Background: With increasing breast cancer survival, more women are experiencing complications from breast cancer therapy. Arm lymphedema (ALE), one of the most common post-treatment conditions, is associated with both physical and psychological challenges. As there is no definitive cure for ALE, preventive measures are desired; more research is needed to study modifiable factors. Although previous studies investigated ALE, data from long-term prospective cohort studies are sparse. This study aims to assess timing of ALE onset and to identify epidemiological characteristics associated with developing the condition using long-term follow-up data.

Methods: Data were collected from 672 female breast cancer survivors aged 35-64 at diagnosis participating in the HEAL Study, a population-based, multi-center, multi-ethnic prospective cohort study. Women diagnosed with in situ, localized or regional breast cancer were recruited into the HEAL Study through SEER registries in New Mexico (Non-Hispanic Whites and Latinas), Los Angeles County (Blacks), and Western Washington (Non-Hispanic Whites). Participants provided information on sociodemographic factors, anthropometric factors, hormone use, and lifestyle factors at, on average, 6.2 months after diagnosis. Clinical information was abstracted from SEER registry records and hospital medical records. Women reported presence of ALE and date of first occurrence of ALE at two subsequent questionnaires that occurred, on average, 3.3 years (T1) and 10.2 years (T2) after diagnosis. Time to onset of ALE was calculated as the time from diagnosis until self-reported onset date. Cox proportional hazards models were fit and provided estimates of the hazard ratios (HR) for ALE and its 95% confidence interval (CI) using time since diagnosis as the time scale. Women who died or were lost to follow-up before T2 were censored at T1 because their ALE status after T1 was unknown.

Results: During follow-up, 192 women (29%) experienced ALE; 34 (18%) of these women developed ALE more than three years after diagnosis. The median time to onset of ALE was 11 months (range; 0.5-135). Approximately 58% of women who reported ALE at T1 and completed T2 (n=109) had ALE at T2 (persistent ALE). In a multivariable model, receiving total/modified radical mastectomy (vs. partial/less than total mastectomy; HR=1.43, 95% CI=1.06-1.94), receiving chemotherapy (HR=1.58, 95% CI=1.15-2.17), having 10 or more lymph nodes (LN) removed (vs. no LN removed; HR=3.05, 95% CI=1.81-5.11), having body mass index (BMI)≥30 kg/m2 (vs. BMI<25 kg/m2; HR=1.59, 95% CI=1.09-2.32), and having hypertension (HR=1.47, 95% CI=1.04-2.07) all increased ALE risk. Stratifying by race, hypertension was a risk factor only for black women (HR=2.77, 95% CI=1.67-4.58). Contrary to findings from previous studies, we did not find that radiation therapy increased ALE risk (HR=1.18, 95% CI=0.87-1.58).

Conclusions: This study suggests that ALE can occur years after the initial diagnosis and the majority of ALE persists for a long time. In addition to established risk factors, hypertension was a risk factor, particularly in black women. It is important to increase awareness that ALE can develop later in the survival trajectory and to investigate further the role of hypertension in ALE after breast cancer.

Citation Format: Kayo Togawa, Jane Sullivan-Halley, Yani Lu, Ashley Wilder Smith, Catherine Alfano, Ikuyo Imayama, Anne McTiernan, Marian L. Neuhouser, Huiyan Ma, Rachel Ballard-Barbash, Leslie Bernstein. Risk factors for self-reported arm lymphedema among female breast cancer survivors in Health, Eating, Activity, and Lifestyle (HEAL) Study. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A10.