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. 2024 May;67(5):375-383.e3.
doi: 10.1016/j.jpainsymman.2024.01.033. Epub 2024 Feb 1.

Identification Of A Higher Risk Lymphedema Phenotype And Associations With Cytokine Gene Polymorphisms

Christine Miaskowski  1 , Yvette P Conley  2 , Bruce A Cooper  3 , Steven M Paul  3 , Betty J Smoot  4 , Marilyn J Hammer  5 , Mei Fu  6 , Jon D Levine  4
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Free article

Identification Of A Higher Risk Lymphedema Phenotype And Associations With Cytokine Gene Polymorphisms

Christine Miaskowski et al. J Pain Symptom Manage. 2024 May.
Free article

Abstract

Context: Breast cancer-related lymphedema (BCRL) is chronic condition that occurs in 5% to 75% of women following treatment for breast cancer. However, little is known about the risk factors and mechanisms associated with a worse BCRL profile.

Objectives: Identify distinct BCRL profiles in women with the condition (i.e., lower vs. higher risk phenotype) and evaluate for associations with pro- and anti-inflammatory genes.

Methods: Latent class profile analysis (LCPA) was used to identify the BCRL profiles using phenotypic characteristics evaluated prior to surgery. Candidate gene analyses were done to identify cytokine genes associated with the two BCRL profiles.

Results: Of the 155 patients evaluated, 35.5% (n = 55) were in the Lower and 64.5% (n = 100) were in the Higher Risk classes. Risk factors for membership in the Higher class included: lower functional status, having sentinel lymph node biopsy, axillary lymph node dissection, mastectomy, higher number of positive lymph nodes, and receipt of chemotherapy. Polymorphisms for interleukin (IL)1-beta and IL6 were associated with membership in the Higher Risk class.

Conclusion: The readily available and clinically relevant phenotypic characteristics associated with a worse BCRL profile can be used by clinicians to identify higher risk patients. If confirmed, these characteristics can be tested in predictive risk models. In addition, the candidate gene findings may guide the development of mechanistically-based interventions to decrease the risk of BCRL.

Keywords: Breast cancer; Candidate genes; Cytokines; Inflammation; Lymphedema; Risk profiling.

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Conflict of interest statement

Disclosures The authors have no conflicts of interest to declare.

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