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. 2026 Jul 31;32:10760296261472666. doi: 10.1177/10760296261472666

Sex-specific Risks in Lung Cancer-Associated Thrombosis: Focus on Female Patients

Margaux Geier 1,2,✉, Jessica Nguyen 2, Benjamin Auberger 1,2, Renaud Descourt 1,2, Gilles Quéré 2, Chloé Ntshaykolo 3, Estelle Dhamelincourt 2, Inès Peillon 2, François Lucia 4,5, Vincent Bourbonne 4,5, Francis Couturaud 1,3
PMCID: PMC13428149  PMID: 42536807

Abstract

Sex and lung cancer-associated thrombosis (CAT) matter. Venous thromboembolism (VTE) is a frequent and serious complication in lung cancer, and accumulating evidence suggests that sex-related factors may influence thrombotic risk. In this review, we highlight the epidemiological, clinical, and biological specificities of women in relation to thrombotic risk in lung cancer. We explore sex-specific determinants of CAT, including host-, tumor- and treatment-related factors. Special attention is given to oncogene-addicted adenocarcinoma, particularly enriched in women and their implications for VTE risk and anticoagulation management. We also discuss the therapeutic challenges specific to female patients, including bleeding risks, drug–drug interactions with tyrosine kinase inhibitors and the need for sex-informed VTE risk stratification.

Keywords: venous thromboembolism, women, lung cancer, sex-specific thrombotic risk

Highlights

  • • Sex-related factors may influence venous thromboembolism (VTE) risk in lung cancer, although available evidence remains heterogeneous

  • • Women with lung cancer present distinct host-,tumor-, and treatment-related characteristics that may affect VTE management

  • • Caution is warranted when combining direct oral anti-coagulants with small-molecule inhibitors, particularly in women with oncogene-addicted NSCLC, due to bleeding risk and drug-drug interactions

  • • Sex and tumor molecular profile should be integrated into VTE risk prediction models in oncology

1. Introduction

Lung cancer remains the leading cause of cancer-related mortality worldwide, in both sexes. 1 Strikingly, more women now die from lung cancer than from any other malignancy, and its incidence continues to rise among females—especially among non-smokers. A young, non-smoking woman diagnosed with lung cancer certainly defies the stereotype.

Concurrently, lung cancer confers a fourfold increased risk of venous thromboembolism (VTE) 2 and has become the most common primary site of cancer-associated thrombosis (CAT). 3 CAT encompasses a wide range of VTE, primarily pulmonary embolism (PE) and deep vein thrombosis (DVT), 4 both of which are associated with impaired quality of life, increased early mortality 5 and significant healthcare costs.

Women with lung cancer may represent a population with dual vulnerability—oncologic and thrombotic—yet they remain underrepresented in VTE-specific analyses. In the era of precision medicine, this has renewed interest in exploring sex-specific determinants of thrombosis risk, particularly in lung cancer.

The scope of this review is to highlight specificities of VTE in lung cancer women by integrating epidemiological, biological, diagnostic, and therapeutic insights. The main sex-specific determinants of VTE discussed in this review are summarized in Table 1.

Table 1.

Sex-specific Determinants of Venous Thromboembolism in Women With Lung Cancer

Domain Female-specific features Potential impact on VTE risk Level of evidence
Epidemiology Increasing incidence of lung cancer in women; higher proportion of never-smokers; younger age at diagnosis Different baseline thrombotic risk profile Large population-based cohorts
Host-related factors Hormonal influences; body composition (lower body weight); sex-specific pharmacokinetics Modulation of coagulation, bleeding risk, and drug exposure Observational studies
Microbiome (emerging factor) Sex-related differences in gut microbiota composition; potential modulation by hormones, diet, and cancer therapies Possible influence on systemic inflammation, immune activation, and coagulation pathways Exploratory studies, indirect evidence
Tumor histology Higher prevalence of adenocarcinoma Histologic subtype associated with higher VTE risk Cohort studies
Molecular profile Enrichment in oncogene-addicted NSCLC (EGFR, ALK, ROS1, RET); KRAS mutations also reported in never-smoking women Certain drivers associated with increased VTE risk Retrospective cohorts
Tumor microenvironment Sex-specific immune landscape; higher immune checkpoint expression; estrogen-related angiogenesis Pro-inflammatory and prothrombotic tumor microenvironment Translational studies
Treatment-related factors More frequent exposure to TKIs and targeted therapies; potential drug–drug interactions with DOACs Increased thrombotic and/or bleeding risk Real-world data, clinical trials
Diagnostic challenges Atypical symptom presentation; incidental PE; limited performance of D-dimer and clinical scores in cancer Risk of delayed or missed diagnosis Observational studies
Anticoagulant management Higher bleeding risk in low body weight and premenopausal women (e.g. genital tract bleeding); limited sex-specific trial data Need for individualized anticoagulation strategy Post-hoc analyses, expert opinion
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References supporting each item are provided in the corresponding sections of the text.

1.2. Literature Search Strategy

This review was conducted as a narrative (non-systematic) review. A literature search was performed using PubMed and Embase to identify relevant articles published in English over the past two decades. Search terms included combinations of “lung cancer,” “venous thromboembolism,” “cancer-associated thrombosis,” “sex differences,” “women,” “oncogenic drivers,” and “anticoagulant therapy.” Priority was given to large observational cohorts, prospective studies, randomized clinical trials, and recent high-quality reviews addressing sex-specific aspects of lung cancer-associated thrombosis. In addition, selected retrospective studies focusing on specific molecular subgroups (e.g. oncogene-addicted non-small cell lung cancer) were included, given the relative rarity of these patient populations and the limited availability of prospective data. Additional references were identified through manual screening of bibliographies of key articles. Given the integrative and exploratory aim of this review, a formal PRISMA methodology was not applied.

2. Women and Lung Cancer: The Double Shift

Over the past two decades, epidemiological trends in lung cancer have revealed two major shifts. First, a marked shift in the sex distribution of lung cancer: the incidence of lung cancer has increased markedly in women, while remaining stable in men. In France, the proportion of female patients rose from 16% in 2000 to 34.6% in 2020, while the proportion of male patients declined from 84% to 65.4% over the same period. 6 Despite being diagnosed at a younger age (66.8 vs 68.6 years), women have a better prognosis than men: the 3-year overall survival rate reaches 45.1% versus 34.2%, and median overall survival is 29.2 months compared to 15.8 months. 7 Second, a histologic shift: adenocarcinoma, a subtype of non-small cell lung cancer (NSCLC), has become predominant in both sexes and is particularly frequent in female smokers.7,8 In parallel, the incidence of cancer with glandular differentiation is rising among individuals who never smoked,6,9 a group that is approximately 2.5 times more likely to be female.8,10 Recent epidemiological data support a higher susceptibility of women to lung cancer in the absence of active smoking. In a large married couple cohort study, Cai et al. reported that female never-smokers exhibited a significantly higher lung cancer risk than never-smoking men despite shared environmental exposures, suggesting sex-specific vulnerability beyond passive smoking alone. 11 In addition, a recent review highlights the role of sex-specific environmental and biological factors—including indoor air pollution, occupational exposures, and hormonal influences—in lung cancer development among never-smoking women, although much of the evidence derives from Asian populations. 12 Beyond their role in lung carcinogenesis, several of these sex-specific environmental exposures are also under investigation as potential modulators of thrombotic risk through chronic inflammation, endothelial dysfunction, and immune dysregulation, as suggested by large prospective cohort studies linking ambient air pollution to an increased risk of venous thromboembolism.13,14

These epidemiological observations are particularly relevant when considering CAT in lung cancer, as they underscore the intersection between histological subtype, sex, and thrombotic risk. Indeed, in a cohort study of 537 lung cancer patients, the risk of VTE was three times higher in those with adenocarcinoma compared to squamous cell carcinoma, suggesting a high-risk thrombotic potential of this histologic subtype. 15 Moreover, adenocarcinoma has been identified as an independent risk factor for PE in patients with lung cancer. 16 However, the subgroup most concerned by these findings—non-smoking women with adenocarcinoma—remains insufficiently represented in clinical research, limiting the applicability of current risk stratification tools. Moreover, this population is distinctive due to the high prevalence of targetable oncogenic drivers—some of which are associated with an increased risk of VTE—and the use of corresponding targeted therapies, which themselves may carry an intrinsic prothrombotic risk. Further details are discussed in Sections 3.2 and 3.3.

These epidemiological differences also translate into diagnostic and therapeutic challenges, particularly concerning thrombotic risk.

3. Thrombosis Risk Factors in Women With Lung Cancer

Risk assessment models such as the Khorana score are widely used to stratify VTE risk in cancer patients. 17 Five variables were selected: site of cancer, platelet and leukocyte counts, haemoglobin and/or use of erythropoiesis stimulating agents and body mass index. However, these models were developed primarily in populations undergoing chemotherapy and do not account for sex-specific factors. They have not been validated in subgroups such as never-smokers or patients treated with targeted therapies, which are frequent among women with lung adenocarcinoma. The risk of thrombosis in lung cancer is multifactorial. It can be categorized into host-related, cancer-related, and treatment-related determinants—each of which may interact with sex-specific biological or clinical features.18,19

3.1. Host-Related Factors

The relationship between female sex and VTE risk in lung cancer remains incompletely understood. While some prospective cohorts, including CANTARISK, 5 identified female sex as a potential predictor of VTE, more recent pooled analyses have reported inconsistent findings, with substantial heterogeneity across studies. 20 These discrepancies suggest that sex alone may not fully capture thrombotic risk and that interactions with tumor biology, molecular alterations, treatment exposure, and host-related factors should be considered.

To better understand the mechanisms that may contribute to thrombotic risk in women with lung cancer, hormonal factors have been explored as potential contributors to both lung carcinogenesis and thrombogenesis. Although, the association between menstrual and childbearing factors and the risk of lung cancer among women is still debated, 21 preclinical models have demonstrated cross-talk between estrogen receptors and growth factor pathways. 22 In the Women’s Health Initiative (WHI) randomized clinical trial, combined estrogen-progestin therapy in postmenopausal women did not increase lung cancer incidence but was associated with a significant rise in lung cancer–related mortality in a post-hoc analysis—possibly due to an adverse impact on NSCLC outcomes. 23 Notably, no data was provided on the occurrence and outcomes of VTE, specifically among lung cancer women treated with combined hormone therapy, leaving open questions about the potential contribution of hormone-related VTE to the poorer outcomes observed in this population.

The gut and lung microbiota have emerged as key modulators of systemic inflammation, vascular integrity, and immune homeostasis, all of which play important roles in thrombogenesis. Dysbiosis, characterized by reduced levels of Faecalibacterium and enrichment in Enterobacteriaceae, has been linked to prothrombotic states in cancer patients in recent studies.24,25 Biological sex influences microbiota composition and function, partly through sex hormones. 26 It is also suggested that the bacteria-to-human cell ratio is 1.3 in men and 2.2 in women. 27 The concept of a “microgenderome” highlights the dynamic interaction between the microbiome and hormonal status, which may contribute to sex-specific VTE susceptibility. While direct evidence in lung cancer is still limited, initial metagenomic studies suggest sex-related patterns in the gut–lung axis that could impact both tumor progression and thrombotic risk.

Additional female-specific prothrombotic pathways have been proposed but remain poorly explored in lung cancer. These include body composition and adiposity, which are associated with a pro-inflammatory state and elevated levels of prothrombotic biomarkers —although this may be less prominent in clinical thoracic oncology, where patients frequently present with weight loss. Sex-related genetic polymorphisms involving coagulation genes and/or hormonal receptors — such as variants of tissue factor (TF) pathway inhibitor, factor V Leiden, or differential expression of microRNAs related to the estrogen-coagulation axis— may also contribute. Furthermore, sex-specific environmental exposures (e.g., tobacco, air pollution, household toxins) are currently under investigation as potential contributors to thrombogenic risk.

3.2. Tumor-Related Factors

Histology and tumor stage are well-established factors influencing the risk of VTE in lung cancer. Patients with metastatic disease are at particularly high risk. Interestingly, women tend to be diagnosed at earlier stages compared to men, 28 which could act as a protective factor. However, as previously mentioned, women more frequently present with adenocarcinoma, a histologic subtype associated with a higher thrombotic potential.15,16

Inflammation, tumor biology and microenvironment (TME), along with coagulation, might exhibit different dynamics based on sex. A key biological mechanism underlying CAT is the overexpression of TF by tumor cells. Aberrant or sustained TF expression contributes to a procoagulant phenotype and is modulated by several oncogenes and tumor suppressor genes. 29 In non-squamous NSCLC, tumor biology differs significantly between sexes. 30 Molecular profiling has revealed a higher prevalence of oncogenic drivers in women and never-smokers, particularly EGFR mutations (21% in women vs. 44% in never-smokers) and HER2 mutations (1% vs. 4%), as well as ALK rearrangements (6% vs. 14%). ROS1 and RET fusions also appear more frequently in these subgroups. Some of these have been linked to altered thrombotic risk, although the associations remain incompletely understood. Preclinical studies have suggested that activation of certain oncogenes can directly upregulate the expression of haemostatic genes. 31 A prospective Chinese cohort of newly diagnosed NSCLC patients found that EGFR mutations were associated with a reduced risk of VTE, possibly through downregulation of TF expression. 32 However, other studies have reported conflicting results. A retrospective analysis by Corrales et al. 33 did not confirm a protective effect of EGFR mutations.

In contrast, ALK-positive lung cancer appears to be associated with the highest initial risk of VTE. In a retrospective cohort, Roopkumar et al. reported up to a fourfold increase in VTE risk among patients with ALK rearrangements, along with a high rate of recurrence, highlighting both the clinical impact and the complexity of thrombotic management of this subgroup. 34 In a cohort of ROS1-rearranged NSCLC, the incidence of thromboembolic events (TEEs) within ±90 days of diagnosis reached 34.7%. 35 Among the 95 patients with ROS1 alterations, 53.7% were women. Compared to EGFR and KRAS-mutated cancer, ROS-1-was associated with a higher odds of TEEs, although female sex was not independently predictive in multivariate analysis. These findings support the hypothesis that molecular characteristics may contribute more strongly to thrombotic risk than sex alone in selected NSCLC subgroups. While KRAS mutations are classically associated with smoking-related lung adenocarcinoma, recent data challenge this paradigm, especially in women. Dogan et al. showed greater susceptibility of women to KRAS-mutant cancers, even with lower tobacco exposure, particularly for KRAS G12C. 36 In the WHI cohort, Moorthi et al. identified KRAS mutations, including G12C, in never-smoking women. 37 Although less well characterized, KRAS tumors may also confer increased VTE risk, possibly via inflammation, endothelial activation, and TF expression. 38

Emerging evidence highlights significant sex-based differences in the TME of NSCLC that may influence thrombotic pathways. Transcriptomic data suggested that women exhibit a distinct immunological profile, with greater T-cell dysfunction status, higher expression of inhibitory immune checkpoint molecules, and higher abundance of immune-suppressive cells. 39 Such features may contribute to a chronically immunosuppressive and pro-inflammatory TME, which is known to be conducive to thrombogenesis. In addition, estrogen signaling may promote tumor angiogenesis and lymphangiogenesis through an estrogen receptor alpha, enhancing the prothrombotic potential of the TME. 40 Although no direct causal relationship has yet been established with CAT, these biological particularities could help explain the elevated VTE risk observed in certain subgroups of women with lung cancer.

3.3. Treatment-Related Factors

The class of therapeutic agents used can significantly impact the risk of VTE in both men and women. Historically, platinum-based doublet and cytotoxic chemotherapy regimens have constituted the cornerstone of lung cancer treatment, with varying degrees of vascular toxicity and procoagulant effects, particularly agents such as cisplatin and gemcitabine. 41 The longstanding notion that VTE risk increases during treatment remains valid. 17 Anti-angiogenesis agents such as bevacizumab have also been associated with an increased risk of thrombotic events. 42 Overall, the thrombotic risk associated with these traditional systemic treatments appears to affect men and women similarly, without significant sex-based differences reported in the literature.

Immune checkpoint inhibitors (ICIs) have become a cornerstone of treatment for advanced NSCLC. Accumulating evidence suggests that ICI exposure is associated with a higher incidence of venous thromboembolic events compared with historical cohorts treated without immunotherapy, although a direct causal relationship remains difficult to establish. Mechanistically, immune-mediated inflammation, endothelial activation, and cytokine release may contribute to a prothrombotic milieu. A recent comprehensive analysis across cancer types confirmed an increased risk of VTE in patients treated with ICIs. 43 In lung cancer, real-world studies have reported clinically relevant VTE rates in patients receiving first-line immunotherapy or chemo-immunotherapy, with VTE occurrence associated with poorer outcomes and higher PD-L1 expression.44,45 However, most studies were not designed to assess sex-specific differences, and whether women experience a differential thrombotic risk under ICIs remains unknown.

The emergence of molecular profiling has also revolutionized lung cancer management, particularly for oncogene-addicted non-squamous NSCLC, introducing new therapeutic classes with distinct safety profiles. In a retrospective cohort study, Hill et al. reported that first-line targeted therapies were associated with a higher cumulative incidence of VTE compared to chemotherapy alone, and remained independently predictive of VTE in multivariate analysis. 46 In this subgroup, more than two-thirds of patients were women, and 96.3% had adenocarcinoma. Mutation-specific data were lacking, but only 15.6% of patients were nicotine-dependent, suggesting a predominantly light or never-smoker population. Yet, data from prospective studies such as CANTARISK have suggested the opposite trend, as authors identified a significantly lower VTE risk in never-smoking patients with lung adenocarcinoma—most of whom were treated with targeted therapies rather than chemotherapy—highlighting conflicting findings between real-world and trial-based data. 5 These discrepancies may reflect differences in study design, patient selection, timing of VTE assessment, and the molecular profiles represented in each cohort. In particular, thrombotic risk may vary according to specific oncogenic drivers and treatment regimens, making direct comparisons between heterogeneous populations challenging.

More recently, amivantamab, a bispecific antibody targeting EGFR and MET, has been under investigation as monotherapy or in combination with lazertinib for EGFR mutated NSCLC. In the MARIPOSA trial, 47 TEEs occurred in 37% of patients treated with the combination, mostly within the first four months, and 2% developed recurrent VTE. While sex-specific VTE data were not disclosed, women were overrepresented in the trial (64% vs 59% in the comparator arm). The thrombotic mechanism involved is not fully understood but prophylactic anticoagulation has been consequently incorporated into ongoing clinical trials during the first four months of treatment—a relatively rare practice in oncology trials.

Finally, it is important to consider that many thrombotic events occur around the time of cancer diagnosis, potentially before treatment initiation. Targeted therapies may thus have limited influence on early thrombotic risk, as illustrated in ROS1-rearranged NSCLC. 35 Sex-specific data on thrombotic risk remain scarce in therapeutic trials, limiting our understanding of potential differences. Combining sex and molecular profiles may offer a more accurate assessment of VTE risk in patients with lung cancer.

4. Diagnostic Challenges of VTE in Lung Cancer Women

Sex-based differences have been reported in the clinical presentation of VTE, although these remain understudied in cancer patients. Using data from three large cohorts (MEGA, Hokusai-VTE, RIETE), Sheres et al. observed a higher proportion of PE in women, while DVT was predominant in men — regardless of age or provoking factors. However, cancer-specific analyses were lacking in their study. 48 The authors also suggested potential sex-related differences in VTE symptom perception: men may more often report leg pain, whereas women might notice chest symptoms earlier. Such variations could contribute to diagnostic delays or misinterpretation, particularly in oncology contexts. Indeed, sex-related diagnostic bias exists and VTE might be underdiagnosed in women. This is even more marked in the case of lung cancer. In thoracic oncology, symptoms such as dyspnea or pleuritic chest pain in women may be prematurely attributed to anxiety, especially in younger patients. This diagnostic bias can lead to underdiagnosis of PE, which is often misattributed to cancer progression or treatment-related side effects. Furthermore, lower limb edema is frequently observed in patients receiving systemic therapies (e.g., pemetrexed, MET inhibitors), potentially masking signs of DVT. Paradoxically, women—who often pay close attention to somatic changes—may normalize these symptoms due to chronic exposure to treatment-related side effects.

In addition, PE is frequently diagnosed incidentally in lung cancer patients during routine imaging performed for staging or disease assessment, often in the absence of specific symptoms. 49 This high proportion of incidental diagnoses suggests that clinical suspicion for PE is frequently low, and that symptom-driven diagnostic strategies may fail to identify thromboembolic events—particularly in women presenting with mild, atypical, or non-specific respiratory complaints.

Beyond clinical presentation, diagnostic strategies for VTE—such as D-dimer testing and clinical probability scores—have rarely been evaluated in sex-specific oncology settings. In patients with cancer, D-dimer levels are frequently elevated due to tumor-related inflammation, disease burden, or anticancer treatments, which substantially limits their negative predictive value for excluding VTE. While age-adjusted D-dimer thresholds are routinely applied, no sex-specific adaptations exist, despite evidence that women, particularly younger ones, may exhibit higher baseline D-dimer levels.50,51 Similarly, commonly used clinical pre-test probability scores incorporate cancer as a risk item, leading most oncology patients to be classified a priori as high probability and thereby reducing the discriminative performance of these algorithms. Moreover, most diagnostic algorithms were developed in cohorts with low cancer prevalence and male predominance, raising concerns about their accuracy in women with lung cancer. Altogether, these limitations may contribute to diagnostic uncertainty and potential underdiagnosis of VTE in this population.

5. Therapeutic Strategies and Outcomes

5.1. Anticoagulant Therapies in Women With Lung Cancer

Current guidelines recommend the use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute cancer-associated VTE. 52 In French recommendations, apixaban is preferentially positioned among DOAC options, 53 with no distinction between the sexes. However, sex-disparities in anticoagulant efficacy and safety remain insufficiently documented in lung cancer cohorts.

In women with lung cancer-associated thrombosis, several specific factors warrant careful consideration. First, low body weight (<50 kg), more common among female patients, particularly justifies caution when prescribing fixed-dose anticoagulant due to an increased bleeding risk. Second, as previously mentioned, women more frequently present with oncogene-addicted NSCLC and are treated with tyrosine kinase inhibitors (TKIs), which may improve prognosis but increase the risk of developing brain metastases during the course of the disease (particularly with ALK and EGFR alterations). Brain lesions heighten both thrombotic and bleeding risks, especially intracranial hemorrhage, leading some clinicians to favor LMWH over DOACs when metastases are active and unstable. Third, younger women may be at higher risk for genital tract bleeding during anticoagulation, particularly with DOACs, an adverse event that remains poorly documented in clinical trials,54-58 where sex-specific bleeding outcomes were not systematically reported.

Adherence to anticoagulation may also differ by sex, with patient preference, history of VTE, and perceptions of bleeding risk playing significant roles in treatment selection.

5.2. Interactions With Cancer Therapies

The use of DOACs should be approached with caution when combined with small-molecule inhibitors (SMIs), due to concerns about bleeding risk and potential drug–drug interactions (DDIs). 59 This is particularly relevant for women, who more frequently receive TKIs in the context of addicted NSCLC. DOACs and TKIs are both metabolized via cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), a drug-efflux pump, exposing patients to the risk of altered DOAC exposure, with either increased bleeding or reduced efficacy. While SMIs efficacy and toxicity do not seem affected, practical recommendations now include DOAC dose adjustments in these settings. Furthermore, women may require an even more anticoagulant personalized approach, due to sex-specific pharmacokinetics: they typically exhibit higher liver activity of CYP3A4, variation of body composition, and differences in liver volume and hormonal environment, all of which can impact drug metabolism and clearance. Emerging hypotheses also suggest sex-related differences in mitochondrial function that might impact drug absorption, intracellular transport, and anticoagulation effect. 60

In this context, novel therapies are under investigation. Research is now focusing on inhibition of the intrinsic pathway, with factor XI (FXI) emerging as a promising target. 61 Abelacimab, an anti-FXI monoclonal antibody, presents a “hemostasis-sparing” profile and may be especially beneficial for high-bleeding-risk patients, such as young women with mutated NSCLC and CAT. However, the management of CAT in the setting of brain metastases remains uncertain, as untreated intracranial lesions were an exclusion criterion in the pivotal ASTER trial. 62

5.3. Prognostic Impact of Thrombosis in Female Lung Cancer Patients

Across major prospective cohorts such as CARAVAGGIO (apixaban arm: 49.3% women; 18.2% with lung cancer), ADAM VTE (52% women; 21.8% lung cancer), Hokusai VTE (edoxaban arm: 43% women; 14.8% lung cancer), and SELECT-D (rivaroxaban arm: 43% women; 11% lung cancer), few studies have conducted sex-stratified analyses specifically in lung cancer subpopulations.54,56-58 Although reduced mortality has been observed in women, the long-term consequences of VTE—such as post-thrombotic syndrome—remain poorly characterized in this subgroup.

Sex-related differences in VTE outcomes have been explored in large observational cohorts. In the RIETE registry, Martín-Martos et al 63 analysed sex differences in cancer-associated VTE among 1727 lung cancer patients, including 23% of women. Female patients demonstrated a lower overall mortality risk (RR: 0.79; 95% CI: 0.70–0.92) than men. Though rates of VTE recurrence and major bleeding were numerically lower in women, the differences did not reach statistical significance.

6. Conclusion

A young, non-smoking woman with lung cancer challenges traditional clinical archetypes and underscores the need to revisit our approach to thrombosis in this population. Despite increasing awareness of sex disparities in lung cancer epidemiology, biology, and treatment response, most available data derive from mixed-sex cohorts with limited or no stratification. This underreporting of sex-specific findings limits our ability to personalize risk assessment and anticoagulation strategies. Women with lung cancer represent a distinct subset whose thrombotic risk is shaped by sex-specific host, tumor, and treatment-related factors. Integrating sex and molecular profiles into thrombotic risk models, routinely disaggregating clinical trial data by sex, and considering hormonal and metabolic factors could enhance both safety and efficacy of VTE prevention and treatment. Ultimately, a multidisciplinary approach that incorporates sex-specific biological factors could reduce inequities and improve outcomes for women with lung cancer.

Footnotes

Author Contributions: Margaux Geier conceived and wrote the manuscript. All authors reviewed and approved the final version.

Funding: The authors received no financial support for the research, authorship, and/or publication of this article.

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

ORCID iD

Margaux Geier https://orcid.org/0000-0002-4884-5825

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