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Gong Y , Nagarathinam R , Arisi MF , Gerratana L , Winn JS , Slifker M , Pei J , Cai KQ , Hasse Z , Obeid E , Noriega J , Sebastiano C , Ross E , Alpaugh K , Cristofanilli M , Fernandez SV
Genetic Variants and Tumor Immune Microenvironment: Clues for Targeted Therapies in Inflammatory Breast Cancer (IBC)
Int J Mol Sci. 2021 Aug 19;22(16)
PMID: 34445631    PMCID: PMC8396191    URL: https://www.ncbi.nlm.nih.gov/pubmed/34445631
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Abstract
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.
Notes
1422-0067 Gong, Yulan Nagarathinam, Rajeswari Arisi, Maria F Gerratana, Lorenzo Orcid: 0000-0002-8313-4834 Winn, Jennifer S Slifker, Michael Pei, Jianming Cai, Kathy Q Hasse, Zachary Obeid, Elias Noriega, Julio Sebastiano, Christopher Ross, Eric Alpaugh, Katherine Cristofanilli, Massimo Fernandez, Sandra V Orcid: 0000-0002-5859-963x Journal Article Int J Mol Sci. 2021 Aug 19;22(16):8924. doi: 10.3390/ijms22168924.