1. Chronological occurrence of PI3KCA mutations in breast cancer liver metastases after repeat partial liver resection
- Author
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Giulia Hardoin, Julie Vasseur, Aldrick Ruiz, Marc-Antoine Allard, Jean-François Morère, Jocelyne Hamelin, Mylène Sebagh, Nelly Bosselut, René Adam, Antoinette Lemoine, Raphaël Saffroy, Department of Surgery [Utrecht, Pays-Bas], University Medical Center [Utrecht], Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pathologie [Villejuif], Hôpital Paul Brousse, Physiopathogenèse et Traitement des Maladies du Foie [Villejuif], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncogénétique [Villejuif], Université Paris-Sud - Paris 11 (UP11), Département de Cancérologie [Villejuif], The Netherlands Organization for Scientific Research (NOW). Grant number: 017.009.053., Physiopathogénèse et Traitement des Maladies du Foie, Hôpital Paul Brousse-Université Paris-Saclay, and Bodescot, Myriam
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0301 basic medicine ,Cancer Research ,Time Factors ,medicine.medical_treatment ,Metastases ,medicine.disease_cause ,Gastroenterology ,0302 clinical medicine ,Circulating tumor cell ,Surgical oncology ,Recurrence ,Prevalence ,Medicine ,Breast ,Cancer ,Aged, 80 and over ,Mutation ,Liver Neoplasms ,Nuclear Proteins ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Oncology ,Liver ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,France ,Research Article ,Adult ,Reoperation ,medicine.medical_specialty ,Lineage (genetic) ,Evolution ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,lcsh:RC254-282 ,03 medical and health sciences ,Breast cancer ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Lineage ,Internal medicine ,Genetics ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Hepatectomy ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Aged ,PI3KCA ,business.industry ,medicine.disease ,030104 developmental biology ,business ,Transcription Factors - Abstract
International audience; BACKGROUND:Liver metastases of breast cancer are frequent and can recur even after "complete/R0" resection in combination with systemic and hormonal treatments. The aim of this study was to analyze throughout repeat hepatectomies for liver metastases the evolution of PI3KCA gene mutational status.METHODS:All liver metastases nodules (n = 70) from 19 women who underwent at least 2 liver resections were reexamined. DNA extraction from archived tumoral tissue was performed and the major 'hot spot' mutations in the helical and catalytic domains of PI3KCA have been analyzed using Massarray platform (Agena Bioscience) based on allelic discrimination PCR amplification followed by sensitive mass spectrometry detection.RESULTS:The two major somatic hot spot PI3KCA mutations were found in 27 (38.6%) nodules corresponding to 8 of the 19 patients (42%). The frequency of women whose breast cancer liver metastases (BCLM) carries PI3KCA mutations increased from the first to the third hepatectomy. Tumors carrying PI3KCA mutations are significantly larger and more frequently observed when resections were R0 compared to patients with no PI3KCA mutation.CONCLUSION:PI3KCA mutations are frequently observed in BCLM and persist along with the recurrence. Their identification in circulating tumor cells should become a useful biomarker in the routine practice of breast cancer management to prevent tumor recurrence and overcome the problems of intra- and inter-tumoral heterogeneity of the current biomarkers.
- Published
- 2019