D-Dimer Dynamics as a Prognostic and Monitoring Biomarker in Triple-Negative and Metastatic Breast Cancer: A Narrative Review

Abstract

Background

Triple-negative breast cancer (TNBC) and metastatic breast cancer (MBC) remain clinically challenging because of aggressive biology, therapeutic resistance, metastatic dissemination, and substantial heterogeneity. D-dimer, a fibrin-degradation product, may capture systemic coagulation and fibrinolytic activation associated with tumour progression and cancer-associated thrombosis.

Objective

This narrative review critically examines D-dimer dynamics as a complementary biomarker for prognostic stratification, treatment monitoring, thrombotic risk assessment, and personalized care in TNBC and MBC.

Results

Evidence linking D-dimer with tumour burden, metastasis, survival, inflammation, endothelial activation, platelet–tumour interactions, and venous thromboembolism is synthesized. Particular emphasis is placed on longitudinal trajectories, including declining, stable, persistently elevated, and progressively increasing D-dimer patterns, and their potential interpretation alongside imaging, clinical status, inflammatory markers, circulating tumour DNA, and treatment exposure. Major limitations include assay heterogeneity, differences between fibrinogen-equivalent units and D-dimer units, variable reference ranges and cut-offs, and confounding by age, infection, surgery, renal or hepatic dysfunction, immobility, prior thrombosis, and anticancer treatment. Most available evidence remains observational and therefore establishes association rather than causality or proven clinical utility.

Conclusion

D-dimer dynamics represent a promising, accessible component of multimodal precision oncology, but should not independently diagnose progression, select anticancer therapy, or determine anticoagulation. Prospective multicentre studies are needed to standardize assays, validate trajectory-based thresholds, integrate D-dimer with multi-omics and artificial intelligence, and determine whether D-dimer-guided monitoring improves outcomes, particularly in resource-constrained settings and diverse African oncology populations globally appropriately.

Introduction

Breast cancer remains a major global health challenge, with substantial heterogeneity in tumour biology, metastatic behaviour, treatment response, and survival. Triple-negative breast cancer (TNBC), characterized by the absence of oestrogen receptor, progesterone receptor, and HER2 expression, is particularly challenging because of its aggressive phenotype, early recurrence, visceral and central nervous system dissemination, and historically limited targeted treatment options. Although immunotherapy, antibody–drug conjugates, poly(ADP-ribose) polymerase (PARP) inhibitors, and other molecularly informed approaches have expanded therapeutic opportunities, treatment resistance and disease progression remain important clinical problems. Metastatic breast cancer (MBC) likewise represents a biologically dynamic and generally incurable condition in which treatment aims to prolong survival, control disease, preserve quality of life, and minimize treatment-related morbidity. These challenges underscore the need for biomarkers that capture both tumour behaviour and the evolving host response to malignancy.^1,2 Coagulation activation is increasingly recognized as an important component of the cancer phenotype rather than merely a complication of advanced disease. Malignant cells can express tissue factor, release procoagulant extracellular vesicles, activate platelets and endothelial cells, and stimulate inflammatory pathways that promote thrombin generation and fibrin deposition. In turn, thrombin, platelets, fibrin, and coagulation-associated inflammatory signalling may facilitate tumour-cell survival, angiogenesis, vascular adhesion, immune evasion, and metastatic dissemination. This reciprocal relationship between malignancy and haemostasis has contributed to the concept of cancer-associated thromboinflammation, linking tumour progression with systemic coagulation and inflammatory responses.^3,4

D-dimer provides a clinically accessible measure of fibrin turnover. It is generated when plasmin degrades factor XIIIa-cross-linked fibrin and therefore reflects preceding fibrin formation and subsequent fibrinolysis. Elevated D-dimer concentrations have been associated with advanced cancer, metastatic disease, venous thromboembolism (VTE), inflammation, and adverse outcomes in several malignancies, including breast cancer. However, D-dimer is not tumour-specific. Its concentration may also increase with age, infection, inflammation, recent surgery, trauma, pregnancy, immobility, renal or hepatic dysfunction, hospitalization, prior VTE, and anticancer treatment. Consequently, an elevated value cannot by itself distinguish tumour progression from other causes of systemic coagulation activation.^5,6 An additional challenge is analytical heterogeneity. D-dimer is measured using different platforms, including enzyme-linked immunosorbent assays, immunoturbidimetric methods, and latex-based assays. Results may be reported as fibrinogen-equivalent units (FEU) or D-dimer units (DDU), with different reference intervals and clinical thresholds. Therefore, numerical cut-offs derived from one assay or population cannot automatically be extrapolated to another. This limitation is particularly important when considering D-dimer as a precision oncology biomarker, because reproducible interpretation requires assay harmonization, standardized reporting, and prospectively validated thresholds.^7,8 The central premise of this review is therefore that D-dimer dynamics may be more informative than an isolated D-dimer measurement. A persistently elevated or progressively increasing concentration may indicate sustained thromboinflammatory activity, whereas a decline during effective treatment may reflect resolution of systemic coagulation activation. Nevertheless, dynamic changes are also influenced by treatment, infection, thrombosis, inflammation, and other clinical events. Their interpretation must consequently remain integrated with disease status rather than being regarded as a direct surrogate of tumour burden.^9,10

This dynamic perspective is particularly relevant to TNBC and MBC. Aggressive tumour growth, tissue injury, hypoxia, abnormal angiogenesis, endothelial dysfunction, platelet activation, extracellular vesicle release, and immune–coagulation interactions may collectively increase fibrin turnover. In metastatic disease, additional factors—including metastatic burden, reduced mobility, central venous access, systemic therapy, hospitalization, and established or occult VTE—can further modify D-dimer concentrations. Thus, longitudinal D-dimer assessment may potentially provide complementary information about both tumour-associated thromboinflammation and cancer-associated thrombosis, provided that important confounders are systematically considered.¹¹ Accordingly, this narrative review critically examines the biological rationale, prognostic evidence, clinical limitations, and translational potential of D-dimer dynamics in TNBC and MBC. Particular emphasis is placed on serial trajectories, assay standardization, confounding, treatment monitoring, VTE risk, and integration with imaging and molecular biomarkers. The review also distinguishes established associations from emerging hypotheses and proposes a precision oncology framework in which D-dimer functions as a complementary rather than stand-alone biomarker.

Aim

The aim of this review is to critically examine the dynamics of D-dimers in triple-negative and metastatic breast cancers, elucidating their pathophysiological basis, mechanistic links to tumor progression, and clinical significance. The review seeks to synthesize current evidence on their prognostic value, explore their potential role in guiding precision care, and highlight future directions for integrating D-dimer assessment into personalized management strategies for aggressive breast cancer subtypes.

Methods

This narrative review was conducted to provide a comprehensive synthesis of current evidence on D-dimer dynamics in triple-negative and metastatic breast cancer. A systematic search of the literature was performed across multiple electronic databases, including PubMed, Scopus, Web of Science, and Embase, covering publications from January 2000 to December 2025. The search strategy combined keywords and Medical Subject Headings (MeSH) terms such as “D-dimers”, “fibrin degradation products”, “triple-negative breast cancer”, “metastatic breast cancer”, “prognosis”, and “precision oncology”. Inclusion criteria comprised original research articles, clinical cohort studies, case-control studies, prospective and retrospective observational studies, and relevant mechanistic studies investigating D-dimers in TNBC or metastatic breast cancer. Reviews, meta-analyses, and expert opinion articles were also considered to provide contextual insights. Articles not published in English or lacking full-text access were excluded. Data extraction focused on patient characteristics, study design, D-dimer assay methodology, baseline and longitudinal D-dimer levels, correlations with tumor burden, metastasis, survival outcomes, and implications for clinical care. Mechanistic studies examining the interaction between coagulation, inflammation, tumor biology, and D-dimer generation were also reviewed. The collected evidence was synthesized narratively to provide an integrated understanding of the pathophysiological mechanisms, clinical relevance, and translational potential of D-dimer measurement in aggressive breast cancer. Emphasis was placed on linking mechanistic insights to prognostic utility and precision care strategies.

Physiological and Pathophysiological Basis

D-dimers are fibrin degradation products generated through the enzymatic breakdown of cross-linked fibrin by plasmin during fibrinolysis. Under normal physiological conditions, they reflect the balanced interplay between coagulation and fibrinolysis, ensuring hemostatic stability and vascular integrity. When vascular injury occurs, the coagulation cascade is activated, culminating in thrombin-mediated conversion of fibrinogen to fibrin, which stabilizes the forming clot. Subsequently, the fibrinolytic system, primarily through plasmin activity, degrades fibrin to prevent excessive clot propagation, generating D-dimers in the process. Circulating D-dimer levels thus serve as a sensitive biomarker of ongoing coagulation and fibrinolytic activity.^12,13 In the context of cancer, this finely tuned hemostatic equilibrium is frequently disrupted, leading to a hypercoagulable state. Tumor cells, particularly those in TNBC and metastatic breast cancer, actively engage the coagulation system through multiple mechanisms. One key driver is tumor expression of procoagulant molecules, such as tissue factor (TF) and cancer procoagulant, which initiate thrombin generation and fibrin formation. TF overexpression has been consistently observed in aggressive breast cancer phenotypes, correlating with tumor invasiveness, angiogenesis, and metastatic potential.^14,15

Inflammatory mediators further amplify coagulation in cancer. Pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF), are upregulated in the tumor microenvironment. These mediators promote endothelial activation, increase vascular permeability, and upregulate TF expression on both tumor cells and host endothelial cells. The resulting pro-thrombotic milieu contributes to fibrin deposition locally within the tumor stroma and systemically in the circulation, thereby elevating circulating D-dimer levels.^16,17 Another critical component is the interaction between platelets and circulating tumor cells (CTCs). Platelets adhere to tumor cells, forming protective microthrombi that shield them from immune surveillance and facilitate their transit through the bloodstream. This platelet-tumor crosstalk not only supports metastatic dissemination but also contributes to ongoing fibrin formation and D-dimer generation. Elevated D-dimers, therefore, may reflect both systemic hypercoagulability and active metastatic processes.^18,19

Fibrin deposition within the tumor microenvironment further enhances tumor aggressiveness. Fibrin matrices provide a structural scaffold for tumor cell adhesion, migration, and invasion, while simultaneously promoting angiogenesis and local immune evasion. This creates a self-perpetuating cycle in which tumor growth and metastasis sustain hypercoagulability, leading to continuous fibrin turnover and D-dimer release.²⁰ In metastatic breast cancer, these pathophysiological mechanisms are magnified. Disseminated tumor cells interact with vascular beds in distant organs, where local thrombin generation and fibrin deposition facilitate metastatic seeding. Consequently, elevated D-dimer levels in metastatic disease reflect both tumor burden and the ongoing thrombo-inflammatory interactions that support metastatic colonization (Table 1).^21,22

Table 1.

Physiological and Pathophysiological Basis of D-Dimer Dynamics in TNBC and Metastatic Breast Cancer

Category	Physiological Role	Pathophysiological Mechanism in TNBC and MBC	Clinical Implication
Coagulation Activation	Fibrin formation for hemostasis	Tumor cells express tissue factor (TF) and release procoagulant microparticles, initiating thrombin formation and fibrin deposition	Elevated D-dimers reflect ongoing tumor-driven hypercoagulability
Fibrinolysis	Degradation of fibrin to maintain vascular patency	Continuous fibrin turnover via plasmin-mediated degradation releases D-dimers	Serves as a measurable biomarker of thrombo-inflammatory activity
Systemic Inflammation	Localized immune response to injury or infection	Cytokines (IL-6, TNF-α, IL-1β) upregulate TF, activate endothelial cells, and sustain procoagulant states	D-dimers integrate inflammatory and coagulation activity, reflecting tumor aggressiveness
Endothelial Dysfunction	Maintains vascular barrier integrity and regulates permeability	Tumor-derived factors disrupt endothelial function, increasing permeability and promoting microthrombosis	Facilitates metastatic intravasation/extravasation; D-dimers indicate endothelial involvement
Metastatic Facilitation	Limited physiologic cell trafficking	Fibrin scaffolds protect circulating tumor cells and promote adhesion to distant tissues	D-dimer elevation reflects metastatic potential and tumor burden
Neutrophil Extracellular Traps (NETs)	Trap pathogens and aid immune defense	NETs form fibrin-rich matrices that support tumor cell survival and pre-metastatic niche formation	Contributes to thrombo-inflammatory signature measured by D-dimers
Angiogenesis and Vascular Remodeling	New vessel formation in tissue repair	Tumor-secreted VEGF and thrombin signaling drive pathological angiogenesis	D-dimer elevation reflects fibrin remodeling associated with angiogenesis and metastatic colonization

Clinical Evidence and Prognostic Implications

Over the past decade, a growing body of clinical evidence has established D-dimers as a significant biomarker in breast cancer, particularly in aggressive subtypes such as TNBC and MBC. Observational studies, prospective cohorts, and retrospective analyses consistently demonstrate that elevated D-dimer levels correlate with tumor aggressiveness, metastatic potential, and adverse patient outcomes.^23–25 In TNBC, elevated baseline D-dimer levels have been associated with larger primary tumors, higher histological grades, and increased lymph node involvement. For instance, multiple studies report that TNBC patients with high D-dimer levels at diagnosis exhibit significantly shorter disease-free survival (DFS) and overall survival (OS) compared to those with lower levels. This association is thought to reflect the pro-thrombotic and inflammatory milieu characteristic of TNBC, in which fibrin deposition and systemic hypercoagulability contribute to tumor progression and early metastasis.¹¹ In metastatic breast cancer, D-dimer levels appear to mirror disease burden and progression. Elevated D-dimers frequently correlate with the extent of metastatic involvement, including visceral and skeletal metastases. Longitudinal studies indicate that rising D-dimer levels during follow-up may precede radiologic evidence of disease progression, suggesting their utility as an early indicator of relapse. Conversely, patients whose D-dimer levels normalize following systemic therapy often demonstrate better clinical outcomes, underscoring the potential of D-dimers as a dynamic biomarker for treatment response.²⁶ Beyond prognostication, D-dimers may also inform therapeutic decisions. Elevated pre-treatment D-dimer levels have been linked to increased thromboembolic risk, which is particularly relevant in TNBC and MBC where hypercoagulability is pronounced. Monitoring D-dimers can therefore guide prophylactic or therapeutic anticoagulation strategies, potentially reducing cancer-associated thrombotic complications without compromising oncologic outcomes.²⁷

Several meta-analyses have reinforced the prognostic significance of D-dimers across breast cancer populations. Collectively, these studies demonstrate that patients with elevated D-dimers have approximately 2–3 times higher risk of disease recurrence and mortality compared to those with lower levels. Importantly, D-dimers appear to provide independent prognostic information beyond conventional clinicopathologic factors, such as tumor size, nodal status, and histological grade, highlighting their potential role as a complementary biomarker in risk stratification models.²⁸ Nevertheless, the cumulative evidence supports the integration of D-dimer assessment into precision oncology strategies for TNBC and MBC. Serial monitoring of D-dimer levels can provide real-time insights into tumor progression, therapeutic efficacy, and thromboembolic risk, enabling clinicians to tailor interventions more accurately. As such, D-dimers represent not only a prognostic marker but also a potential guide for personalized management in aggressive breast cancer (Table 2).²⁹

Table 2.

Clinical Evidence and Prognostic Implications of D-Dimer Dynamics in Triple-Negative and Metastatic Breast Cancer

Clinical Setting/D-Dimer Pattern	Principal Clinical Evidence	Prognostic/Clinical Implication	Key Limitation
Newly diagnosed breast cancer – elevated baseline D-dimer	Higher concentrations are frequently associated with advanced stage, tumour burden and systemic coagulation activation.	May identify patients with a higher-risk phenotype.	Strongly influenced by age, inflammation, comorbidity and assay-specific thresholds.
TNBC – elevated D-dimer	Aggressive disease may be accompanied by enhanced coagulation, fibrin turnover and thromboinflammation.	Potential marker of adverse biology and increased thrombotic risk.	TNBC-specific prospective validation remains limited.
MBC – persistently elevated D-dimer	Persistent elevation has been associated with advanced disease and poorer clinical outcomes in observational cohorts.	May identify patients requiring intensified clinical and thrombotic surveillance.	Cannot independently distinguish tumour progression from VTE or systemic illness.
D-dimer decreasing during treatment	Declining concentrations may accompany reduction in systemic coagulation activation during clinical response.	Potential complementary indicator of favourable treatment trajectory.	Not validated as a surrogate endpoint for treatment response.
D-dimer persistently elevated despite therapy	May reflect continued tumour-associated thromboinflammation or another ongoing coagulation stimulus.	Signals need for integrated reassessment of disease, VTE, infection and treatment effects.	Nonspecific; causal relationship with treatment resistance is unproven.
Progressively rising D-dimer	Sustained increases may accompany disease progression or emerging thrombotic complications.	Potential early warning signal warranting clinical and radiological reassessment.	Optimal rate/change threshold remains undefined.
Marked rise with new symptoms	Acute elevation with dyspnoea, chest pain or limb swelling increases concern for VTE.	Supports urgent clinical evaluation for thromboembolism.	D-dimer alone is insufficient for VTE diagnosis in cancer.
D-dimer + inflammatory/haemostatic biomarkers	Combination with platelets, fibrinogen, CRP or NLR may better characterize systemic thromboinflammation.	Potentially improves multidimensional risk stratification.	Composite models require prospective validation.
D-dimer + ctDNA/imaging	Host haemostatic dynamics may complement tumour-derived molecular and radiological measures.	Promising framework for multimodal precision monitoring.	Currently investigational; clinical utility remains unproven.
Assay-specific D-dimer thresholds	FEU/DDU reporting and analytical platforms vary substantially between studies.	Standardization is essential before universal thresholds can be proposed.	Cross-study comparisons and threshold transferability remain problematic.

Abbreviations: CRP, C-reactive protein; ctDNA, circulating tumour DNA; DDU, D-dimer units; FEU, fibrinogen-equivalent units; MBC, metastatic breast cancer; NLR, neutrophil-to-lymphocyte ratio; TNBC, triple-negative breast cancer; VTE, venous thromboembolism.

Mechanistic Insights

The elevation of D-dimers in TNBC and MBC is not merely a byproduct of systemic hypercoagulability but reflects a complex interplay of tumor biology, host response, and thrombo-inflammatory signaling. Understanding these mechanisms provides insight into why D-dimers serve as reliable indicators of tumor aggressiveness and metastatic potential.^30,31 Cancer cells, particularly those in TNBC, often exhibit high expression of procoagulant molecules, most notably tissue factor (TF) and cancer procoagulant. TF initiates the extrinsic coagulation cascade, resulting in thrombin generation and the formation of fibrin networks. These fibrin matrices not only stabilize microthrombi but also provide structural scaffolds that facilitate tumor cell adhesion, migration, and invasion. As fibrin is degraded by plasmin, D-dimers are released into circulation, directly linking tumor-induced coagulation activity to measurable biomarker levels.^32,33

CTCs in aggressive breast cancers interact with platelets, forming tumor-platelet aggregates that serve multiple functions. Platelets protect tumor cells from shear stress and immune-mediated destruction in the bloodstream, promoting survival during transit to distant organs. They also release pro-angiogenic and pro-inflammatory factors, including VEGF and platelet-derived growth factor (PDGF), which support metastatic colonization. The fibrin-platelet interactions that stabilize these aggregates contribute to ongoing fibrin turnover, further elevating D-dimer levels.^34,35 Chronic inflammation within the tumor microenvironment is a critical driver of coagulation activation. Cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) upregulate TF expression on both tumor and endothelial cells, amplifying thrombin generation. In parallel, inflammatory signaling recruits immune cells that release additional proteases and reactive oxygen species, promoting fibrin deposition and degradation. This reciprocal interaction between coagulation and inflammation creates a self-perpetuating cycle that sustains elevated D-dimer levels.^36,37 D-dimers also reflect the mechanistic processes underlying metastatic dissemination. As tumor cells extravasate into distant tissues, local fibrin deposition facilitates their adhesion and colonization. Microthrombi provide a provisional matrix that supports tumor cell engraftment and shields them from host immune surveillance. Elevated D-dimers in the circulation serve as a surrogate for this ongoing metastatic activity, correlating with tumor burden and disease progression.³⁸ Fibrin matrices within the tumor microenvironment enhance angiogenesis by providing scaffolds for endothelial cell migration and growth factor localization. This promotes tumor perfusion and nutrient supply, enabling rapid proliferation and invasion. Plasmin-mediated fibrin degradation, which generates D-dimers, is integral to remodeling these matrices, linking D-dimer elevation to active tumor growth and vascular remodeling.³⁹

D-Dimer Assay Heterogeneity and Standardization

A major barrier to translating D-dimer dynamics into precision oncology is substantial analytical and reporting heterogeneity among D-dimer assays. D-dimer is measured using different platforms, including enzyme-linked immunosorbent assays (ELISA), immunoturbidimetric assays, and latex-based methods, with differences in antibody specificity, calibration, analytical sensitivity, and reporting units. Results may be expressed as fibrinogen-equivalent units (FEU) or D-dimer units (DDU), which are not directly interchangeable. Consequently, identical numerical concentrations may have different clinical meanings across laboratories, and published prognostic thresholds in breast cancer cannot be universally transferred between studies or clinical settings. This heterogeneity is particularly important when interpreting serial D-dimer measurements. Longitudinal monitoring should ideally use the same validated analytical platform, reporting unit, reference interval, and standardized blood-collection conditions. Interpretation should also account for age, recent surgery, infection or systemic inflammation, renal dysfunction, pregnancy, immobility, hospitalization, and previous or active venous thromboembolism, all of which can independently elevate D-dimer. Thus, an isolated increase should not automatically be interpreted as tumor progression or treatment failure. For precision oncology, future studies should establish assay-specific and clinically validated thresholds, harmonize FEU/DDU reporting, standardize sampling intervals, and evaluate absolute values alongside intra-individual changes or trajectories. Prospective multicenter studies using predefined analytical protocols are needed to determine whether standardized D-dimer dynamics provide incremental prognostic or monitoring value beyond established clinicopathological, imaging, inflammatory, and molecular biomarkers. Until such harmonization is achieved, D-dimer should be regarded as a context-dependent adjunctive biomarker rather than a standalone precision-treatment decision tool.^37–39

Limitations of Current Evidence

Several limitations constrain the clinical translation of D-dimer dynamics in triple-negative and metastatic breast cancer. First, the available evidence is predominantly observational and retrospective, limiting causal inference and creating potential for selection, information, and residual confounding. Second, D-dimer is a nonspecific marker of fibrin turnover and may be elevated because of age, infection, inflammation, renal dysfunction, recent surgery, immobility, or venous thromboembolism, making tumor-specific interpretation difficult. Third, substantial assay heterogeneity exists, including differences in analytical platforms, calibration, reporting units (FEU versus DDU), reference intervals, and prognostic cut-offs. This limits direct comparison across studies and prevents establishment of a universal threshold. Additional heterogeneity arises from differences in breast cancer subtype, disease stage, treatment exposure, timing of blood collection, follow-up duration, and clinical endpoints. Evidence specifically addressing serial D-dimer trajectories in TNBC and metastatic breast cancer remains limited, and most studies evaluate baseline concentrations rather than longitudinal changes. Furthermore, statistical associations reported after multivariable adjustment do not necessarily demonstrate clinically meaningful incremental predictive value. Importantly, there is currently insufficient interventional evidence demonstrating that D-dimer-guided management improves survival, treatment response, or patient outcomes. Future prospective multicenter studies should therefore standardize assays and sampling protocols, prespecify clinically relevant thresholds, account for major confounders, and determine whether dynamic D-dimer measurements provide incremental value beyond established clinical, imaging, inflammatory, and molecular biomarkers. These limitations should be addressed before routine implementation of D-dimer-guided precision care.

Conclusion

D-dimer dynamics provide a promising but not yet clinically validated approach for addressing the prognostic and monitoring challenges of triple-negative and metastatic breast cancer. Rather than relying on a single measurement, serial D-dimer trajectories may capture evolving coagulation activation, thrombotic burden, systemic inflammation, and disease progression, potentially complementing conventional clinicopathological and imaging assessments. However, D-dimer is biologically nonspecific, and its interpretation is substantially influenced by assay methodology, reporting units, reference ranges, comorbidities, treatment-related factors, and venous thromboembolism. The current evidence remains predominantly observational and correlative, with considerable heterogeneity in populations, cut-offs, sampling intervals, and analytical platforms. Therefore, D-dimer should not currently be used as a standalone biomarker to guide anticancer treatment decisions. Its greatest future value may arise from integration of longitudinal D-dimer data with clinical characteristics, imaging, inflammatory and hematologic biomarkers, molecular/multi-omics profiles, and artificial intelligence-based predictive models. Such multimodal approaches could enable dynamic risk stratification and more individualized surveillance and treatment monitoring. Prospective, multicenter studies using standardized assays, predefined thresholds, harmonized sampling protocols, and clinically meaningful endpoints are essential to establish whether D-dimer dynamics provide incremental predictive value beyond established biomarkers. Until such evidence is available, D-dimer should be considered a low-cost, accessible adjunctive biomarker with translational potential, particularly valuable where resource constraints limit access to more complex precision-oncology technologies.

Funding Statement

No fund was received to write this review paper.

Abbreviations

CRP, C-Reactive Protein; CTC, Circulating Tumor Cell; D-dimer, Fibrin Degradation Product; IL-1β, Interleukin-1 Beta; IL-6, Interleukin 6; MBC, Metastatic Breast Cancer; NETs, Neutrophil Extracellular Traps; TNBC, Triple-Negative Breast Cancer; TNF-α, Tumor Necrosis Factor Alpha; TF, Tissue Factor; VEGF, Vascular Endothelial Growth Factor.

Disclosure

The author declares no conflict of interest.