Improving systemic breast cancer therapy: time to look beyond the primary tumour?

AIM: Intra and inter tumour heterogeneity is a known feature in cancer because tumour cells undergo changes at genetic and epigenetic level as they spread from their primary tumour site. Adjuvant treatment protocols in breast cancer are currently based on the biological characteristics of the primary tumour, which in most cases has been removed surgically. Considering tumour heterogeneity in metastases we examined the present status of knowledge regarding measurable differences in tumour profiling between the primary breast tumour and its synchronous axillary lymph node metastases (ALNM) and if so whether adjuvant therapy directed towards the tumour characteristics of the ALNM instead of those of the primary tumour is more effective. METHODS: We performed a literature search in Pubmed with the following MeSH headings: HUMAN and BREAST NEOPLASMS and RECEPTORS and ErbB-2. RESULTS: A significant change in tumour features was seen in metachronous metastases. In contrast, a high concordance of biomarker expression was reported between a primary breast tumour and its synchronous ALNM. CONCLUSION: Tumour heterogeneity is a challenge for targeted therapy. A poor response can be explained by the diversity of tumour cells. The biological profile of synchronous ALNM measured by oestrogen (ER), progesterone (PR) and her-2-neu receptor status does not differ from the primary breast tumour and is not predictive of the tumour profile in metachronous metastasis. New techniques, such as profiling of circulating tumour cells or tumour behaviour in xenografts, are promising in directing more effective adjuvant therapy.