5724d0fac534367de5fc911729d36d12 265124.pdf 1cc39ffe47de40edfac48a5899abbfd212816e46 265124.pdf 42bbee9655a819f3737d29c814eaf17c8f0c046be712b81de3d10d8821d7ae60 265124.pdf Title: Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer Subject: Despite the improvement achieved by the introduction of HER2-targeted therapy, up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown a significant improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). In ER+ HER2+ patients, target therapies such as phosphoinositide-3-kinase (PI3K) pathway inhibition or cyclin-dependent kinases 4/6 blocking may be effective in controlling downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies. Multiple trials have explored these strategies with some promising results, and probably, in the next years conclusive results will succeed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents such as HER-2 therapy plus checkpoint inhibitors, or new vaccines approaches have been investigated in this setting, with promising but controversial results obtained to date. Keywords: breast cancer; HER2-positive; estrogen receptor positive; triple-positive; HER2-targeted therapy; immunotherapy Author: Angelica Ferrando-Díez, Eudald Felip, Anna Pous, Milana Bergamino Sirven and Mireia Margelí Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Jul 8 05:41:57 2022 CEST ModDate: Fri Jul 8 05:46:21 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 23 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 926547 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IEFSKB+VnURWPalladioL Type 1 Custom yes yes no 10 0 CZUYDL+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 RWRAGG+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 TBNYOU+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 VTBDVA+CMSY10 Type 1 Builtin yes yes no 72 0 GOCQIR+EURM10 Type 1 Builtin yes yes no 76 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes no 111 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-17 02:32:03 CEST RepresentationInformation: 265124.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-06-16 12:29:33 CEST Size: 926547 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 511 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: HER2-Targeted Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: HER2-Positive Disease Current Approaches Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: HER2-Positive Early Breast Cancer Current Approaches Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: De-Escalation Approaches in the Early Setting Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Escalation Approaches in HER2-Positive EBC Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: HER2-Positive Advanced Breast Cancer Current Approaches Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: HER2 Heterogeneity as an Opportunity to Select the Best Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: The Role of the Estrogen Receptor in HER2-Positive Tumors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Crosslink between HER2 and Estrogen Receptors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Efficacy of Anti-HER2 and Endocrine Therapy in ER+/HER2+ Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Future Combination/Ongoing Studies to Improve the Efficacy of Endocrine Anti-HER2 in ER+/HER2+ Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Tumor Immunity and Immunotherapy in HER2-Positive Breast Cancer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: Role of Tumor Immunity in HER2-Positive Breast Cancer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Trials Testing Combinations with Immune-Therapeutic Drugs in HER2-Positive Breast Cancer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer Author: Angelica Ferrando-Díez, Eudald Felip, Anna Pous, Milana Bergamino Sirven and Mireia Margelí Subject: Despite the improvement achieved by the introduction of HER2-targeted therapy, up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown a significant improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). In ER+ HER2+ patients, target therapies such as phosphoinositide-3-kinase (PI3K) pathway inhibition or cyclin-dependent kinases 4/6 blocking may be effective in controlling downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies. Multiple trials have explored these strategies with some promising results, and probably, in the next years conclusive results will succeed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents such as HER-2 therapy plus checkpoint inhibitors, or new vaccines approaches have been investigated in this setting, with promising but controversial results obtained to date. 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