Lymphatic research and biology · 2026
Identifying Genetic Predisposition and Clinical Risk Factors for Breast Cancer-Related Lymphedema: Toward Personalized Prevention.
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Putri Rizky Ifandriani, Sutandyo Noorwati, Siregar Nurjati Chairani, Wanandi Septelia Inawati, Harimurti Kuntjoro, Hernowo Bethy S, Brahma Bayu, Perdana Adhitya Bayu, Widiasti Innas, Sari Erin Kurnia, Panigoro Sonar Soni
Аннотация
BACKGROUND: Breast cancer-related lymphedema (BCRL) remains a major chronic complication following axillary lymph node dissection (ALND), particularly in regions where locally advanced breast cancer is prevalent. While several clinical factors have been identified, the role of genetic predisposition in BCRL development remains underexplored. This study aimed to identify genetic and clinical factors associated with the development of BCRL, focusing on the Gap Junction Protein Alpha-4 (GJA4) rs705193 mutation as a potential biomarker.
METHODS: This prospective cohort study was conducted on 106 breast cancer patients who consecutively underwent ALND in Dharmais Cancer Hospital from October 2022 until October 2024. BCRL was assessed using indocyanine green (ICG) lymphography during a 12-month follow-up. Clinical data were obtained from medical records. The GJA4 rs705193 mutations were analyzed in DNA samples from peripheral blood using Sanger sequencing. A multivariate Cox regression was used to evaluate the association of GJA4 mutation and clinical factors with BCRL.
RESULTS: BCRL developed in 56 (52.8%) patients during follow-up. Subjects with BCRL exhibited a significantly higher body mass index (BMI) than those without BCRL (27.3 vs. 25.0 kg/m2, p = 0.023). GJA4 mutations were identified in 40 (37.7%) patients, comprising 25 (44.6%) patients with BCRL and 15 (30.0%) patients without BCRL. The multivariate Cox regression analysis demonstrated that GJA4 mutation (HR = 1.73, 95% CI: 1.01-2.99, p = 0.047) and BMI (HR = 1.75; 95% CI: 1.02-3.02; p = 0.043) were significantly associated with an increased risk of BCRL.
CONCLUSIONS: The GJA4 rs705193 mutations and elevated BMI independently increase the risk of BCRL in patients undergoing ALND. These findings enable the development of targeted preventive strategies for individuals at high risk.
METHODS: This prospective cohort study was conducted on 106 breast cancer patients who consecutively underwent ALND in Dharmais Cancer Hospital from October 2022 until October 2024. BCRL was assessed using indocyanine green (ICG) lymphography during a 12-month follow-up. Clinical data were obtained from medical records. The GJA4 rs705193 mutations were analyzed in DNA samples from peripheral blood using Sanger sequencing. A multivariate Cox regression was used to evaluate the association of GJA4 mutation and clinical factors with BCRL.
RESULTS: BCRL developed in 56 (52.8%) patients during follow-up. Subjects with BCRL exhibited a significantly higher body mass index (BMI) than those without BCRL (27.3 vs. 25.0 kg/m2, p = 0.023). GJA4 mutations were identified in 40 (37.7%) patients, comprising 25 (44.6%) patients with BCRL and 15 (30.0%) patients without BCRL. The multivariate Cox regression analysis demonstrated that GJA4 mutation (HR = 1.73, 95% CI: 1.01-2.99, p = 0.047) and BMI (HR = 1.75; 95% CI: 1.02-3.02; p = 0.043) were significantly associated with an increased risk of BCRL.
CONCLUSIONS: The GJA4 rs705193 mutations and elevated BMI independently increase the risk of BCRL in patients undergoing ALND. These findings enable the development of targeted preventive strategies for individuals at high risk.