Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Understanding metastatic breast cancer through an autopsy series (#71)

Margaret C Cummings 1 2 , Peter T Simpson 2 , Lynne Reid 2 , Janani Jayanthan 2 , Louise Marquart 3 , Peter O'Rourke 3 , Sunil R Lakhani 1 2
  1. Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  2. University of Queensland, UQ Centre for Clinical Research, Herston, Queensland , Australia
  3. Queensland Institute of Medical Research, Herston, Queensland, Australia

Patients who die of breast cancer almost always die of metastatic disease rather than of complications of the primary tumour. Understanding the biology of metastasis is therefore fundamental to treating these patients, although it has long been assumed that treatment of the secondary tumours should be determined by characteristics of the primary tumour.
Using material obtained from autopsies from a series of 204 patients who died of metastatic breast cancer and for whom treatment details are available, we have been able to learn about the natural history of metastatic breast cancer, particularly the heterogeneity of the disease, and its clonal and phenotypic evolution. We have evaluated clinicopathological variables associated with metastatic disease, including the nature of the primary tumour compared with tumours from different metastatic sites within individuals. With nearly 1,200 metastases available to study, we have analysed the distribution of disease, including the frequency of metastases at various sites, with lung, liver and bone being the most common, and an average of 5 - 6 metastatic sites per patient. Immunoprofiling for ER, PR, Her2, Ki67, c-kit, EGFR and p53 was performed on all patients for whom the primary breast cancer (57) was available. Relative stability of Her2 status was observed between the primary tumour and metastases at different sites, whereas ER and PR expression was more variable. Genomic analysis was undertaken on a subset of patients and identified DNA copy number aberrations that are consistently altered in all lesions of a case (primary and metastases), and alterations found in metastases only, providing evidence of clonal evolution during metastatic progression.
In summary, analysis of this extraordinarily rare and well characterised clinicopathological autopsy resource is providing substantial insight into the nature of metastatic spread of breast cancer and will be important for informing treatment decisions.