Overview
Breast cancer remains the most commonly diagnosed cancer worldwide, with the estrogen receptor–positive, HER2-negative (HR+/HER2−) subtype accounting for a large portion of cases. When breast cancer recurs, patients may face an elevated risk of thromboembolic events (TEEs), including deep vein thrombosis and pulmonary embolism. Understanding and assessing this thrombotic risk is crucial for guiding treatment decisions, balancing cancer control with patient safety, and improving outcomes.
Why thrombotic risk matters in HR+/HER2− recurrence
Thrombosis is not only a complication that can prolong hospitalization and complicate therapy, but it can also influence the choice and timing of systemic treatments such as endocrine therapy, chemotherapy, or targeted agents. In HR+/HER2− disease, tumor biology, prior therapies, and comorbidities collectively shape the risk profile. Accurate risk assessment helps clinicians identify patients who may benefit from preventive strategies and closer monitoring during recurrence management.
Key risk factors to consider
Several patient- and disease-related factors have been linked to higher thrombotic risk in recurrent breast cancer:
- Active or progressive disease with high tumor burden
- Advanced age and comorbidities (obesity, cardiovascular disease, prior VTE)
- Prior venous thromboembolism (VTE) or thrombophilia
- Immobility or reduced functional status during treatment
- Cancer-directed therapies that influence coagulation, such as certain chemotherapies or anti-angiogenic agents
- Laboratory markers suggesting hypercoagulability, including D-dimer elevations
Risk assessment tools and approach
Clinicians commonly combine general cancer-associated risk assessment with breast-cancer–specific insights. Useful elements include:
- <strongCancer-associated risk models: While no single tool perfectly predicts VTE in all cancer populations, models like the Khorana score are used to estimate baseline risk in patients starting systemic therapy. In recurrence, modified or tumor-type–specific risk assessments may offer improved performance.
- <strongLaboratory indicators: D-dimer and other coagulation markers can reflect ongoing hypercoagulability, especially in active disease or during cytotoxic treatment. Serial measurements may help track changing risk.
- <strongClinical factors: Performance status, tumor burden on imaging, and ongoing therapies inform dynamic risk appraisal.
- <strongImaging considerations: When symptoms suggest VTE, prompt diagnostic imaging (compression ultrasound for leg symptoms, CTPA for suspected PE) is essential, given the potentially subtle presentation in some patients.
Given the limitations of generic tools, many clinicians tailor risk assessment to the individual, integrating patient preferences, bleeding risk, and planned treatment regimens. Multidisciplinary discussion is often valuable to align anticoagulation decisions with oncologic goals.
Management implications
Risk stratification informs both prevention and treatment. Practical considerations include:
- <strongProphylaxis decisions: Routine VTE prophylaxis is not universally recommended for all patients with HR+/HER2− recurrence, but high-risk individuals may benefit from pharmacologic prophylaxis under specialist supervision, particularly during high-risk periods (e.g., active chemotherapy, immobilization).
- <strongAnticoagulation choices: When VTE risk is high or VTE occurs, clinicians select anticoagulants based on bleeding risk, drug interactions, renal function, and cancer-related considerations. Direct oral anticoagulants (DOACs) are increasingly used in cancer-associated VTE, but selectivity and contraindications must be evaluated.
- <strongTherapy timing and sequencing: The presence of thrombosis can influence timing of surgery, metastasis-directed therapy, or systemic endocrine therapy. Collaborative planning helps minimize delays in cancer control while safeguarding patients from bleeding or thrombotic events.
<h2 Practical guidance for clinicians
To optimize thrombotic risk management in HR+/HER2− recurrence, consider the following steps:
- Assess VTE risk at baseline and monitor dynamically during recurrence treatment.
- Evaluate bleeding risk before initiating or continuing anticoagulation, especially in patients with brain metastases or recent surgery.
- Involve patients in shared decision-making, explaining risks and benefits of prophylaxis or treatment changes in the context of cancer control.
- Coordinate care with hematology, oncology, and palliative teams to tailor strategies to patient goals and prognosis.
<h2 Future directions
Ongoing research aims to refine risk scores for HR+/HER2− recurrence, validate biomarker panels, and optimize the balance between thrombosis prevention and bleeding risk. Personalized approaches that integrate tumor biology, treatment exposure, and patient factors hold promise for safer, more effective care.
