(A) Timeline of the patient’s clinical events and interventions.

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(A) Timeline of the patient’s clinical events and interventions. (A) Timeline of the patient’s clinical events and interventions. (B) H&E of ductal non-special type (NST) (I) and micropapillary (V) components of the primary mixed invasive breast cancer. Immunostaining: Oestrogen and progesterone receptors are positive in about 10% of the nuclei of ductal NST (II and III) and in 70% (VI) and 40% (VII) of micropapillary subtype respectively. HER2 immunostaining is intense and complete (score 3+) in both histotypes (IV, VIII). (C) H&E staining of cell block section of fine needle aspiration (FNA) of supraclavicular lymph node showing micropapillary (blue) and glandular structures (yellow). (D) ERBB2 gene amplification by FISH in breast cancer cells. Red dots indicate the ERBB2 gene probe, and green signals represent the CEP17 reference probe. Magnification: 100x. (E) ddPCR analysis of matched plasma and CSF-derived ctDNA prior to T-DM1 treatment. BC, breast cancer; BSC, best supportive care; CSF, cerebrospinal fluid; ctDNA, circulating tumour DNA; EC-P, Epi-doxorubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 q21 days for four cycles followed by paclitaxel 175 mg/m2 q21days for four cycles; FFPE, formalin fixed, paraffin embedded; FISH, fluorescence in situ hybridisation; HERLAP, HERceptin or LAPatinib trial; OFS, ovarian function suppression; PD, progressive disease; RT, radiation therapy; T-DM1, trastuzumab emtansine; CNV, copy number variation. Giulia Siravegna et al. ESMO Open 2017;2:e000253 Copyright © European Society for Medical Oncology. All rights reserved.