PURPOSE To independently evaluate the impact of axillary surgery type and regional lymph node radiation (RLNR) on breast cancer–related lymphedema (BCRL) rates in patients with breast cancer. PATIENTS AND METHODS From 2005 to 2018, 1,815 patients with invasive breast cancer were enrolled in a lymphedema screening trial. Patients were divided into the following 4 groups according to axillary surgery approach: sentinel lymph node biopsy (SLNB) alone, SLNB+RLNR, axillary lymph node dissection (ALND) alone, and ALND+RLNR. A perometer was used to objectively assess limb volume. All patients received baseline preoperative and follow-up measurements after treatment. Lymphedema was defined as a ≥ 10% relative increase in arm volume arising > 3 months postoperatively. The primary end point was the BCRL rate across the groups. Secondary end points were 5-year locoregional control and disease-free-survival. RESULTS The cohort included 1,340 patients with SLNB alone, 121 with SLNB+RLNR, 91 with ALND alone, and 263 with ALND+RLNR. The overall median follow-up time after diagnosis was 52.7 months for the entire cohort. The 5-year cumulative incidence rates of BCRL were 30.1%, 24.9%, 10.7%, and 8.0% for ALND+RLNR, ALND alone, SLNB+RLNR, and SLNB alone, respectively. Multivariable Cox models adjusted for age, body mass index, surgery, and reconstruction type showed that the ALND-alone group had a significantly higher BCRL risk (hazard ratio [HR], 2.66; P = .02) compared with the SLNB+RLNR group. There was no significant difference in BCRL risk between the ALND+RLNR and ALND-alone groups (HR, 1.20; P = .49) and between the SLNB-alone and SLNB+RLNR groups (HR, 1.33; P = .44). The 5-year locoregional control rates were similar for the ALND+RLNR, ALND-alone, SLNB+RLNR, and SLNB-alone groups (2.8%, 3.8%, 0%, and 2.3%, respectively). CONCLUSION Although RLNR adds to the risk of lymphedema, the main risk factor is the type of axillary surgery used.
Objective The objectives of this study were to determine whether patients reporting symptoms are more likely to develop lymphedema and to describe the temporal relationship between symptom onset and lymphedema. Methods This was a prospective longitudinal cohort study of 647 women treated for breast cancer and screened for lymphedema using arm volume measurements and subjective questionnaires (n = 647; 2284 questionnaires [median 3.5 per patient, range = 1–24]). Primary study outcome was lymphedema (relative volume change ≥10%). The Kaplan–Meier method was used to estimate cumulative lymphedema incidence. Cox proportional hazards models were used to assess the relationship between symptoms, other risk factors, and lymphedema. Results Sixty-four patients (9.9%) developed lymphedema. On multivariable analysis, patients reporting increased arm size (hazard ratio = 3.09, 95% CI = 1.62–5.89) were more likely to progress to lymphedema than those who did not report this symptom. Of those who developed lymphedema, 37 (58%) reported an increased arm size a median of 6.1 months before lymphedema onset (range = −68.6 to 50.2 months). Conclusions Patients at risk of lymphedema who report increased arm size might do so prior to lymphedema onset and are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without objective or observable edema, these patients should be followed vigilantly and considered for early intervention. Symptoms should be incorporated into screening and diagnostic criteria for lymphedema. Impact This study shows that patients at risk for breast cancer-related lymphedema who report increased arm size should be considered at high risk for progression to lymphedema—even without edema on measurement or clinical examination—and should be followed vigilantly, with consideration of early intervention.
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