{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T19:17:33Z","timestamp":1777058253106,"version":"3.51.4"},"reference-count":269,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T00:00:00Z","timestamp":1627084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA179556"],"award-info":[{"award-number":["R01 CA179556"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"More for Stage IV","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Estrogen receptor alpha (ER\u03b1) marks heterogeneous breast cancers which display a repertoire of somatic genomic mutations and an immune environment that differs from other breast cancer subtypes. These cancers also exhibit distinct biological behaviors; despite an overall better prognosis than HER2+ or triple negative breast cancers, disseminated dormant cells can lead to disease recurrence decades after the initial diagnosis and treatment. Estrogen is the best studied driver of these cancers, and antagonism or reduction of estrogen activity is the cornerstone of therapeutic approaches. In addition to reducing proliferation of ER\u03b1+ cancer cells, these treatments also alter signals to multiple other target cells in the environment, including immune cell subpopulations, cancer-associated fibroblasts, and endothelial cells via several distinct estrogen receptors. In this review, we update progress in our understanding of the stromal cells populating the microenvironments of primary and metastatic ER+ tumors, the effects of estrogen on tumor and stromal cells to modulate immune activity and the extracellular matrix, and net outcomes in experimental and clinical studies. We highlight new approaches that will illuminate the unique biology of these cancers, provide the foundation for developing new treatment and prevention strategies, and reduce mortality of this disease.<\/jats:p>","DOI":"10.3390\/cancers13153725","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:06:21Z","timestamp":1627250781000},"page":"3725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers"],"prefix":"10.3390","volume":"13","author":[{"given":"Linda A.","family":"Schuler","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5724-9681","authenticated-orcid":false,"given":"Fern E.","family":"Murdoch","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer Statistics","volume":"66","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev-med-070909-182917","article-title":"Mechanisms of Endocrine Resistance in Breast Cancer","volume":"62","author":"Osborne","year":"2011","journal-title":"Annu. Rev. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/j.breast.2015.07.015","article-title":"The changing role of ER in endocrine resistance","volume":"24","author":"Nardone","year":"2015","journal-title":"Breast"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10549-015-3316-4","article-title":"Revisiting the estrogen receptor pathway and its role in endocrine therapy for postmenopausal women with estrogen receptor-positive metastatic breast cancer","volume":"150","author":"Nagaraj","year":"2015","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41568-018-0001-z","article-title":"Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance","volume":"18","author":"Katzenellenbogen","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nrc2627","article-title":"Parallel progression of primary tumours and metastases","volume":"9","author":"Klein","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.cell.2011.09.024","article-title":"Tumor Metastasis: Molecular Insights and Evolving Paradigms","volume":"147","author":"Valastyan","year":"2011","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1056\/NEJMoa1701830","article-title":"20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years","volume":"377","author":"Pan","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6389","DOI":"10.1158\/1078-0432.CCR-13-0838","article-title":"Metastasis Dormancy in Estrogen Receptor\u2013Positive Breast Cancer","volume":"19","author":"Zhang","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41416-020-01161-4","article-title":"The lingering mysteries of metastatic recurrence in breast cancer","volume":"124","author":"Riggio","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/nyas.12105","article-title":"Cancer immunoediting: Antigens, mechanisms, and implications to cancer immunotherapy","volume":"1284","author":"Vesely","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1101\/gad.314617.118","article-title":"Roles of the immune system in cancer: From tumor initiation to metastatic progression","volume":"32","author":"Gonzalez","year":"2018","journal-title":"Genes Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.immuni.2019.12.018","article-title":"Tumor Immunology and Tumor Evolution: Intertwined Histories","volume":"52","author":"Galon","year":"2020","journal-title":"Immunity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1126\/science.359.6382.1344","article-title":"The Cancer Immunotherapy Revolution","volume":"359","author":"Kelly","year":"2018","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0191-1","article-title":"Immune checkpoint inhibitors: Recent progress and potential biomarkers","volume":"50","author":"Darvin","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-17670-y","article-title":"A decade of immune-checkpoint inhibitors in cancer therapy","volume":"11","author":"Robert","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1158\/2326-6066.CIR-15-0149","article-title":"Immunogenic Subtypes of Breast Cancer Delineated by Gene Classifiers of Immune Responsiveness","volume":"4","author":"Miller","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.breast.2016.07.015","article-title":"The genomic landscape of breast cancer and its interaction with host immunity","volume":"29","author":"Luen","year":"2016","journal-title":"Breast"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ctrv.2016.03.011","article-title":"The immune system and hormone-receptor positive breast cancer: Is it really a dead end?","volume":"46","author":"Dieci","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1158\/1078-0432.CCR-16-2569","article-title":"Immunotherapy for Breast Cancer: What Are We Missing?","volume":"23","author":"Vonderheide","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-018-0126-6","article-title":"Checkpoint blockade in the treatment of breast cancer: Current status and future directions","volume":"119","author":"Wein","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1210\/er.2007-0001","article-title":"The Complex Role of Estrogens in Inflammation","volume":"28","author":"Straub","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.mce.2013.06.003","article-title":"The immune system and inflammation in breast cancer","volume":"382","author":"Jiang","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cellimm.2015.01.018","article-title":"Estrogen receptors regulate innate immune cells and signaling pathways","volume":"294","author":"Kovats","year":"2015","journal-title":"Cell. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.tem.2011.12.001","article-title":"microRNAs, and the epithelial-mesenchymal transition in breast cancer","volume":"23","author":"Guttilla","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.mce.2012.08.016","article-title":"Estrogens promote cell\u2013cell adhesion of normal and malignant mammary cells through increased desmosome formation","volume":"364","author":"Maynadier","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"T177","DOI":"10.1530\/ERC-15-0350","article-title":"The role of steroid hormones in breast cancer stem cells","volume":"22","author":"Alferez","year":"2015","journal-title":"Endocr. Related Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1038\/onc.2017.94","article-title":"Estrogen receptors in breast and bone: From virtue of remodeling to vileness of metastasis","volume":"36","author":"Bado","year":"2017","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1002\/jbmr.3618","article-title":"Understanding the Bone in Cancer Metastasis","volume":"33","author":"Fornetti","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-030-50224-9_2","article-title":"The Impact of Estrogen in the Tumor Microenvironment","volume":"1277","author":"Somasundaram","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3389\/fimmu.2019.00348","article-title":"Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology","volume":"10","year":"2019","journal-title":"Front Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-020-01788-4","article-title":"The immunomodulatory effects of endocrine therapy in breast cancer","volume":"40","author":"Huang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1001\/jamaoncol.2016.1061","article-title":"Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: A systematic review","volume":"2","author":"Stanton","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_34","first-page":"615","article-title":"The single-cell pathology landscape of breast cancer","volume":"578","author":"Jackson","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13058-019-1239-4","article-title":"Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer","volume":"21","author":"Nederlof","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_36","first-page":"a003293","article-title":"Systems Biology and Genomics of Breast Cancer","volume":"3","author":"Perou","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_37","first-page":"346","article-title":"he genomic and transcriptomic architecture of 2000 breast tumours reveals novel subgroups","volume":"486","author":"Curtis","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/cjp2.25","article-title":"Classical pathology and mutational load of breast cancer\u2014Integration of two worlds","volume":"1","author":"Budczies","year":"2015","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.imlet.2004.10.007","article-title":"Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations","volume":"97","author":"Phiel","year":"2005","journal-title":"Immunol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1756-9966-29-80","article-title":"Breast cancer stromal fibroblasts promote the generation of CD44+CD24- cells through SDF-1\/CXCR4 interaction","volume":"29","author":"Huang","year":"2010","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.imlet.2010.06.003","article-title":"Estrogen receptor profiles in human peripheral blood lymphocytes","volume":"132","author":"Pierdominici","year":"2010","journal-title":"Immunol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1158\/2159-8290.CD-16-0502","article-title":"Tumor Cell\u2013Independent Estrogen Signaling Drives Disease Progression through Mobilization of Myeloid-Derived Suppressor Cells","volume":"7","author":"Svoronos","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pepermans, R., Sharma, G., and Prossnitz, E. (2021). G Protein-Coupled Estrogen Receptor in Cancer and Stromal Cells: Functions and Novel Therapeutic Perspectives. Cells, 10.","DOI":"10.3390\/cells10030672"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.cell.2019.03.005","article-title":"A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer","volume":"177","author":"Wagner","year":"2019","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e107333","DOI":"10.15252\/embj.2020107333","article-title":"A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast","volume":"40","author":"Pal","year":"2021","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S1470-2045(17)30904-X","article-title":"Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: A pooled analysis of 3771 patients treated with neoadjuvant therapy","volume":"19","author":"Denkert","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1200\/JCO.2011.41.0902","article-title":"Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes in a Phase III Randomized Adjuvant Breast Cancer Trial in Node-Positive Breast Cancer Comparing the Addition of Docetaxel to Doxorubicin With Doxorubicin-Based Chemotherapy: BIG 02-98","volume":"31","author":"Loi","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13058-020-01364-w","article-title":"Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer: Data from a randomised trial with long-term follow-up","volume":"22","author":"Lundgren","year":"2020","journal-title":"Breast Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1172\/JCI96313","article-title":"Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers","volume":"129","author":"Gruosso","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1158\/1078-0432.CCR-17-3452","article-title":"Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor\u2013Positive\/Human Epidermal Growth Factor Receptor 2\u2013Negative Advanced Breast Cancer","volume":"24","author":"Rugo","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s10549-017-4537-5","article-title":"Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase 1b JAVELIN Solid Tumor study","volume":"167","author":"Dirix","year":"2017","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4644","DOI":"10.1158\/1078-0432.CCR-19-0173","article-title":"The Immune Microenvironment in Hormone Receptor\u2013Positive Breast Cancer Before and After Preoperative Chemotherapy","volume":"25","author":"Waks","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41568-019-0235-4","article-title":"CD8+ T cell states in human cancer: Insights from single-cell analysis","volume":"20","author":"Thommen","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1158\/1078-0432.CCR-19-0285","article-title":"Clonality, antigen recognition, and suppression of CD8(+) T Cells differentially affect prognosis of breast dancer subtypes","volume":"26","author":"Hammerl","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.semcancer.2017.11.003","article-title":"Breast cancer genomics and immuno-oncological markers to guide immune therapies","volume":"52","author":"Hammerl","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T Cells: Mechanisms of Differentiation and Function","volume":"30","author":"Josefowicz","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13058-014-0432-8","article-title":"Prognostic significance of FOXP3+ tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration","volume":"16","author":"Liu","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.ejso.2017.01.011","article-title":"High tumor-infiltrating FoxP3 + T cells predict poor survival in estrogen receptor-positive breast cancer: A meta-analysis","volume":"43","author":"Qian","year":"2017","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-015-1742-7","article-title":"Clinicopathological and prognostic significance of FOXP3+ tumor infiltrating lymphocytes in patients with breast cancer: A meta-analysis","volume":"15","author":"Jiang","year":"2015","journal-title":"BMC Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/nri3904","article-title":"Gammadelta T cells in cancer","volume":"15","author":"Serre","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.trsl.2018.08.005","article-title":"The role of gamma delta T lymphocytes in breast cancer: A review","volume":"203","author":"Morrow","year":"2019","journal-title":"Transl. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.3389\/fimmu.2020.02186","article-title":"Pro-tumor gammadelta T Cells in human cancer: Polarization, mechanisms of action, and implications for therapy","volume":"11","author":"Chabab","year":"2020","journal-title":"Front Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1158\/0008-5472.CAN-13-0348","article-title":"Specific recruitment of gammadelta regulatory T cells in human breast cancer","volume":"73","author":"Ye","year":"2013","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41573-019-0038-z","article-title":"Translating gammadelta (\u03b3\u03b4) T cells and their receptors into cancer cell therapies","volume":"19","author":"Sebestyen","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e129641","DOI":"10.1172\/jci.insight.129641","article-title":"Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer","volume":"4","author":"Garaud","year":"2019","journal-title":"JCI Insight"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"O\u2019Meara, T., Marczyk, M., Qing, T., Yaghoobi, V., Blenman, K., Cole, K., Pelekanou, V., Rimm, D.L., and Pusztai, L. (2020). Immunological Differences Between Immune-Rich Estrogen Receptor\u2013Positive and Immune-Rich Triple-Negative Breast Cancers. JCO Precis. Oncol., 767\u2013779.","DOI":"10.1200\/PO.19.00350"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s12282-018-0910-4","article-title":"Coexistence of regulatory B cells and regulatory T cells in tumor-infiltrating lymphocyte aggregates is a prognostic factor in patients with breast cancer","volume":"26","author":"Ishigami","year":"2018","journal-title":"Breast Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cell.2018.05.060","article-title":"Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment","volume":"174","author":"Azizi","year":"2018","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/jnci\/djz213","article-title":"Immune Checkpoint Profiles in Luminal B Breast Cancer (Alliance)","volume":"112","author":"Anurag","year":"2019","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1158\/1078-0432.CCR-15-0204","article-title":"CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer","volume":"21","author":"Svensson","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/imr.12223","article-title":"Macrophage heterogeneity in tissues: Phenotypic diversity and functions","volume":"262","author":"Gordon","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41577-019-0127-6","article-title":"Macrophages as regulators of tumour immunity and immunotherapy","volume":"19","author":"DeNardo","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/JLB.MR0218-056RR","article-title":"The emerging roles of macrophages in cancer metastasis and response to chemotherapy","volume":"106","author":"Sanchez","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, Mechanisms, and Significance of Macrophage Plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"a038026","DOI":"10.1101\/cshperspect.a038026","article-title":"Myeloid cells in metastasis","volume":"10","author":"Swierczak","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"787","DOI":"10.3389\/fonc.2020.00787","article-title":"Biomechanical Contributions to Macrophage Activation in the Tumor Microenvironment","volume":"10","author":"Hoffmann","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6166","DOI":"10.4049\/jimmunol.164.12.6166","article-title":"M-1\/M-2 macrophages and the Th1\/Th2 paradigm","volume":"164","author":"Mills","year":"2000","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 paradigm of macrophage activation: Time for reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000 Prime Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.immuni.2014.01.006","article-title":"Transcriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation","volume":"40","author":"Xue","year":"2014","journal-title":"Immunity"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15081","DOI":"10.1038\/ncomms15081","article-title":"Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer","volume":"8","author":"Chung","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"108482","DOI":"10.1016\/j.celrep.2020.108482","article-title":"Regulatory T cells support breast cancer progression by opposing IFN-gamma-dependent functional reprogramming of myeloid cells","volume":"33","author":"Clark","year":"2020","journal-title":"Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13058-018-1076-x","article-title":"CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers","volume":"20","author":"Pelekanou","year":"2018","journal-title":"Breast Cancer Res."},{"key":"ref_83","first-page":"srep09188","article-title":"Characterization of macrophage\u2014cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer","volume":"5","author":"Roudnicky","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_84","first-page":"e1115177","article-title":"G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer","volume":"5","author":"Karaman","year":"2015","journal-title":"Onco. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4049\/jimmunol.1701019","article-title":"Myeloid-Derived Suppressor Cells: Immune-Suppressive Cells That Impair Antitumor Immunity and Are Sculpted by Their Environment","volume":"200","author":"Fenselau","year":"2018","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.immuni.2021.01.012","article-title":"Chemokines and the immune response to cancer","volume":"54","author":"Ozga","year":"2021","journal-title":"Immunity"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10248","DOI":"10.1038\/ncomms10248","article-title":"Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles","volume":"7","author":"Varn","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"R123","DOI":"10.1530\/ERC-16-0404","article-title":"The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy","volume":"24","author":"Law","year":"2017","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Ali, H.R., Chlon, L., Pharoah, P.D.P., Markowetz, F., and Caldas, C. (2016). Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002194"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00262-019-02472-z","article-title":"Clinical relevance of systemic monocytic-MDSCs in patients with metastatic breast cancer","volume":"69","author":"Bergenfelz","year":"2020","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.3389\/fimmu.2020.01779","article-title":"A Rosetta Stone for Breast Cancer: Prognostic Value and Dynamic Regulation of Neutrophil in Tumor Microenvironment","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41590-018-0145-8","article-title":"Adjustment of dendritic cells to the breast-cancer microenvironment is subset specific","volume":"19","author":"Michea","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/B978-0-12-800267-4.00003-1","article-title":"Recognition of Tumors by the Innate Immune System and Natural Killer Cells","volume":"122","author":"Marcus","year":"2014","journal-title":"Adv. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Franks, S.E., Wolfson, B., and Hodge, J.W. (2020). Natural Born Killers: NK Cells in Cancer Therapy. Cancers, 12.","DOI":"10.20944\/preprints202007.0139.v1"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.immuni.2018.03.004","article-title":"Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape","volume":"48","author":"Wellenstein","year":"2018","journal-title":"Immunity"},{"key":"ref_96","first-page":"1","article-title":"Cancer-immune interactions in ER-positive breast cancers: PI3K pathway alterations and tumor-infiltrating lymphocytes","volume":"21","author":"Salomon","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4960","DOI":"10.1158\/0008-5472.CAN-14-2992","article-title":"Ras Signaling Is a Key Determinant for Metastatic Dissemination and Poor Survival of Luminal Breast Cancer Patients","volume":"75","author":"Wright","year":"2015","journal-title":"Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1158\/2159-8290.CD-16-0520","article-title":"Loss of RasGAP Tumor Suppressors Underlies the Aggressive Nature of Luminal B Breast Cancers","volume":"7","author":"Olsen","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ccell.2018.08.008","article-title":"The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers","volume":"34","author":"Razavi","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_100","first-page":"560","article-title":"Genomic characterization of metastatic breast cancers","volume":"569","author":"Bertucci","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1038\/s41467-018-05914-x","article-title":"The prognostic effects of somatic mutations in ER-positive breast cancer","volume":"9","author":"Griffith","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"a031849","DOI":"10.1101\/cshperspect.a031849","article-title":"Kras and Tumor Immunity: Friend or Foe?","volume":"8","author":"Cullis","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1158\/0008-5472.CAN-17-2084","article-title":"KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment","volume":"78","author":"Carvalho","year":"2017","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-19288-6","article-title":"Immune modulatory effects of oncogenic KRAS in cancer","volume":"11","author":"Hamarsheh","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1093\/annonc\/mdy399","article-title":"Immunological differences between primary and metastatic breast cancer","volume":"29","author":"Szekely","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s40425-019-0755-1","article-title":"Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors","volume":"7","author":"Zhu","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1158\/0008-5472.CAN-20-1200","article-title":"Steroid Hormone Receptor and Infiltrating Immune Cell Status Reveals Therapeutic Vulnerabilities of ESR1-Mutant Breast Cancer","volume":"81","author":"Williams","year":"2020","journal-title":"Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1158\/0008-5472.CAN-07-5644","article-title":"Subtypes of Breast Cancer Show Preferential Site of Relapse","volume":"68","author":"Smid","year":"2008","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1200\/JCO.2009.25.9820","article-title":"Metastatic Behavior of Breast Cancer Subtypes","volume":"28","author":"Kennecke","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00428-017-2065-7","article-title":"Breast carcinoma subtypes show different patterns of metastatic behavior","volume":"470","author":"Fekete","year":"2017","journal-title":"Virchows Archiv."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Lee, H., Na, K.J., and Choi, H. (2021). Differences in Tumor Immune Microenvironment in Metastatic Sites of Breast Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.649004"},{"key":"ref_112","first-page":"1","article-title":"CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer","volume":"12","author":"Vermeer","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fonc.2017.00163","article-title":"Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?","volume":"7","author":"Lin","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/path.5292","article-title":"From latency to overt bone metastasis in breast cancer: Potential for treatment and prevention","volume":"249","author":"Salvador","year":"2019","journal-title":"J. Pathol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.coph.2010.09.007","article-title":"The molecular mechanisms underlying the pharmacological actions of ER modulators: Implications for new drug discovery in breast cancer","volume":"10","author":"McDonnell","year":"2010","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1530\/JME-16-0024","article-title":"Antiestrogens: Structure-Activity relationships and use in breast cancer treatment","volume":"58","author":"Traboulsi","year":"2017","journal-title":"J. Mol. Endocrinol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nm.1945","article-title":"Estrogen-dependent and C-C chemokine receptor-2\u2013dependent pathways determine osteoclast behavior in osteoporosis","volume":"15","author":"Binder","year":"2009","journal-title":"Nat. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"561595","DOI":"10.3389\/fonc.2020.561595","article-title":"Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer","volume":"10","author":"Liu","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.devcel.2021.03.008","article-title":"The bone microenvironment increases phenotypic plasticity of ER+ breast cancer cells","volume":"56","author":"Bado","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1200\/JCO.1999.17.5.1474","article-title":"Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer","volume":"17","author":"Harvey","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/jnci\/djx137","article-title":"Relevance of Spatial Heterogeneity of Immune Infiltration for Predicting Risk of Recurrence After Endocrine Therapy of ER+ Breast Cancer","volume":"110","author":"Heindl","year":"2017","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10911-011-9226-0","article-title":"Mechanisms by Which the Extracellular Matrix and Integrin Signaling Act to Regulate the Switch Between Tumor Suppression and Tumor Promotion","volume":"16","author":"Keely","year":"2011","journal-title":"J. Mammary Gland. Biol. Neoplasia"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.15252\/embr.201439246","article-title":"The extracellular matrix modulates the hallmarks of cancer","volume":"15","author":"Pickup","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41416-020-01172-1","article-title":"The fibrotic and immune microenvironments as targetable drivers of metastasis","volume":"124","author":"Boulter","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-18794-x","article-title":"Concepts of extracellular matrix remodelling in tumour progression and metastasis","volume":"11","author":"Winkler","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s10555-018-9768-3","article-title":"Cancer-associated fibroblasts as key regulators of the breast cancer tumor microenvironment","volume":"37","author":"Houthuijzen","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1158\/2326-6066.CIR-20-0070","article-title":"Immune Remodeling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection","volume":"8","author":"Pires","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41563-020-00849-5","article-title":"Tumour-associated macrophages drive stromal cell-dependent collagen crosslinking and stiffening to promote breast cancer aggression","volume":"20","author":"Maller","year":"2020","journal-title":"Nat. Mater."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-31126-w","article-title":"Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma","volume":"8","author":"Tomko","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s10555-016-9650-0","article-title":"From transformation to metastasis: Deconstructing the extracellular matrix in breast cancer","volume":"35","author":"Kaushik","year":"2016","journal-title":"Cancer Metastasis Rev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/ncb2767","article-title":"The perivascular niche regulates breast tumour dormancy","volume":"15","author":"Ghajar","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/19336918.2015.1008331","article-title":"Tenascin C in metastasis: A view from the invasive front","volume":"9","author":"Lowy","year":"2015","journal-title":"Cell Adhes. Migr."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.devcel.2019.04.011","article-title":"Exosome-Mediated Metastasis: Communication from a Distance","volume":"49","author":"Wortzel","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41563-020-0615-x","article-title":"Reprogramming normal cells into tumour precursors requires ECM stiffness and oncogene-mediated changes of cell mechanical properties","volume":"19","author":"Panciera","year":"2020","journal-title":"Nat. Mater."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.cell.2009.10.027","article-title":"Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling","volume":"139","author":"Levental","year":"2009","journal-title":"Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"48093","DOI":"10.18632\/oncotarget.10137","article-title":"Prolactin signaling through focal adhesion complexes is amplified by stiff extracellular matrices in breast cancer cells","volume":"7","author":"Barcus","year":"2016","journal-title":"Oncotarget"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13058-017-0801-1","article-title":"Elevated collagen-I augments tumor progressive signals, intravasation and metastasis of prolactin-induced estrogen receptor alpha positive mammary tumor cells","volume":"19","author":"Barcus","year":"2017","journal-title":"Breast Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s40425-018-0376-0","article-title":"Tumor matrix remodeling and novel immunotherapies: The promise of matrix-derived immune biomarkers","volume":"6","author":"Mushtaq","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the Roots of Cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2018.06.025","article-title":"High collagen density augments mTOR-dependent cancer stem cells in ER\u03b1+ mammary carcinomas and increases mTOR-independent lung metastases","volume":"433","author":"Shea","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1158\/1541-7786.MCR-19-0375","article-title":"The Emerging Role of YAP\/TAZ in Tumor Immunity","volume":"17","author":"Pan","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Morciano, G., Vezzani, B., Missiroli, S., Boncompagni, C., Pinton, P., and Giorgi, C. (2021). An Updated Understanding of the Role of YAP in Driving Oncogenic Responses. Cancers, 13.","DOI":"10.3390\/cancers13123100"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"20180214","DOI":"10.1098\/rstb.2018.0214","article-title":"Immunotherapy: Breaching the barriers for cancer treatment","volume":"374","author":"Martinez","year":"2019","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.ajpath.2010.11.076","article-title":"Aligned Collagen Is a Prognostic Signature for Survival in Human Breast Carcinoma","volume":"178","author":"Conklin","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1741-7015-4-38","article-title":"Collagen reorganization at the tumor-stromal interface facilitates local invasion","volume":"4","author":"Provenzano","year":"2006","journal-title":"BMC Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ajpath.2017.10.025","article-title":"The Presence of Cyclooxygenase 2, Tumor-Associated Macrophages, and Collagen Alignment as Prognostic Markers for Invasive Breast Carcinoma Patients","volume":"188","author":"Esbona","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1158\/1078-0432.CCR-15-2851","article-title":"Fibroblast Subtypes Regulate Responsiveness of Luminal Breast Cancer to Estrogen","volume":"23","author":"Brechbuhl","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41573-018-0004-1","article-title":"Turning foes to friends: Targeting cancer-associated fibroblasts","volume":"18","author":"Chen","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","article-title":"A framework for advancing our understanding of cancer-associated fibroblasts","volume":"20","author":"Sahai","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1158\/2159-8290.CD-20-1808","article-title":"Therapeutic Targeting of the Tumor Microenvironment","volume":"11","author":"Bejarano","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"e130751","DOI":"10.1172\/jci.insight.130751","article-title":"Fibroblast subtypes define a metastatic matrisome in breast cancer","volume":"5","author":"Brechbuhl","year":"2020","journal-title":"JCI Insight"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41467-019-14134-w","article-title":"Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms","volume":"11","author":"Pelon","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Barcus, C.E., Holt, E.C., Keely, P.J., Eliceiri, K.W., and Schuler, L.A. (2015). Dense Collagen-I Matrices Enhance Pro-Tumorigenic Estrogen-Prolactin Crosstalk in MCF-7 and T47D Breast Cancer Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116891"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"6913","DOI":"10.1038\/s41388-019-0941-0","article-title":"Dynamic interactions between the extracellular matrix and estrogen activity in progression of ER+ breast cancer","volume":"38","author":"Jallow","year":"2019","journal-title":"Oncogene"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e46557","DOI":"10.15252\/embr.201846557","article-title":"Tamoxifen mechanically reprograms the tumor microenvironment via HIF\u20131A and reduces cancer cell survival","volume":"20","author":"Cortes","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1038\/sj.bjc.6602688","article-title":"Role of aromatase inhibitors in breast cancer","volume":"93","author":"Carpenter","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1056\/NEJMra023246","article-title":"Aromatase Inhibitors in Breast Cancer","volume":"348","author":"Smith","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.ejca.2004.07.035","article-title":"Endocrine treatment options for advanced breast cancer\u2014The role of fulvestrant","volume":"41","author":"Robertson","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41416-018-0354-9","article-title":"The oral selective oestrogen receptor degrader (SERD) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance","volume":"120","author":"Nardone","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"105415","DOI":"10.1016\/j.jsbmb.2019.105415","article-title":"Antiestrogens in combination with immune checkpoint inhibitors in breast cancer immunotherapy","volume":"193","author":"Deng","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1101\/gad.1944810","article-title":"Growth factor stimulation induces a distinct ER cistrome underlying breast cancer endocrine resistance","volume":"24","author":"Lupien","year":"2010","journal-title":"Genes Dev."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature14583","article-title":"Progesterone receptor modulates ER alpha action in breast cancer","volume":"523","author":"Mohammed","year":"2015","journal-title":"Nature"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41591-020-01168-7","article-title":"The androgen receptor is a tumor suppressor in estrogen receptor\u2013positive breast cancer","volume":"27","author":"Hickey","year":"2021","journal-title":"Nat. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1101\/gad.316646.118","article-title":"Signaling pathways and steroid receptors modulating estrogen receptor \u03b1 function in breast cancer","volume":"32","author":"Kumar","year":"2018","journal-title":"Genes Dev."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"bqaa224","DOI":"10.1210\/endocr\/bqaa224","article-title":"Genome-Wide Estrogen Receptor Activity in Breast Cancer","volume":"162","author":"Farcas","year":"2020","journal-title":"Endocrinol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.molcel.2015.02.001","article-title":"Signaling exposes latent estrogen receptor binding sites to alter the breast cancer cell transcriptome","volume":"58","author":"Franco","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.mce.2014.09.013","article-title":"NFkB affects estrogen receptor expression and activity in breast cancer through multiple mechanisms","volume":"418","author":"Frasor","year":"2015","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.ccell.2020.06.007","article-title":"IL6\/STAT3 Signaling Hijacks Estrogen Receptor \u03b1 Enhancers to Drive Breast Cancer Metastasis","volume":"38","author":"Scabia","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.molcel.2017.02.008","article-title":"Structural and Molecular Mechanisms of Cytokine-Mediated Endocrine Resistance in Human Breast Cancer Cells","volume":"65","author":"Stender","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.cmet.2020.05.008","article-title":"The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development","volume":"31","author":"Qureshi","year":"2020","journal-title":"Cell Metab."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nri.2017.142","article-title":"NF-kB, inflammation, immunity and cancer: Coming of age","volume":"18","author":"Taniguchi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1158\/1541-7786.MCR-19-1082","article-title":"The NF-kB pathway promotes tamoxifen tolerance and disease recurrence in estrogen receptor-positive breast cancers","volume":"18","author":"Kastrati","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/bjc.2013.24","article-title":"Exploiting inflammation for therapeutic gain in pancreatic cancer","volume":"108","author":"Steele","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11912-017-0591-8","article-title":"The evolving role of the estrogen receptor mutations in endocrine therapy-resistant creast cancer","volume":"19","author":"Jeselsohn","year":"2017","journal-title":"Curr. Oncol. Rep."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13058-017-0851-4","article-title":"Mutation site and context dependent effects of ESR1 mutation in genome-edited breast cancer cell models","volume":"19","author":"Bahreini","year":"2017","journal-title":"Breast Cancer Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ccell.2018.01.004","article-title":"Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations","volume":"33","author":"Jeselsohn","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10549-020-05629-y","article-title":"Suppression of breast cancer metastasis and extension of survival by a new antiestrogen in a preclinical model driven by mutant estrogen receptors","volume":"181","author":"Laws","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41523-019-0109-7","article-title":"Estrogen receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers","volume":"5","author":"Groenendijk","year":"2019","journal-title":"NPJ Breast Cancer"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41523-020-0151-5","article-title":"The therapeutic response of ER+\/HER2\u2212 breast cancers differs according to the molecular Basal or Luminal subtype","volume":"6","author":"Bertucci","year":"2020","journal-title":"NPJ Breast Cancer"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00026.2006","article-title":"Estrogen Receptors: How Do They Signal and What Are Their Targets","volume":"87","author":"Heldring","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1073\/pnas.1323719111","article-title":"Differential expression of estrogen receptor alpha, beta1, and beta2 in lobular and ductal breast cancer","volume":"111","author":"Huang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s10549-019-05441-3","article-title":"Optimized immunohistochemical detection of estrogen receptor beta using two validated monoclonal antibodies confirms its expression in normal and malignant breast tissues","volume":"179","author":"Hawse","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1210\/en.2006-0563","article-title":"Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells","volume":"147","author":"Chang","year":"2006","journal-title":"Endocrinology"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.mce.2013.08.005","article-title":"Estrogen receptor beta in breast cancer","volume":"382","author":"Zhao","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"587386","DOI":"10.3389\/fonc.2020.587386","article-title":"Estrogen Receptor Beta (ERbeta): A Ligand Activated Tumor Suppressor","volume":"10","author":"Mal","year":"2020","journal-title":"Front Oncol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1124\/mol.54.1.105","article-title":"Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists\/antagonists","volume":"54","author":"Barkhem","year":"1998","journal-title":"Mol. Pharmacol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1126\/science.277.5331.1508","article-title":"Differential ligand activation of estrogen receptors ER alpha and ER beta at AP1 sites","volume":"277","author":"Paech","year":"1997","journal-title":"Science"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1677\/jme.0.0320987","article-title":"Distinct effects of the antiestrogen Faslodex on the stability of estrogen receptors-alpha and -beta in the breast cancer cell line MCF-7","volume":"32","author":"Peekhaus","year":"2004","journal-title":"J. Mol. Endocrinol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10549-014-2936-4","article-title":"Lack of G protein-coupled estrogen receptor (GPER) in the plasma membrane is associated with excellent long-term prognosis in breast cancer","volume":"145","author":"Hartman","year":"2014","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10549-018-5064-8","article-title":"G-protein-coupled estrogen receptor GPER-1 expression in hormone receptor-positive breast cancer is associated with poor benefit of tamoxifen","volume":"174","author":"Ignatov","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Hsu, L.-H., Chu, N.-M., Lin, Y.-F., and Kao, S.-H. (2019). G-Protein Coupled Estrogen Receptor in Breast Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020306"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"24354","DOI":"10.1038\/srep24354","article-title":"GPER signalling in both cancer-associated fibroblasts and breast cancer cells mediates a feedforward IL1beta\/IL1R1 response","volume":"6","author":"Lappano","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"e46556","DOI":"10.15252\/embr.201846556","article-title":"GPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment","volume":"20","author":"Cortes","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/CJI.0b013e31828d8e3b","article-title":"The G Protein-coupled Estrogen Receptor (GPER) Agonist G-1 Expands the Regulatory T-cell Population Under TH17-polarizing Conditions","volume":"36","author":"Brunsing","year":"2013","journal-title":"J. Immunother."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1126\/science.aba9001","article-title":"GPER1 is required to protect fetal health from maternal inflammation","volume":"371","author":"Harding","year":"2021","journal-title":"Science"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10549-011-1611-2","article-title":"Androgens and musculoskeletal symptoms among breast cancer patients on aromatase inhibitor therapy","volume":"130","author":"Gallicchio","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: Archive for functional genomics data sets\u2013update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1210\/me.2002-0438","article-title":"Stromal Cell-Derived Factor 1, a Novel Target of Estrogen Receptor Action, Mediates the Mitogenic Effects of Estradiol in Ovarian and Breast Cancer Cells","volume":"17","author":"Hall","year":"2003","journal-title":"Mol. Endocrinol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1158\/0008-5472.CAN-03-3326","article-title":"Selective estrogen receptor modulators: Discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells","volume":"64","author":"Frasor","year":"2004","journal-title":"Cancer Res."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1124\/mol.107.039974","article-title":"17beta-estradiol promotes breast cancer cell proliferation-inducing stromal cell-derived factor-1-mediated epidermal growth factor receptor transactivation: Reversal by gefitinib pretreatment","volume":"73","author":"Pattarozzi","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1093\/carcin\/bgz176","article-title":"Arsenite and cadmium promote the development of mammary tumors","volume":"41","author":"Divekar","year":"2019","journal-title":"Carcinogenesis"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.gdata.2015.05.040","article-title":"Expression profiling of genes modulated by estrogen, EGCG or both in MCF-7 breast cancer cells","volume":"5","author":"Manjegowda","year":"2015","journal-title":"Genom. Data"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/onc.2013.579","article-title":"Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes","volume":"34","author":"Daniel","year":"2014","journal-title":"Oncogene"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"LeComte, S., DeMay, F., Pham, T.H., Moulis, S., Efstathiou, T., Chalmel, F., and Pakdel, F. (2019). Deciphering the Molecular Mechanisms Sustaining the Estrogenic Activity of the Two Major Dietary Compounds Zearalenone and Apigenin in ER-Positive Breast Cancer Cell Lines. Nutr., 11.","DOI":"10.3390\/nu11020237"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"5634","DOI":"10.1158\/0008-5472.CAN-15-2910","article-title":"Estrogen Receptor \u03b1 Promotes Breast Cancer by Reprogramming Choline Metabolism","volume":"76","author":"Jia","year":"2016","journal-title":"Cancer Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bbrc.2012.08.007","article-title":"Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells","volume":"426","author":"Putnik","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_207","first-page":"620","article-title":"Fasting-mimicking diet and hormone therapy induce breast cancer regression","volume":"583","author":"Caffa","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.1158\/0008-5472.CAN-06-3696","article-title":"Novel Estrogen Receptor-\u03b1 Binding Sites and Estradiol Target Genes Identified by Chromatin Immunoprecipitation Cloning in Breast Cancer","volume":"67","author":"Lin","year":"2007","journal-title":"Cancer Res."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Zieli\u0144ska, K.A., and Katanaev, V.L. (2020). The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis. Cancers, 12.","DOI":"10.3390\/cancers12103071"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Kohli, K., Pillarisetty, V.G., and Kim, T.S. (2021). Key chemokines direct migration of immune cells in solid tumors. Cancer Gene Ther., 1\u201312.","DOI":"10.1038\/s41417-021-00303-x"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"117534","DOI":"10.1016\/j.lfs.2020.117534","article-title":"CXCL12\/CXCR4 axis in the microenvironment of solid tumors: A critical mediator of metastasis","volume":"249","author":"Mortezaee","year":"2020","journal-title":"Life Sci."},{"key":"ref_212","first-page":"13217","article-title":"Prognostic significance of CXCL12, CXCR4, and CXCR7 in patients with breast cancer","volume":"8","author":"Wu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1038\/s41388-018-0263-7","article-title":"Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation","volume":"37","author":"Ahirwar","year":"2018","journal-title":"Oncogene"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.canlet.2008.03.018","article-title":"The inflammatory chemokines CCL2 and CCL5 in breast cancer","volume":"267","author":"Soria","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrc2853","article-title":"TGFbeta signalling: A complex web in cancer progression","volume":"10","author":"Ikushima","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/bjc.2016.255","article-title":"Transforming growth factor beta as regulator of cancer stemness and metastasis","volume":"115","author":"Bellomo","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41580-018-0007-0","article-title":"Contextual determinants of TGFbeta action in development, immunity and cancer","volume":"19","author":"David","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_218","first-page":"a003277","article-title":"TGF-beta biology in mammary development and breast cancer","volume":"3","author":"Moses","year":"2011","journal-title":"Cold Spring Harbor Perspect Bio."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1158\/0008-5472.CAN-09-3292","article-title":"Antiestrogens induce transforming growth factor beta-mediated immunosuppression in breast cancer","volume":"70","author":"Joffroy","year":"2010","journal-title":"Cancer Res."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"a028548","DOI":"10.1101\/cshperspect.a028548","article-title":"Targeting IL-10 Family Cytokines for the Treatment of Human Diseases","volume":"11","author":"Wang","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.3389\/fimmu.2019.01976","article-title":"Editorial: The IL-20 Cytokines and Related Family Members in Immunity and Diseases","volume":"10","author":"Niess","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-18244-8","article-title":"IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models","volume":"11","author":"Lu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10549-013-2716-6","article-title":"Distinct nuclear receptor expression in stroma adjacent to breast tumors","volume":"142","author":"Knower","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1158\/0008-5472.CAN-20-1705","article-title":"Fulvestrant-Mediated Attenuation of the Innate Immune Response Decreases ER+ Breast Cancer Growth In Vivo More Effectively than Tamoxifen","volume":"80","author":"Abrahamsson","year":"2020","journal-title":"Cancer Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10911-020-09452-5","article-title":"Weighing the Risk: Effects of Obesity on the Mammary Gland and Breast Cancer Risk","volume":"25","author":"Arendt","year":"2020","journal-title":"J. Mammary Gland. Biol. Neoplasia"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/1547691X.2014.899411","article-title":"Estrogen-mediated impairment of macrophageal uptake of environmental TiO2particles to explain inflammatory effect of TiO2on airways during pregnancy","volume":"12","author":"Zhang","year":"2014","journal-title":"J. Immunotoxicol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1182\/blood-2009-08-236935","article-title":"Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4","volume":"115","author":"Carreras","year":"2010","journal-title":"Blood"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1089\/scd.2007.0251","article-title":"Estrogen-Induced Gene Expression in Bone Marrow c-kit+ Stem Cells and Stromal Cells: Identification of Specific Biological Processes Involved in the Functional Organization of the Stem Cell Niche","volume":"17","author":"Lemieux","year":"2008","journal-title":"Stem Cells Dev."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1093\/humrep\/dev067","article-title":"Estrogen-dependent regulation of human uterine natural killer cells promotes vascular remodelling via secretion of CCL2","volume":"30","author":"Gibson","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/jcp.21221","article-title":"Induction of regulatory T cells by physiological level estrogen","volume":"214","author":"Tai","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Bai, J., Qi, Q.-R., Li, Y., Day, R., Makhoul, J., Magness, R.R., and Chen, D.-B. (2020). Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124349"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.cjca.2013.08.006","article-title":"Mechanisms of Estrogen Effects on the Endothelium: An Overview","volume":"30","author":"Chakrabarti","year":"2014","journal-title":"Can. J. Cardiol."},{"key":"ref_233","unstructured":"Bowman, P.D., Zhao, B., and Bynum, J.A. (2021, May 23). NCBI GEO Database GSE1486, GSE59558, GSE59558, GSE59558, GSE52649, Available online: https:\/\/www.ncbi.nlm.nih.gov\/geo\/."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Sobrino, A., Mata, M., Laguna-Fern\u00e1ndez, A., Novella, S., Oviedo, P.J., Garc\u00eda-P\u00e9rez, M.A., Tar\u00edn, J.J., Ca\u00f1o, A., and Hermenegildo, C. (2009). Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008242"},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger-Genge, A., Blocki, A., Franke, R.-P., and Jung, F. (2019). Vascular Endothelial Cell Biology: An Update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184411"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41576-020-00292-x","article-title":"Deciphering cell\u2013cell interactions and communication from gene expression","volume":"22","author":"Armingol","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"bqaa152","DOI":"10.1210\/endocr\/bqaa152","article-title":"Update on the role of NFkappaB in promoting aggressive phenotypes of estrogen receptor-positive breast cancer","volume":"161","author":"Smart","year":"2020","journal-title":"Endocrinology"},{"key":"ref_238","first-page":"201","article-title":"Modeling Prolactin Actions in Breast Cancer In Vivo: Insights from the NRL-PRL Mouse","volume":"Volume 846","author":"Shea","year":"2014","journal-title":"Recent Advances in Prolactin Research"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.stemcr.2017.08.011","article-title":"Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action","volume":"9","author":"Shea","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.celrep.2019.06.098","article-title":"A Spontaneous Aggressive ER\u03b1+ Mammary Tumor Model Is Driven by Kras Activation","volume":"28","author":"Campbell","year":"2019","journal-title":"Cell Rep."},{"key":"ref_241","first-page":"820","article-title":"VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche","volume":"438","author":"Kaplan","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nm.2379","article-title":"Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs","volume":"17","author":"Oskarsson","year":"2011","journal-title":"Nat. Med."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ccell.2020.03.009","article-title":"Overcoming Endocrine Resistance in Breast Cancer","volume":"37","author":"Hanker","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13045-018-0670-9","article-title":"Molecular profiling of hormone receptor-positive, HER2-negative breast cancers from patients treated with neoadjuvant endocrine therapy in the CARMINA 02 trial (UCBG-0609)","volume":"11","author":"Liang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13058-020-01285-8","article-title":"Tumour-infiltrating lymphocytes and response to neoadjuvant letrozole in patients with early oestrogen receptor-positive breast cancer: Analysis from a nationwide phase II DBCG trial","volume":"22","author":"Skriver","year":"2020","journal-title":"Breast Cancer Res."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1158\/1078-0432.CCR-12-1000","article-title":"Molecular Profiling of Aromatase Inhibitor\u2013Treated Postmenopausal Breast Tumors Identifies Immune-Related Correlates of Resistance","volume":"19","author":"Dunbier","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1158\/1078-0432.CCR-13-1378","article-title":"Differences in the Transcriptional Response to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer","volume":"20","author":"Patani","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1158\/1078-0432.CCR-13-2602","article-title":"Effect of Aromatase Inhibition on Functional Gene Modules in Estrogen Receptor\u2013Positive Breast Cancer and Their Relationship with Antiproliferative Response","volume":"20","author":"Gao","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_249","first-page":"1","article-title":"Impact of aromatase inhibitor treatment on global gene expression and its association with antiproliferative response in ER+ breast cancer in postmenopausal patients","volume":"22","author":"Gao","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1158\/1078-0432.CCR-08-1507","article-title":"Immunomodulation of FOXP3+ Regulatory T Cells by the Aromatase Inhibitor Letrozole in Breast Cancer Patients","volume":"15","author":"Generali","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"295","DOI":"10.5301\/JBM.2012.10439","article-title":"Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients\u2014an immunohistochemical study of cd8+ and foxp3+ using double immunostaining with correlation to the pathobiological response of the patients","volume":"27","author":"Chan","year":"2012","journal-title":"Int. J. Biol. Markers"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1200\/JCO.2005.03.7432","article-title":"Endogenous steroid hormone concentrations and risk of breast cancer: Does the association vary by a woman\u2019s predicted breast cancer risk?","volume":"24","author":"Eliassen","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1186\/s13058-014-0489-4","article-title":"Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells","volume":"16","author":"Ogba","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/jnci\/djn058","article-title":"Increased Risk of Recurrence After Hormone Replacement Therapy in Breast Cancer Survivors","volume":"100","author":"Holmberg","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1001\/jama.2017.11217","article-title":"Investigators, Menopausal hormone rherapy and long-term all-cause and cause-specific mortality: The women\u2019s health initiative randomized trials","volume":"318","author":"Manson","year":"2017","journal-title":"JAMA"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1093\/jnci\/dji071","article-title":"Stockholm Breast Cancer Study, Menopausal hormone therapy after breast cancer: The Stockholm randomized trial","volume":"97","author":"Rutqvist","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.maturitas.2005.03.004","article-title":"Menopausal hormone therapy (HT) in patients with breast cancer","volume":"53","author":"Batur","year":"2006","journal-title":"Maturitas"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","article-title":"TGFbeta in Cancer","volume":"134","author":"Massague","year":"2008","journal-title":"Cell"},{"key":"ref_259","first-page":"202","article-title":"Transforming growth factor-beta in breast cancer: Too much, too late","volume":"1","author":"Akhurst","year":"2009","journal-title":"Breast Cancer Res."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/cmdc.201000146","article-title":"Jostling for Position: Optimizing Linker Location in the Design of Estrogen Receptor-Targeting PROTACs","volume":"5","author":"Cyrus","year":"2010","journal-title":"Chem. Med. Chem."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"112689","DOI":"10.1016\/j.ejmech.2020.112689","article-title":"Targeting estrogen receptor \u03b1 for degradation with PROTACs: A promising approach to overcome endocrine resistance","volume":"206","author":"Lin","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_262","first-page":"1","article-title":"Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer","volume":"11","author":"Pawlowska","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s12609-019-00333-3","article-title":"Combination Immunotherapy Strategies in Breast Cancer","volume":"11","author":"Chun","year":"2019","journal-title":"Curr. Breast Cancer Rep."},{"key":"ref_264","doi-asserted-by":"crossref","unstructured":"Singh, S., Zhang, X.H.F., and Rosen, J.M. (2020). TIME Is a Great Healer\u2014Targeting Myeloid Cells in the Tumor Immune Microenvironment to Improve Triple-Negative Breast Cancer Outcomes. Cells, 10.","DOI":"10.3390\/cells10010011"},{"key":"ref_265","doi-asserted-by":"crossref","unstructured":"Lopez-Yrigoyen, M., Cassetta, L., and Pollard, J.W. (2020). Macrophage targeting in cancer. Ann. N. Y. Acad. Sci.","DOI":"10.1111\/nyas.14377"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41423-020-0504-x","article-title":"Cancer immunotherapy with gammadelta T cells: Many paths ahead of us","volume":"17","author":"Kabelitz","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.semradonc.2019.12.008","article-title":"Priming and Propagating Anti-tumor Immunity: Focal Hypofractionated Radiation for in Situ Vaccination and Systemic Targeted Radionuclide Theranostics for Immunomodulation of Tumor Microenvironments","volume":"30","author":"Jagodinsky","year":"2020","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature23465","article-title":"CDK4\/6 inhibition triggers anti-tumour immunity","volume":"548","author":"Goel","year":"2017","journal-title":"Nature"},{"key":"ref_269","doi-asserted-by":"crossref","unstructured":"Lelliott, E.J., Kong, I.Y., Zethoven, M., Ramsbottom, K.M., Martelotto, L.G., Meyran, D., Jiang Zhu, J., Costacurta, M., Kirby, L., and Sandow, J.J. (2021). CDK4\/6 inhibition promotes anti-tumor immunity through the induction of T cell memory. Cancer Discov.","DOI":"10.1158\/2159-8290.CD-20-1554"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/15\/3725\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:34:28Z","timestamp":1760164468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/15\/3725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,24]]},"references-count":269,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cancers13153725"],"URL":"https:\/\/doi.org\/10.3390\/cancers13153725","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,24]]}}}