Multimodal Treatments and the Risk of Breast Cancer-related Lymphedema: Insights from a Nationally Representative Cohort in South Korea

Overview

Journal BMC Cancer

Publisher Biomed Central

Date 2025 Jan 23

PMID 39844110

Authors

Sung Hoon Jeong

Seong Min Chun

Miji Kim

Ye Seol Lee

Jisun Kim

Ja-Ho Leigh

Yoon-Hee Choi

Affiliations

Soon will be listed here.

Abstract

Background: As the roles of chemotherapy (Chemo) and radiation therapy (Radio) in the definitive treatment of breast cancer have expanded, a broader understanding of the factors associated with breast cancer-related lymphedema (BCRL) has become increasingly essential. Therefore, we investigated the association between multimodality treatment and the risk of BCRL.

Methods: In this retrospective study conducted using National Health Insurance data and the Korea National Cancer Incidence Database (2006-2017), 114,638 participants who underwent Surgery (Surg) or Chemo within 6 months after breast cancer diagnosis were enrolled, and the effect of multimodality treatment on the risk of BCRL was analyzed using the Cox proportional-hazards model. Multimodality treatment administered through six months of treatment was grouped as only Surg; Surg/Chemo; Surg/ Chemo/Radio; Surg/Radio; only Chemo; and Chemo/Radio.

Results: The risk of BCRL was higher in the Surg/Chemo group (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.43-1.65), Surg/Chemo/Radio group (HR: 1.51, 95% CI: 1.43-1.65), only Chemo group (HR: 1.58, 95% CI: 1.45-1.71), and Chemo/Radio group (HR: 1.13, 95% CI: 1.00-1.29) in comparison with the only Surg group.

Conclusion: BCRL occurrence is an after-effect of complex breast cancer treatments, and the risk may vary depending on the treatment method, including Surg, chemo, and radio. Our findings suggest that multidisciplinary strategies are required to minimize the risk of BCRL development in patients with breast cancer.

References

Kim P, Lee J, Lim O, Park H, Park K . Quantitative Lymphoscintigraphy to Predict the Possibility of Lymphedema Development After Breast Cancer Surgery: Retrospective Clinical Study. Ann Rehabil Med. 2018; 41(6):1065-1075. PMC: 5773427. DOI: 10.5535/arm.2017.41.6.1065. View

Giuliano A, Hunt K, Ballman K, Beitsch P, Whitworth P, Blumencranz P . Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011; 305(6):569-75. PMC: 5389857. DOI: 10.1001/jama.2011.90. View

Shah C, Arthur D, Riutta J, Whitworth P, Vicini F . Breast-cancer related lymphedema: a review of procedure-specific incidence rates, clinical assessment AIDS, treatment paradigms, and risk reduction. Breast J. 2012; 18(4):357-61. DOI: 10.1111/j.1524-4741.2012.01252.x. View

Lee J, Hur H, Lee J, Youn H, Han K, Kim N . Long-term risk of congestive heart failure in younger breast cancer survivors: A nationwide study by the SMARTSHIP group. Cancer. 2019; 126(1):181-188. DOI: 10.1002/cncr.32485. View

Togawa K, Ma H, Sullivan-Halley J, Neuhouser M, Imayama I, Baumgartner K . Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study. Breast Cancer Res. 2014; 16(4):414. PMC: 4189147. DOI: 10.1186/s13058-014-0414-x. View

Pedersen A, Mikkelsen E, Cronin-Fenton D, Kristensen N, Pham T, Pedersen L . Missing data and multiple imputation in clinical epidemiological research. Clin Epidemiol. 2017; 9:157-166. PMC: 5358992. DOI: 10.2147/CLEP.S129785. View

Shen A, Lu Q, Fu X, Wei X, Zhang L, Bian J . Risk factors of unilateral breast cancer-related lymphedema: an updated systematic review and meta-analysis of 84 cohort studies. Support Care Cancer. 2022; 31(1):18. DOI: 10.1007/s00520-022-07508-2. View

McLaughlin S, Wright M, Morris K, Sampson M, Brockway J, Hurley K . Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: patient perceptions and precautionary behaviors. J Clin Oncol. 2008; 26(32):5220-6. PMC: 2652092. DOI: 10.1200/JCO.2008.16.3766. View

Miller C, Specht M, Skolny M, Horick N, Jammallo L, OToole J . Risk of lymphedema after mastectomy: potential benefit of applying ACOSOG Z0011 protocol to mastectomy patients. Breast Cancer Res Treat. 2014; 144(1):71-7. PMC: 4011490. DOI: 10.1007/s10549-014-2856-3. View

10.

Ahn H, Jeong H, Jeong C, Kang S, Jung S, Youn H . Incidence and risk factors of breast cancer-related lymphedema in Korea: a nationwide retrospective cohort study. Int J Surg. 2024; 110(6):3518-3526. PMC: 11175813. DOI: 10.1097/JS9.0000000000001278. View

11.

McLaughlin S, Brunelle C, Taghian A . Breast Cancer-Related Lymphedema: Risk Factors, Screening, Management, and the Impact of Locoregional Treatment. J Clin Oncol. 2020; 38(20):2341-2350. PMC: 7343436. DOI: 10.1200/JCO.19.02896. View

12.

Gnerlich J, Deshpande A, Jeffe D, Sweet A, White N, Margenthaler J . Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease. J Am Coll Surg. 2009; 208(3):341-7. PMC: 3262236. DOI: 10.1016/j.jamcollsurg.2008.12.001. View

13.

Seong S, Kim Y, Khang Y, Park J, Kang H, Lee H . Data Resource Profile: The National Health Information Database of the National Health Insurance Service in South Korea. Int J Epidemiol. 2016; 46(3):799-800. PMC: 5837262. DOI: 10.1093/ije/dyw253. View

13.

Rakita A, Nikolic N, Mildner M, Matiasek J, Elbe-Burger A . Re-epithelialization and immune cell behaviour in an ex vivo human skin model. Sci Rep. 2020; 10(1):1. PMC: 6959339. DOI: 10.1038/s41598-019-56847-4. View

14.

Rokitka D, Heffler J, Zevon M, Kitcho C, Schweitzer J, Rodriguez E . Designing an exercise intervention for adult survivors of childhood cancers. BMC Cancer. 2021; 21(1):1. PMC: 7784286. DOI: 10.1186/s12885-020-07763-8. View

14.

Konishi T, Tanabe M, Michihata N, Matsui H, Nishioka K, Fushimi K . Risk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients. Breast Cancer. 2022; 30(1):36-45. DOI: 10.1007/s12282-022-01395-5. View

15.

Suissa S . Immortal time bias in pharmaco-epidemiology. Am J Epidemiol. 2007; 167(4):492-9. DOI: 10.1093/aje/kwm324. View

16.

Shaitelman S, Chiang Y, Griffin K, DeSnyder S, Smith B, Schaverien M . Radiation therapy targets and the risk of breast cancer-related lymphedema: a systematic review and network meta-analysis. Breast Cancer Res Treat. 2016; 162(2):201-215. DOI: 10.1007/s10549-016-4089-0. View

17.

DiSipio T, Rye S, Newman B, Hayes S . Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013; 14(6):500-15. DOI: 10.1016/S1470-2045(13)70076-7. View

18.

Tsai R, Dennis L, Lynch C, Snetselaar L, Zamba G, Scott-Conner C . The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors. Ann Surg Oncol. 2009; 16(7):1959-72. DOI: 10.1245/s10434-009-0452-2. View