Individual characterisation of the metastatic capacity of human breast carcinoma

The clinical implications of understanding the invasive and metastatic proc livities of an individual patient's tumour are substantial because the choi ce of systemic therapy needs to be guided by the likelihood of occult metas tasis as well as by knowing when the metastases will become overt. Malignan t potential is dynamic, progressing throughout the natural history of a tum our. Required of tumours is the development of critical phenotypic attribut es: growth, angiogenesis, invasion and metastagenicity. Characterisation of the extent of tumour progression with regard to these major tumour phenoty pes should allow the fashioning of individual therapy for each patient. To examine the clinical parameters and molecularly characterise the metastatic proclivity we have been studying a series of regionally treated breast can cer patients who received no systemic therapy and have long follow-up. Clin ically we describe two parameters: metastagenicity the metastatic proclivit y of a tumour, and virulence - the rate at which these metastases appear. B oth attributes increase with tumour size and nodal involvement. However, wi thin each clinical group there is a cured population. even in those with ex tensive nodal involvement, underscoring the heterogeneity of breast cancers within each group and the need for further molecular characterisation. Usi ng biomarkers that characterise the malignant phenotype we have determined that there is progression in the phenotypic changes. Angiogenesis and loss of nm23 are earlier events than the loss of E-cadherin, or abnormalities in TP53, The strongest biomarkers of poor prognosis are p53 and E-cadherin, b ut even when both are abnormal 42% of node-negative patients are cured indi cating that other determinative steps need to occur before successful metas tases are established. Identification of these critical later events will f urther increase the efficacy of determining the malignant capacities of ind ividual tumours. (C) 2000 Elsevier Science Ltd. All rights reserved.