Uncontrolled hypertension and the development of lymphedema after breast cancer surgery

Abstract Introduction: Breast cancer is the most common type of cancer among women in the United States with more than 281,550 new cases in 2021. Definitive treatment for early/localized disease includes a combination of surgery, radiation and systemic therapy with high cure rates but significant potential morbidity. Lymphedema (LE) is the chronic swelling of tissue due to damage caused by breast cancer surgery and/or radiation therapy, occurring in approximately 25-60% of patients who undergo axillary dissection with or without radiation. LE is a morbid disease that decreases patient quality of life and has limited treatment options. Thus, identifying risk factors to prevent the development of LE is crucial. To our knowledge, uncontrolled hypertension has not been previously studied as a potential risk factor for the development of arm lymphedema after breast cancer treatment. Methods: In this single institution prospective cohort study, women were enrolled before their surgery for stage 0-III breast cancer. Baseline interviews were conducted and data including ethnic background, weight, medical comorbidities, and medications were collected. Breast cancer clinicopathologic features and treatment were also recorded. Bilateral arm measurements and blood pressure (BP) readings were taken at baseline and intervals of 3 months for up to 5 years after surgery. An increase in volume >5% from baseline was classified as lymphedema. The association between baseline BP and development of lymphedema was tested with univariate Cox regression model. Results: 176 women were enrolled between 1999 and 2004, of which 46% were Caucasian, 42% African American, 12% other. The average age at enrollment was 51 years. 68% were overweight or obese. 11% had Stage 0, 33% Stage I, 42% Stage II, and 14% had Stage III breast cancer. The most common type of surgery was mastectomy (52%) with remaining patients undergoing lumpectomy. Most patients underwent nodal evaluation with 55% receiving axillary node dissection, 40% receiving sentinel node biopsy or axillary node sampling, and 6% undergoing no nodal surgery. 57% of patients underwent chemotherapy and 53% received radiation therapy. At baseline, 65% of the patients reported a history of hypertension, of which approximately 50% were taking antihypertensive medications and 57% had uncontrolled blood pressure (defined as office BP ≥ 140/90). Using the 5% cutoff, 27% of patients developed lymphedema within 5 years after surgery, of which 14% occurred within the first year. Women who were obese, had mastectomy or more than 9 LNs removed were at higher risk of developing LE. Age, ethnicity and cancer stage had no association with the development of LE (Table 1). Women with uncontrolled or controlled hypertension did not have a higher risk for LE compared to those that were normotensive with hazard ratios of 0.82 (95%CI: 0.39, 1.76; p value 0.616) and 0.70 (95%CI: 0.31, 1.59; p value 0.396) respectively. Conclusion: Baseline uncontrolled or controlled hypertension does not increase the risk for the development of LE after surgery and radiation for breast cancer. Further analysis of BP control over time as another risk factor for the development of LE in this dataset is also planned. Identifying BP control as a risk factor for LE would aid in prevention efforts to decrease the development of this morbidity in breast cancer survivors. Table 1. Univariate Cox regression hazard ratios (HR) for development of lymphedema with 5% cutoffVariableEvent/nHR (95% CI)P valueAge at enrollment48/1741.00 (0.98-1.02)0.984RaceCaucasian19/81Ref.African American23/741.53 (0.83-2.82)0.171Other6/201.17 (0.47-2.93)0.741StageI13/58Ref.04/190.74 (0.24-2.29)0.605II25/741.39 (0.71-2.71)0.341III6/251.22 (0.46-3.20)0.693BMINormal9/52Ref.Underweight1/32.95 (0.37-23.43)0.306Overweight15/551.73 (0.76-3.95)0.195Obesity23/652.21 (1.02-4.78)0.044Number of Nodes Removed<917/87Ref.≥931/891.92 (1.06-3.47)0.031ChemotherapyNo20/76Ref.Yes28/1000.95 (0.54-1.69)0.873Radiation therapyNo24/81Ref.Yes23/940.72 (0.41-1.28)0.264Breast surgeryLumpectomy18/84Ref.Mastectomy30/911.84 (1.02-3.31)0.042Nodal surgerySNB or ALN sampling15/70Ref.No axillary surgery2/100.81 (0.19-3.57)0.786ALND31/961.55 (0.83-2.86)0.167 Citation Format: Elizabeth Weisberg, Hadeel Assad, Lydia Choi-Kim, Tammy DeMeere, Hyejeong Jang, Wei Chen, Mary Ann Kosir. Uncontrolled hypertension and the development of lymphedema after breast cancer surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-07.