26530965 Visualization

A 42 Age - year Age - old Age woman Sex presented Clinical_event with a right Biological_structure breast Biological_structure lump Sign_symptom , lower Biological_structure back Biological_structure pain Sign_symptom , loss Sign_symptom of Sign_symptom height Sign_symptom , marked kyphosis Sign_symptom and hepatomegaly Sign_symptom .
Core biopsies Diagnostic_procedure from the breast Biological_structure lump Biological_structure showed ductal Disease_disorder carcinoma Disease_disorder in situ (sample labelled P1.1; Supplementary Fig.1 and Supplementary Table 1).
An additional biopsy Diagnostic_procedure from an ipsilateral Biological_structure axillary Biological_structure lymph Biological_structure node Biological_structure (P1.2) revealed metastatic Detailed_description ductal Disease_disorder adenocarcinoma Disease_disorder (ER+ (8/8) and HER2+ (3+)).
Computed Diagnostic_procedure tomography Diagnostic_procedure scan revealed widespread Detailed_description metastatic Disease_disorder disease Disease_disorder in bones Biological_structure , pleura Biological_structure and liver Biological_structure (Supplementary Fig.2 and Supplementary Table 2).
The patient was started on treatment with trastuzumab Medication and taxane Medication - based Medication chemotherapy Medication , with a significant Detailed_description partial Detailed_description response Sign_symptom (Supplementary Fig.3).
After induction Detailed_description chemotherapy Medication , she was maintained on tamoxifen Medication and trastuzumab Medication .
After 19 Duration months Duration on treatment, she presented with seizures Sign_symptom and head Biological_structure computed Diagnostic_procedure tomography Diagnostic_procedure revealed a large metastasis Sign_symptom in the left Biological_structure frontal Biological_structure lobe Biological_structure (Supplementary Fig.4), which was resected Therapeutic_procedure (M2.1).
Therapy with tamoxifen Medication and trastuzumab Medication was continued and collection of plasma Diagnostic_procedure samples Diagnostic_procedure was initiated (samples T1–T9).
Four Date months Date after Date surgery, she had enlarging Detailed_description liver Biological_structure lesions Sign_symptom and a new metastatic Sign_symptom deposit Sign_symptom in the left Biological_structure ovary Biological_structure (Supplementary Fig.5).
Treatment was switched to a combination of lapatinib Medication and capecitabine Medication , resulting in stable Sign_symptom disease Sign_symptom for 12 Duration months Duration (Supplementary Fig.6).
General Sign_symptom deterioration Sign_symptom then occurred, with disease Sign_symptom progression Sign_symptom in the chest Biological_structure (new pulmonary Biological_structure nodules Sign_symptom , bilateral Detailed_description pleural Disease_disorder effusions Disease_disorder and posterior Biological_structure chest Biological_structure wall Biological_structure mass Sign_symptom , Supplementary Fig.7; Eastern Diagnostic_procedure Cooperative Diagnostic_procedure Oncology Diagnostic_procedure Group Diagnostic_procedure performance Diagnostic_procedure status Diagnostic_procedure 2–3).
Treatment Therapeutic_procedure was stopped and the patient died Outcome ∼4 months Date later Date .
Tumour samples were obtained at diagnosis from the primary breast site (P1.1) and an axillary lymph node (P1.2); after 19 months from the brain metastasis area (M2.1); and at autopsy after 3 years on treatment (from the primary breast site, and from metastatic deposits in the chest, liver, ovary and vertebrae, labelled P3.1 and M3.1–M3.4, respectively).
Serial plasma samples were obtained over the last 500 days of clinical follow-up (T1–T9).
Tumour and plasma samples collected and the clinical course are summarized in Fig.1a,b.