Index

A BRCA 1/2 mutations ABT-888 (Veliparib), 67 in triple-negative breast cancer, 68, 69 Alcohol consumption, 118, 119 BRCA mutation-associated metastatic breast Aldefuor assay, 35 cancer, 68 ALDH1A, 35 BRCA1 and BRCA2 mutations, 118, 122 ALDH1A1, 35, 36 BRCA1-assoicated breast cancer Allred scoring system, 14 (BABC), 108 American Cancer Society (ACS), 119 BRCA1 carrier, 38–40 Anastrozole, 120 BRCA1 , 154 Apocrine carcinoma, 4 BRCA1-related breast cancer, 107, 108 Apolipoprotein B mRNA-editing enzyme, clinical impact, 113 catalytic polypeptide-like 3G in vitro studies, 108, 109 (APOBEC3G), 145 in vivo studies, 110–112 Apoptosis, 85, 164 industry relationships, 113 Apoptosis , 42 innovation, 110, 112 Applied biosystems (ABI), 142 BRCA2 Carriers, 38–40 Aromatase inhibitors (AIs), 120, 121 BRCAPRO, 118 Artifcial intelligence, 178, 181 Breast and Ovarian Analysis of Disease AZA, 98 Incidence and Carrier Estimation AZD228 (Olaparib), 67 Algorithm (BOADICEA), 118 AZD2461, 67 Breast cancer in premenopausal women, 177 sporadic, survival in, 37, 38 B survival in Basal epithelial-cell-enriched gene cluster, 6 BRCA1 and BRCA2 carriers, 38–40 Basal-like breast cancer (BLBC), 68 factors, 43–45 Basal-like subtype breast cancer, 6, 7, 13, 14 markers, 40–43 Beta-catenin, 99 screening, 45 BHLHE22 gene, 134, 145 synopsis, treatment of Bilateral prophylactic salpingo-­ chemotherapy, 56, 57 oophorectomy, 66 endocrine therapy, 55, 56 BI-RADS ratings, 178 immunotherapy, 57–60 Blood tests, 179 radiotherapy, 55 Bouin’s solution fxation, 91 surgery, 54

© Springer Nature Switzerland AG 2021 187 J. Russo, The Future of Prevention and Treatment of Breast Cancer, https://doi.org/10.1007/978-3-030-72815-1 188 Index

Breast cancer genotypes Combined endocrine receptor (CER), 14 classifcation, 5 Computer-aided detection (CAD), 178 METABRIC classifcation, 8 Contralateral breast cancer (CBC), 39 molecular subtypes, 6–8 Copy number aberrations (CNAs), 8 normal cell subtype-based classifcation Copy number variants (CNVs), 8 system, 9, 10 Core needle biopsies (CNBs), 130 Breast Cancer Index, 19 CpG islands Breast cancer recurrence, 33, 34 of EMT, 80 factors, 43–45 CRISPR-Cas9 mutagenesis, 179 markers of, 34–37 CXCL12, 36 Breast Cancer Risk Assessment Tool (BCRAT/ CXCR4, 36 GAIL Model), 118 Cyclophosphamide–methotrexate–fuorouracil Breast cancer susceptibility gene1 (CMF), 56 (BRCA1), 107 Cytokeratin 5, 134 Breast Imaging Reporting and Data system Cytokeratin 5 and 6 (CK5/6), 7 (BI-RADS), 166–168 BSI-201 (Iniparib), 67 D DAC, 98 C Desmocollin (DSC3), 134, 143 Cancer Differentially methylated regions blood tests, 179 (DMRs), 150 health records, 181 Differentiated function, 164 lifestyle factors and risk, 177 Digital mammography, 167 mammographic screening, 178 DNA-methylation, 112 preventive strategy in hereditary breast DNA methylation inhibitors, 98 cancer, 181–182 DNA methyltransferase, 80 targeted drugs, 179–180 DNA methyltransferase inhibitor Cancer Genome Atlas database, 2 (DNMTi), 76, 108 Cancer survival DNA sequence analysis, 19 BRCA1 and BRCA2 carriers, 38–40 DNMTi, 83, 84, 92 factors, 43–45 Downregulated , 144 in sporadic breast cancer, 37, 38 Doxorubicin, 56 markers, 40–43 Ductal carcinoma, 15 screening, 45 Ductal tissue, 164 CancerSEEK, 169 cBioPortal, 134 CBX3, 149 E CD44+CD24-/lowLineage, 35 E-cadherin (CDH1) gene, 76, 91 Cell communication, menopausal breast, 143 E-cadherin staining, 3, 5 Chemo-preventive drugs, 120 Edwin Smith surgical papyrus, 129 Chemo-preventive strategies, 121, 122 Electronic health records (EHRs), 181 Chemotherapy (CT), 37 ELL-associated factor 2 (EAF2), 144 breast cancer, 56, 57 Endocrine therapy Chromatin condensation, 148, 149 breast cancer, 55, 56 Chromatin remodeling, 149, 153, 154 EpCAM, 91, 98 Chromobox homolog 3 (CBX3), 148 N-terminal EGF-like domain of, 93 Circulating tumor cells (CTCs), 21, 34 Epidermal growth factor receptor Circulating tumor DNA (ctDNA), 21 (EGFR), 7, 15 CLAUS, 118 Epigenetic changes Clinical trials, 121 CBX3, 149 c-Met, 41 chromatin condensation, 148 COBRA 1 gene, 150 chromatin remodeling, 149, 150, 152 Index 189

gene methylation, 152 downregulated genes, 144 HTN and EUN, 148, 149 pathway, 143 Epigenetic reprograming long noncoding RNA in GSP of epithelial mesenchymal transition, 78–91 menopausal breast, 141–143 triple-negative breast cancer, 96 parous vs. nulliparous women, 137, 138 Epithelial membrane antigen, 3 RNA processing pathway and Epithelial mesenchymal transition up-regulated genes, 139 (EMT), 3, 76 premenopausal breast changes after epigenetic reprograming, generalization frst FTP of, 97, 98 CD2 and CD3D for T cell activation, epigenetic reprogramming of, 78–91 134, 137 molecular interpretation, 91–96 GO terms, 131, 134 ERBB2 gene, 15 long-term changing and long-term ERBB2 overexpression cluster, 6 constant genes, 131 ERBB2+/HER2+, 6 parous differentially expressed ErbB3, 42 genes, 136 Estrogen plus progestogen therapy (EPT), 164 parous vs. nulliparous women, 131, 132 Estrogen receptor pathway, 143 pathway representing T cell signaling, Estrogen receptors (ER), 12–14, 19, 55 132, 135 Estrogen response elements (EREs), 13 premenopausal breast changes, post Euchromatin-rich nuclei (EUN), 148 full-term pregnancy, 136 Exemestane, 120 Genomic signature of breast cancer, 19, 20 Extracellular signal-regulated kinases Genomics, 180 (ERKs), 15 G protein-coupled receptor (GPCR), 36 EZH2, 96, 154 Grail study, 21 GSK3B, 150 Guadecitabine, 98, 113 F Fibrous stroma, 164, 166 Final grade (FG), 11 H First full-term pregnancy (FFTP), 120, 121 hCG levels, 153 Food and Drug Administration, 179 HDAC inhibitors, 80 Formalin-Fixed Paraffn-Embedded HDACi, 84, 92 (FFPE), 18 HER2/neu (c-erbB-2), 16 Frizzled family receptor 8 (FZD8), 144 HER2-positive disease, 57 Full-term pregnancy (FTP), 130–132, 146, Herceptin, 16 147, 153 Hereditary breast cancer Fulvestrant, 13 approaches, treatment of, 66 Future tests for screening, 168, 169 chemoprevention strategy, 65 prevention vs. treatment of, 70 susceptibility genes and possible target of G therapy, 69, 70 Gene methylation, 152 treatment, emerging modalities of, 67, 68 Genomic changes triple-negative breast cancer, BRCA 1/2 epigenetic changes mutations in, 68, 69 CBX3, 149 -rich nucleus (HTN), 148 chromatin condensation, 148 High power felds (HPF), 11 chromatin remodeling Histologic grade (HG), 10, 11 process, 149–151 Histone 3 dimethylated at lysine 9 gene methylation, 152 (H3K9me2), 148 HTN and EUN, 148 Histone deacetylase (HDAC), 76 postmenopausal breast Histone deacetylase inhibitor cell communication, 143 (HDACi), 76, 108 190 Index

Histone H3 methylation on lysine 27 Lipidomics, 180 (H3K27me3), 153 Liquid biopsies, 21, 169, 179 Histone lysine methylation, 154 Lobular carcinoma, 16 Histone methylation, 148 Local Alignment Search Tool (BLAST), 142 HLA-DPA1, 146 Long-term changing genes, 131, 133, 136, 144 Hormone prevention, 120 Luminal A-subtype breast cancers, 6, 8 Hormone Receptor Subtypes, 9 Luminal B-subtype breast cancers, 6, 7, 16, 17 Hormone therapy (HT), 164, 165 Lymphocytic infltration, 12 Human epidermal growth factor receptor 2 (HER2), 14–16 Human reference genome (hg 18), 150 M Hyperchromasia, 148 Malignancies, 34 MammaPrint, 18 Mammary gland involution, 145 I Mammary Prevention 3 (MAP.3), 120 Immunohistochemistry (IHC) tests, 16 Mammographic breast density, 118, 163, 164 Immunotherapy Mammographic screening, 178 breast cancer, 57–60 biological basis of breast density, 164, 166 Individual modifable risk factors, 119 BI-RADS, 166, 167 Iniparib, 67 evaluation, 168 Insulin-like growth factor (IGF-1), 139, hormones and breast density, 164 144, 177 risk of breast cancer, 163 Integrative Clusters (IntClust 1–10), 8 Volpara Algorithm, 168 Integrative Genomics Viewer (IGV), 150 Matrigel invasion assay, 81 Interchromatin granule clusters, 139 MCF10A, 78 Interleukin-6 (IL-6), 42 MCF10F cells, 78, 81, 153 International Breast Cancer Intervention Study Medullary carcinoma, 4 (IBIS), 118 Menopause, 164 International Breast Cancer Intervention Study Metabolomics, 180 II (IBIS-II), 120 Metformin, 121 Intraclass correlation coeffcient (ICC), 134 Methylcellulose matrix, 82 Intraepithelial neoplasia, 118 Micro chimeric cells, 146 Intrinsic Gene Subset, 6 Microbiomic data, 180 Invasive breast cancer, 2–5 Microinvasive carcinoma, 3, 5 Invasive lobular carcinomas (ILC), 4 Million Women Study, 164 Ipsilateral breast recurrence (IBR), 39 Mitogen-activated protein kinase (MAPK), 15 Mitotic grade (MG), 10–11 Molecular profling, breast cancer, 17, 18 J Molecular Taxonomy of Breast Cancer Juvenile (secretory) carcinoma, 4 International Consortium (METABRIC), 8 MS275, 80, 84, 86, 87, 89, 90, 94, 99, K 100, 108 Kaplan–Meier survival curve, 43, 134 Multivariate Alternative Transcript Splicing Ki-67 protein, 7, 17 Software (MATS), 140 Multivariate Cox hazard regression analysis, 43 L Myelodysplastic syndrome (MDS), 98 L3MBTL gene, 149 Landmarks, in history of breast cancer, 130 Lapatinib, 59 N Leukemia, 98 NanoString, 18 Lifestyle factors, 119 NEAT1 and NEAT2, 141 Index 191

Next-generation sequencing (NGS), 69 WNT/Notch signaling, 144 Non-insulin-dependent (type 2) diabetes, 121 Postmenopausal women, genomic signature Normal breast-like subtype, 6 cell communication, 143 Normal Cell Subtype-based classifcation PPP2CA (PP2A), 150 system, 9, 10 Premenopausal women Not otherwise specifed (NOS), 3 BHLHE22, 145 Notch signaling, 41 breast changes after frst FTP Notch1 expression, 41 CD2 and CD3D for T cell activation, Nuclear grade (NG), 10, 11 134, 137 Nuclear speckles, 139 GO terms, 131, 134 Nulliparity, 129 long-term changing and long-term Nuns, 129 constant genes, 131, 133 Nurses’ Health Study, 164 parous differentially expressed genes, 136 parous vs. nulliparous women, 131, 132 O pathway representing T cell signaling, Obesity, 177 132, 135 Omega-3 fatty acids (n-3), 122 chromatin remodeling, 145 Oncotype Dx, 17, 19 EAF2, 144 Ovarian function suppression (OFS), 56, 120 FZD8, 144 Ovariectomy, 120 genomic changes post full-term Oxytocin, 141 pregnancy, 136 immune system, 145 mRNA processing reactome, 147 P stromal , 146 , 100 transcriptomic profle, 146, 147 PAM50 assay, 18 Pre-mRNA splicing process, 139, 147 PARP inhibitors, 67 Present options, breast cancer prevention PARPi, 68 avoiding risk factors, 118 Pertuzumab, 16, 58 chemo-preventive strategies, 121, 122 Phosphoinositide 3-Kinase/Protein Kinase B clinical trials, 121 (PI3K/Akt) pathway, 15 hormone prevention, 120 PI3K/AKT/mTOR pathways, 150 lifestyle factors, 119 PI3K-Akt signaling, 140 mammographic breast density, 118 Plakoglobin, 34 reproductive factor, 120, 121 Platinum, 68 (PR), 12–14, 19, 55 Poly (ADP-ribose) polymerase 1 (PARP-1), 67 Prognostic markers Poly (ADP-ribosyl) ation, 67 ER and PR as biomarkers, 12–14 Polycomb group (PcG) protein, 149 estrogen receptors, 19 Postmenopausal breast, genomic signature HER2, 14–16 cell communication, 143 Ki-67, 17, 19 chromatin remodeling, 145, 153 lymphocytic infltration, 12 downregulated genes, 144 molecular profling of breast cancer, 17, 18 epigenetic changes, 148 progesterone receptors, 19 estrogen receptor pathway, 143 tumor grading, 11 gene methylation, 152 Progression-free survival (PFS), 38 immune response, 145 Proliferation, 164, 165, 169 long noncoding RNA in GSP of Prophylactic bilateral salpingo-­ menopausal breast, 141–143 oophorectomy, 122 parous vs. nulliparous women, 137, 138 Prophylactic mastectomy (PM), 122 RNA processing pathway and up-regulated Prosigna, 18 genes, 139 Proteomics, 180 192 Index

Q Time since last pregnancy (TSLP), 131, 133, Quadratic phenotypic optimization platform 135, 136 (QPOP), 180 TP53 mutations, 94 Transcriptional crosstalk, 13 Trastuzumab, 16, 57, 59 R Triple-negative breast cancer (TNBC), 7, 9, Radiotherapy 14, 68, 69, 76, 146 breast cancer, 55 E-cadherin, 76 Raloxifen, 13, 120 epigenetic reprograming, generalization Recombinant human chorionic of, 96–98 gonadotropin, 181 epithelial mesenchymal transition Relapse-free survival (RFS), 6 epigenetic reprogramming of, 78–91 Reproductive factor, 120, 121 molecular interpretation, epigenetic Retained intron (RI, 140 reprograming, 91–96 Retinoic acid (RA), 35 epithelial-mesenchymal transition, 76 r-hCG, 153, 154 model of, 77, 79, 80 Risk of recurrence score (ROR), 18 preclinical data, translational signifcance RTCA assay, 83 of, 98–101 Tubule-lobular carcinoma, 5 Tumor grading, 11 S Tumor suppression, 181 S-100 protein, 3 Tumorigenic bsMCF cell line, 81 Selective estrogen receptor modulators Tumorsphere formation assay, 88 (SERMs), 13, 120, 121 Tyrer-Cuzick model, 118 Sentinel node (SN) biopsy, 54 Separase, 17 SGI, 84, 90, 94 V SGI-110, 108, 113 Vimentin, 3 Single nucleotide polymorphisms (SNPs), 8 Vitamin C, 45 Smoking, 118, 119 Vitamin D, 44 Smooth muscle antigen (SMA), 4 VOLPARA, 118 Sporadic breast cancer Volpara Algorithm, 168 cancer survival in, 37, 38 Volpara® Data Manager, 167 St Gallen Consensus meeting, 12 STRIVE study, 21 Surgery, 168 W breast cancer, 54 Wnt signal transduction pathway, 140 Surrogate endpoint biomarkers (SEBs), 121 WNT/β-catenin signaling genes, 151 Surveillance, Epidemiology, and End Results Women’s Health Initiative trial, 164 database, 2 Survivin, 43 Synthetic lethality, 69 X X inactivation, 154 Xenograft, 112 T XIST, 141, 153 Talazoparib, 110, 112 XtMCF cells, 89 Tamoxifen, 13, 56, 120 Targeted drugs, 179–180 Taxanes, 56 Z TCF4, 91 Zoledronic acid, 57 Terminal ductal lobular units, 164