A common method of testing new cancer drugs is to use human breast tumour cells that have been transplanted into mice. How this transplantation process and drug treatments affect the grafted cells is not known. In particular, we need to know if certain types of mutation within the tumour may survive the process of engraftment better than others, resulting in a transplanted tumour that has a different composition and different properties from the original human tumour. Dr. Peter Eirew's aim is to study in detail how the “landscape” of different gene mutations in the tumor evolves when tumour cells undergo transplantation and subsequent treatment with anti-cancer drugs. Dr. Eirew will sequence the entire DNA and RNA (a measure of the active genes in a cell) of breast cancer patients' tumours before and after transplantation into mice to see how the frequency of each mutation changes over time. Dr. Samuel Aparicio's group has already read the entire DNA sequence of human breast cancer — both the original tumour and a recurrence in a different part of the patient's body nine years later — and showed that the type and frequency of the mutations changed over time. In the second part of the study, he will sequence these human tumour cells before and after the drug treatment to determine the types of mutations that survive. This will set the stage for a follow-on clinical study to determine how closely the drug response of these human cells predict how tumours in patients respond to the same drugs. This study will be the first attempt to define how grafted breast cancer cells behave in mice and how this behaviour is affected by the choice of grafting methods and treatment with existing drugs. This information will be used to improve the methods that are currently used to test potential new cancer drugs, with the ultimate aim of bringing new breast cancer treatments into routine use more quickly than in the past. Knowing the types and combination of mutations that are present in a tumour and how this combination changes during treatment will be the key to developing new and more effective drugs. The study may also identify new mutations in breast tumours, which have the potential to answer more specific questions about how these cancers arise, progress and become resistant to treatment.