Overview: Why Thrombotic Risk Matters in HR+/HER2- Breast Cancer
Venous thromboembolism (VTE) is a well-recognized complication in cancer patients, including those with hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer. While targeted endocrine therapies and CDK4/6 inhibitors have improved outcomes, they may also influence thrombosis risk through complex interactions with tumor biology, treatment regimens, and patient comorbidities. Accurate thrombotic risk assessment helps clinicians tailor preventative strategies, optimize treatment choices, and reduce morbidity and mortality associated with VTE.
Key Risk Factors to Consider
Risk for thrombosis in HR+/HER2- breast cancer is multifactorial. Clinicians should evaluate:
- Patient-related factors: age, obesity, prior VTE, inherited thrombophilia, recent surgery or immobilization, and comorbidities such as cardiovascular disease or diabetes.
- Tumor- and disease-related factors: tumor burden, stage at diagnosis, and metastatic disease presence, which can elevate hypercoagulability through cancer cell–derived procoagulants.
- Treatment-related factors: endocrine therapy (e.g., aromatase inhibitors), CDK4/6 inhibitors, targeted therapies, and chemotherapy agents can modulate platelet activity, coagulation cascades, and vascular integrity.
- Laboratory and functional markers: elevated D-dimer, reduced platelets, high C-reactive protein (CRP), or abnormal coagulation parameters may signal increased thrombosis risk, though no single test definitively predicts VTE in all patients.
Risk Assessment Tools: What to Use (and What to Know)
Several risk assessment tools have been adapted for cancer-associated thrombosis, though cancer type-specific accuracy varies. Clinicians often integrate multiple elements to guide decisions:
- Cancer-Specific Models: Some tools incorporate tumor type, stage, and therapy to estimate risk, but validation in HR+/HER2- breast cancer is ongoing.
- General VTE Scales: Tools like the Khorana score may be used with caution, recognizing limitations in breast cancer cohorts and the influence of therapies not fully captured by the score.
- Dynamic Risk Evaluation: Reassess risk during treatment, especially when adding immunotherapies, prolonged immobilization, or when new metastases emerge.
Ultimately, risk scoring should be integrated with clinical judgment and patient preferences, with particular attention to modifiable risk factors such as weight management, smoking cessation, and activity levels.
Practical Strategies to Mitigate Thrombosis Risk
For patients with HR+/HER2- breast cancer, several approaches can help reduce VTE risk while maintaining effective cancer control:
- Pharmacologic Prophylaxis: Prophylactic anticoagulation is not universally recommended for all cancer patients due to bleeding risk. In select high-risk individuals, low-dose anticoagulants may be considered after careful assessment of bleeding risk, patient preferences, and bleeding history. Shared decision-making is essential.
- Therapy Choice and Timing: When feasible, choose treatment regimens with a favorable thrombotic profile. Avoid prolonged immobilization and plan perioperative VTE prophylaxis around surgeries or invasive procedures.
- Lifestyle and Supportive Care: Encourage physical activity within tolerance, manage obesity, and optimize control of comorbidities that can amplify thrombosis risk.
- Monitoring and Reassessment: Regular follow-up to monitor symptoms of VTE (leg swelling, chest pain, dyspnea) and to reassess risk as disease and therapy evolve.
Clinical Scenarios: Applying the Risk Assessment in Practice
A clinician may encounter multiple real-world scenarios in HR+/HER2- breast cancer care:
- A patient starting a CDK4/6 inhibitor with endocrine therapy and a high BMI presents several risk factors. A shared decision about prophylactic strategies and close VTE monitoring is appropriate.
- During adjuvant chemotherapy, a patient develops inflammatory markers and an elevated D-dimer. The team weighs additional imaging, thrombosis workup, and consideration of prophylactic measures.
- With metastatic progression, treatment plans shift, potentially increasing thrombotic risk. Ongoing reassessment ensures that thrombosis prevention aligns with evolving cancer control goals.
Concluding Thoughts: Personalizing Thrombosis Risk Management
Assessing thrombotic risk in HR+/HER2- breast cancer is a nuanced process that blends evidence-based tools with individualized clinical judgment. By recognizing patient-specific risk factors, monitoring dynamic changes during therapy, and engaging patients in shared decision-making, clinicians can optimize both cancer outcomes and thrombotic safety. Ongoing research will continue to refine risk models and prophylactic strategies, ultimately improving the care trajectory for people living with this breast cancer subtype.
