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\n[https://doi.org/10.1080/2162402X.2026.2696059](https://doi.org/10.1080/2162402X.2026.2696059)  \nREVIEW ARTICLE     \nThe peripheral immune landscape of human breast cancer  \nEsmeralda García-Torralbaa, b,c,d, Aitziber Buquéa, 1 and Lorenzo Galluzzia, 1   \naCancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, United States; bDepartment of Medical Oncology, Hospital Universitario Morales Meseguer, Murcia, Spain; cDepartment of Medicine, Medical School, University of Murcia, Murcia, Spain; dIMIB-Arrixaca, Murcia, Spain  \nABSTRACT  \nThe clinical management of patients with breast cancer is largely dictated by tumor stage, disease subtype and (at least in some settings) specific molecular features thereof (e.g., BRCA1 mutations, PD-L1 positivity) . However, not all patients with breast cancer respond to therapeutic approaches that a priori are precisely targeted to their disease. At least in part, this may reflect the fact that breast neoplasms are highly heterogeneous from a broad immunological perspective, even when they exhibit similar disease subtype and molecular features. Thus, integrating extra immunological parameters into current decision-making algorithms may considerably improve clinical management in this large patient population. In this context, circulating indicators of global immune fitness and ongoing anticancer immunity stand out as particularly promising tools for minimally invasive prognostic and/or predictive assessments. Here, we summarize and critically discuss the circulating immune landscape of human breast cancer, whenever possible comparing across disease subtypes, stages, and treatment outcomes.  \nARTICLE HISTORY  \nReceived 7 May 2026 Revised 23 June 2026 Accepted 24 June 2026  \nKEYWORDS  \nCD8+ cytotoxic T lymphocytes; CDK4/6 inhibitors; IL6; immune checkpoint inhibitors; TGF-β; tumor microenvironment  \nIntroduction  \nBreast cancer remains a major global health burden, with an estimated 2.3 million new diagnoses and more than 650,000 deaths reported worldwide in 2022.1,2 Thus, despite substantial progress in screening, classification and treatment,3-6 the current clinical management of breast cancer remains suboptimal, calling for the urgent development of more effective strategies to control this deadly disease.  \nAs it stands, disease stage (i.e., tumor size, lymph node involvement and distant dissemination), subtype and patient-related factors are the major determinants of clinical decision making in patients with breast cancer.7,8 More specifically, early-stage disease is generally managed by a locoregional approach involving surgery with appropriate axillary staging and radiotherapy that—when indicated—is integrated with systemic interventions. The latter may be administered either before surgery (neoadjuvant therapy) or after it (adjuvant therapy) . Conversely, unresectable (locally advanced) and metastatic breast cancers are primarily managed with systemic therapy, locoregional approaches being reserved for selected clinical indications.7,8  \nDisease subtype has a major influence on such a systemic therapeutic component. Thus, breast cancers expressing hormone receptors (HRs) such as estrogen receptor 1 (ESR1, best known as ER) and/or progesterone receptor (PGR, best known as PR), but not erb-b2 receptor tyrosine kinase 2 (ERBB2, best known as HER2), are most often treated with endocrine therapy (ET) alone or combined with CDK4/  \n6 inhibitors (when locally advanced or metastatic) .9 Conversely, patients with HER2+ tumors generally receive HER2-specific agents, including modern HER2-targeted antibody-drug conjugates, 10 whereas women with triple-negative breast cancer (TNBC) are most often treated with aggressive, taxane-based chemotherapy or (in selected cases, see below) immune checkpoint inhibitors (ICIs) . 11  \nCONTACT Aitziber Buqué  [abuquemartinez@gmail.com](abuquemartinez@gmail.com)  Cancer Signaling and ","cbCaigIwcamWwOds","https://ap.wps.com/l/cbCaigIwcamWwOds","pdf",761866,14,"English","# Introduction\n## Disease stage, subtype, and treatment decisions\n## Systemic therapy by receptor status\n## Additional clinicopathological and molecular factors\n# Circulating immune landscape and clinical utility","[{\"question\":\"Why is breast cancer clinical management not fully effective despite targeted molecular features?\",\"answer\":\"Because breast tumors are highly heterogeneous immunologically, so therapies targeted to similar subtype and molecular markers do not guarantee the same response across patients.\"},{\"question\":\"What role do circulating immune indicators play in breast cancer assessment?\",\"answer\":\"Circulating indicators reflecting global immune fitness and ongoing anticancer immunity are highlighted as promising tools for minimally invasive prognostic and predictive evaluation.\"},{\"question\":\"How does disease subtype influence systemic treatment choices?\",\"answer\":\"Hormone-receptor positive tumors are treated with endocrine therapy ± CDK4/6 inhibitors, HER2+ tumors receive HER2-specific agents, and triple-negative breast cancer is commonly treated with taxane-based chemotherapy or, in selected cases, immune checkpoint inhibitors.\"}]","The peripheral immune landscape of human breast cancer | PDF",1790058834,35]