Genetic Variants and Tumor Immune Microenvironment: Clues for Targeted Therapies in Inflammatory Breast Cancer (IBC).

International Journal of Molecular Sciences
Yulan GongSandra V Fernandez


To better understand the etiology of inflammatory breast cancer (IBC) and identify potential therapies, we studied genomic alterations in IBC patients. Targeted, next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) (n = 33) and paired DNA from tumor tissues (n = 29) from 32 IBC patients. We confirmed complementarity between cfDNA and tumor tissue genetic profiles. We found a high incidence of germline variants in IBC patients that could be associated with an increased risk of developing the disease. Furthermore, 31% of IBC patients showed deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We also characterized the tumor-infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1, and PD-L1) through immunohistochemistry (IHC) staining. In 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs, making them sensitive to PD-1/PD-L1 blocking therapies. Our results provide a rationale for considering PARP inhibitors and PD-1/PDL1 blocking immunotherapy in qualifying IBC patients.


Apr 20, 2004·Cancer Causes & Control : CCC·Phyllis A WingoPaul Gargiullo
Jun 1, 2006·Breast Disease·William F AndersonPaul H Levine
Sep 17, 2009·Journal of the National Cancer Institute·Karen Rowan
Mar 2, 2010·Breast Cancer Research and Treatment·Marijke WasielewskiMieke Schutte
Jun 22, 2010·Cancer·François BertucciPatrice Viens
Jul 7, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S DawoodM Cristofanilli
Jul 20, 2010·Immunological Reviews·Loise M FranciscoArlene H Sharpe
Sep 28, 2010·Nature Structural & Molecular Biology·Rémi BuissonJean-Yves Masson
Oct 21, 2010·CA: a Cancer Journal for Clinicians·Fredika M RobertsonMassimo Cristofanilli
Sep 29, 2011·Cancer·Gad RennertOfra Barnett-Griness
Aug 30, 2013·Science Translational Medicine·Stefani SprangerThomas F Gajewski
Dec 5, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F BertucciS J Van Laere
Jul 8, 2014·The Breast : Official Journal of the European Society of Mastology·François BertucciSteven Van Laere
Feb 20, 2015·Molecular Cancer Therapeutics·Sandip Pravin Patel, Razelle Kurzrock
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Jan 4, 2017·Journal of the National Comprehensive Cancer Network : JNCCN·Mary B DalySusan Darlow
Feb 9, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shiping JiaoMien-Chie Hung
Jun 6, 2017·The New England Journal of Medicine·Mark RobsonPierfranco Conte
Jul 26, 2017·Nature Reviews. Clinical Oncology·Wolf H FridmanGuido Kroemer
Apr 29, 2018·Nature Reviews. Cancer·Bora LimNaoto T Ueno
Jul 15, 2018·The Surgical Clinics of North America·Arjun MentaBora Lim
Jul 31, 2018·Nature Reviews. Immunology·Jannie BorstWolfgang Kastenmüller
Aug 16, 2018·The New England Journal of Medicine·Jennifer K LittonJoanne L Blum
Oct 6, 2018·European Journal of Breast Health·Burcu ÇakarRuchan Uslu
Apr 2, 2019·Cancer·Huma Q RanaBeth A Overmoyer
Oct 22, 2019·Gynecologic Oncology·Jennifer Taylor VenerisPanagiotis A Konstantinopoulos
Feb 23, 2020·International Journal of Molecular Sciences·Jennifer S WinnSandra V Fernandez
Dec 4, 2020·Breast Cancer Research : BCR·Sandra V FernandezKerry S Campbell
Jan 21, 2021·The New England Journal of Medicine·UNKNOWN Breast Cancer Association ConsortiumDouglas F Easton

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