE, Akslen LA: Angiogenesis does not predict clinical response to doxorubicin monotherapy in patients with locally advanced breast cancer. Int J Cancer 74: 138–140, 1997

    Google Scholar 

  39. Gasparini G, Fox SB, Verderio P, Bonoldi E, Bevilacqua P, Boracchii P, Dante S, Marubini E, Harris AL: Determination of angiogenesis adds information to estrogen receptor status in predicting the efficacy of adjuvant tamoxifen in nodepositive breast cancer patients. Clin Cancer Res 2: 1191–1198, 1996

    Google Scholar 

  40. Fox SB, Leek RD, Bliss J, Mansi JL, Gusterson B, Gatter KC, Harris AL: Association of tumor angiogenesis with bone marrow micrometastases in breast cancer patients. J Natl Cancer Inst 89(14): 1044–1049, 1997

    Google Scholar 

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Viens, P., Jacquemier, J., Bardou, V. et al. Association of angiogenesis and poor prognosis in node‐positive patients receiving anthracycline‐based adjuvant chemotherapy. Breast Cancer Res Treat 54, 205–212 (1999). https://doi.org/10.1023/A:1006112927565

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