Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma.

PURPOSE To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.

[1]  N. Weidner,et al.  Intratumoral microvessel density and L53 protein: Correlation with metastasis in head‐and‐neck squamous‐cell carcinoma , 1993, International journal of cancer.

[2]  Giampietro Gasparini,et al.  Erratum: “Evaluating the Potential Usefulness of New Prognostic and Predictive Indicators in Node-Negative Breast Cancer Patients,” , 1993 .

[3]  M. Toi,et al.  Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma , 1993, International journal of cancer.

[4]  T. Imazawa,et al.  Antitumor effect of the angiogenesis inhibitor agm-1470 and its combination effect with tamoxifen in dmba induced mammary-tumors in rats. , 1993, International journal of oncology.

[5]  W Blumenfeld,et al.  Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. , 1993, The American journal of pathology.

[6]  U. Veronesi,et al.  p53 as an independent prognostic marker in lymph node-negative breast cancer patients. , 1993, Journal of the National Cancer Institute.

[7]  W. McGuire,et al.  Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. , 1993, Journal of the National Cancer Institute.

[8]  M. Lippman The development of biological therapies for breast cancer , 1993, Science.

[9]  A. Howell,et al.  Assessment of tumour vascularity as a prognostic factor in lymph node negative invasive breast cancer. , 1993, European journal of cancer.

[10]  D. Visscher,et al.  Prognostic significance of image morphometric microvessel enumeration in breast carcinoma. , 1993, Analytical and quantitative cytology and histology.

[11]  W. Dupont,et al.  Breast cancer angio-histogenesis: through a narrow window. , 1992, Journal of the National Cancer Institute.

[12]  F Pozza,et al.  Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. , 1992, Journal of the National Cancer Institute.

[13]  A. Harris,et al.  Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer , 1992, The Lancet.

[14]  T. Visakorpi,et al.  Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. , 1992, Journal of the National Cancer Institute.

[15]  A. Lee,et al.  Microvessel quantitation and prognosis in invasive breast carcinoma. , 1992, Human pathology.

[16]  I. Henderson Breast cancer therapy--the price of success. , 1992, The New England journal of medicine.

[17]  E. Kawasaki,et al.  Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. , 1992, Journal of the National Cancer Institute.

[18]  J. Monson,et al.  Is the relationship between angiogenesis and metastasis in breast cancer real? , 1992, Surgical oncology.

[19]  C. Osborne,et al.  Prognostic factors for breast cancer: have they met their promise? , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  P Boracchi,et al.  Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  M. Barbareschi,et al.  Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms , 1992, The Journal of pathology.

[22]  F. Rilke,et al.  Peritumoral lymphatic invasion in patients with node‐negative mammary duct carcinoma , 1992, Cancer.

[23]  R. Weinberg,et al.  Tumor suppressor genes. , 1991, Science.

[24]  L. Liotta,et al.  Tumor invasion and metastasis: an imbalance of positive and negative regulation. , 1991, Cancer research.

[25]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[26]  Yumay Chen,et al.  Genetic mechanisms of tumor suppression by the human p53 gene , 1990, Science.

[27]  D. Ingber,et al.  Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth , 1990, Nature.

[28]  O. Halevy,et al.  Different tumor-derived p53 mutants exhibit distinct biological activities. , 1990, Science.

[29]  A. Lee,et al.  Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  D. Mason,et al.  JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections. , 1990, Journal of clinical pathology.

[31]  W. McGuire,et al.  Cathepsin D and prognosis in breast cancer. , 1990, The New England journal of medicine.

[32]  J. Folkman What is the evidence that tumors are angiogenesis dependent? , 1990, Journal of the National Cancer Institute.

[33]  F. Collins,et al.  Mutations in the p53 gene occur in diverse human tumour types , 1989, Nature.

[34]  M. Pea,et al.  Immunocytochemical detection of progesterone receptor by monoclonal KD-68 antibody in operable breast cancer: correlations with biochemical assay, pathological features and cell proliferative rate. , 1989, European journal of cancer & clinical oncology.

[35]  D. Hanahan,et al.  Induction of angiogenesis during the transition from hyperplasia to neoplasia , 1989, Nature.

[36]  V. Devita Breast Cancer Therapy: Exercising All Our Options , 1989 .

[37]  C K Osborne,et al.  Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study. , 1989, The New England journal of medicine.

[38]  C. Redmond,et al.  A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. , 1989, The New England journal of medicine.

[39]  C. Redmond,et al.  A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. , 1989, The New England journal of medicine.

[40]  M. Zelen,et al.  Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. , 1989, The New England journal of medicine.

[41]  W. McGuire Adjuvant therapy of node-negative breast cancer: another point of view. , 1988, Journal of the National Cancer Institute.

[42]  R. Gray A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk , 1988 .

[43]  W. Warren,et al.  Neuroendocrine components of the bronchopulmonary tract: hyperplasias, dysplasias, and neoplasms. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[44]  S. Bennett,et al.  Log‐Logistic Regression Models for Survival Data , 1983 .

[45]  A. Luini,et al.  Comparing Radical Mastectomy with Quadrantectomy, Axillary Dissection, and Radiotherapy in Patients with Small Cancers of the Breast , 1981 .

[46]  D. Gospodarowicz,et al.  Production a corpus luteum angiogenic factor responsible for proliferation of capillaries and neovascularization of the corpus luteum. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[47]  B. Fisher,et al.  The pathology of invasive breast cancer A Syllabus Derived from Findings of the National Surgical Adjuvant Breast Project (Protocol No. 4) , 1975, Cancer.

[48]  G. Moore Chemotherapy in stage I breast cancer. , 1967, JAMA.