Fig. 1

Treatment response of a PDX established from a AME patient (T13). a Clinical history of patient T13 and PDX establishment from the breast and the axillary lymph node tumour samples. The patient presented a mammary breast lesion initially diagnosed as atypical papilloma. The patient relapsed and underwent partial mastectomy 18 months later. The breast lesion was a benign AME, characterized by a proliferation of myoepithelial cells p63+, CD10+ around epithelium-lined spaces in a lobulated, tubular and papillary pattern. This lesion was sequenced and the HRAS G12S mutation was identified. Six months later, the patient presented a growing breast nodule in the same area and an axillary lymph node and bilateral lung metastases. Core needle biopsy of the breast tumour revealed a malignant AME ER positive. A biopsy of a lung metastasis was sequenced and the HRAS G12S mutation was identified. The patient received 6 cycles of chemotherapy with paclitaxel and bevacizumab followed by AC (Adriamycin + Cyclophosphamide). Repeat CT scans of the thorax showed progression of the lung metastases during and after chemotherapy treatment. Total mastectomy with axillary lymph node dissection after 12 months of chemotherapy was performed. The breast primary tumour was multifocal and 25% of cancer cells were ER positive. One lymph node (LN) was metastatic with capsular effraction. Samples from the breast tumor and the LN metastasis carried the HRAS G12S mutation and were engrafted to generate HBCx-120 and HBCx-121 PDX models, respectively. b histology of patients’ breast tumour and lymph node metastasis and matched PDX HBCx-120 and HBCx-121. Scale is indicated by a black bar measuring 100 µm (first row) and 50 µm (second and third rows). The breast tumour and the matched PDX HBCx-120 were ER + (25%) and PR negative. c Tumour growth of HBCx-121 PDX in response to different chemotherapies (eribulin, AC and capecitabine) and to the combination of trametinib with. Statistical analysis of tumour growth inhibition based on relative tumour volume was performed with the Mann–Whitney test. d Western Blot analysis of treated tumours showing the phosphorylation status of AKT, MEK, p44/42 MAPK (ERK) and S6. Tumours were harvested after 3 weeks of treatment and three xenografts from each treatment group were analysed