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Purpose/Objective Lymphedema following breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiotherapy-related risk factors for lymphedema. Methods and Materials From 2005–2012, we prospectively performed arm volume measurements on 1,476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099/1501 (73%) received radiotherapy. Arm measurements were performed pre- and post-operatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months post-operative. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. Results At a median follow-up of 25.4 months (range 3.4–82.6), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiotherapy type was: 3.0% (no radiotherapy), 3.1% (breast or chest wall alone), 21.9% (supraclavicular (SC)), and 21.1% (SC and posterior axillary boost (PAB)). On multivariate analysis, the hazard ratio for RLNR (SC±PAB) was 1.7 (p = 0.025) compared to breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC+PAB (p=0.96). Other independent risk factors included early post-operative swelling (p <0.0001), higher BMI (p<0.0001), greater number of lymph nodes dissected (p =0.018), and axillary lymph node dissection (p=0.0001). Conclusions In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased risk of lymphedema compared to breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease with the increased risk of lymphedema.

Generalized vitiligo is a common autoimmune disorder in which patchy loss of skin and hair pigmentation results from loss of pigment-forming melanocytes from the involved regions. Vitiligo occurs with a frequency of about 1% in most populations, and is highly associated with other autoimmune disorders, particularly Hashimoto thyroiditis. Most cases of vitiligo are sporadic, although some cases cluster in families, and the disorder is thought to be oligogenic in origin. We have studied a large family cluster in which vitiligo and Hashimoto thyroiditis occur in numerous individuals. A whole-genome scan of 24 family members, including 14 affected with autoimmune disease, showed significant linkage of an oligogenic autoimmune susceptibility locus, termed AIS1, to a 14.4 cM interval in 1p31.3-p32.2. A two-locus analysis of Hashimoto thyroiditis in family members segregating an AIS1 susceptibility allele showed suggestive linkage to markers in chromosome 6p22.3-q14.1, in a region spanning both the major histocompatibility complex and AITD1, a susceptibility locus for autoimmune thyroid disease. Our results indicate that the 1p AIS1 locus is associated with susceptibility to autoimmunity, particularly vitiligo, in this family, and that a chromosome 6 locus, most likely AITD1, may mediate the occurrence of Hashimoto's thyroiditis in AIS1-susceptible family members.

Purpose The goal of this study was to investigate the association between blood draws, injections, blood pressure readings, trauma, cellulitis in the at-risk arm, and air travel and increases in arm volume in a cohort of patients treated for breast cancer and screened for lymphedema. Patients and Methods Between 2005 and 2014, patients undergoing treatment of breast cancer at our institution were screened prospectively for lymphedema. Bilateral arm volume measurements were performed preoperatively and postoperatively using a Perometer. At each measurement, patients reported the number of blood draws, injections, blood pressure measurements, trauma to the at-risk arm(s), and number of flights taken since their last measurement. Arm volume was quantified using the relative volume change and weight-adjusted change formulas. Linear random effects models were used to assess the association between relative arm volume (as a continuous variable) and nontreatment risk factors, as well as clinical characteristics. Results In 3,041 measurements, there was no significant association between relative volume change or weight-adjusted change increase and undergoing one or more blood draws (P = .62), injections (P = .77), number of flights (one or two [P = .77] and three or more [P = .91] v none), or duration of flights (1 to 12 hours [P = .43] and 12 hours or more [P = .54] v none). By multivariate analysis, factors significantly associated with increases in arm volume included body mass index ≥ 25 (P = .0236), axillary lymph node dissection (P < .001), regional lymph node irradiation (P = .0364), and cellulitis (P < .001). Conclusion This study suggests that although cellulitis increases risk of lymphedema, ipsilateral blood draws, injections, blood pressure readings, and air travel may not be associated with arm volume increases. The results may help to educate clinicians and patients on posttreatment risk, prevention, and management of lymphedema.

Taxane-based chemotherapy for the treatment of breast cancer is associated with fluid retention in the extremities; however, its association with development of breast cancer-related lymphedema is unclear. We sought to determine if adjuvant taxane-based chemotherapy increased risk of lymphedema or mild swelling of the upper extremity. 1121 patients with unilateral breast cancer were prospectively screened for lymphedema with perometer measurements. Lymphedema was defined as a relative volume change (RVC) of ≥10 % from preoperative baseline. Mild swelling was defined as RVC 5- <10 %. Clinicopathologic characteristics were obtained via medical record review. Kaplan–Meier and Cox proportional hazard analyses were performed to determine lymphedema rates and risk factors. 29 % (324/1121) of patients were treated with adjuvant taxane-based chemotherapy. The 2-year cumulative incidence of lymphedema in the overall cohort was 5.27 %. By multivariate analysis, axillary lymph node dissection (ALND) (p < 0.0001), higher body mass index (p = 0.0007), and older age at surgery (p = 0.04) were significantly associated with increased risk of lymphedema; however, taxane chemotherapy was not significant when compared to no chemotherapy and non-taxane chemotherapy (HR 1.14, p = 0.62; HR 1.56, p = 0.40, respectively). Chemotherapy with docetaxel was significantly associated with mild swelling on multivariate analysis in comparison to both no chemotherapy and non-taxane chemotherapy groups (HR 1.63, p = 0.0098; HR 2.15, p = 0.02, respectively). Patients who receive taxane-based chemotherapy are not at an increased risk of lymphedema compared to patients receiving no chemotherapy or non-taxane adjuvant chemotherapy. Those treated with docetaxel may experience mild swelling, but this does not translate into subsequent lymphedema.

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Purpose Evaluate arm volume measurements and clinico-pathologic characteristics of breast cancer patients to define a threshold for intervention in breast cancer-related lymphedema. Methods We prospectively performed arm volume measurements on breast cancer patients using a Perometer. Arm measurements were performed pre- and post-operatively, and change in arm volume was quantified using a relative volume change (RVC) equation. Patient and treatment risk factors were evaluated. Cox proportional hazards models with time-dependent covariates for RVC were used to evaluate whether RVC elevations of ≥3%-<5% or ≥5%-<10% occurring ≤3 months or >3 months after surgery were associated with progression to ≥10% RVC. Results 1173 patients met eligibility criteria with a median of 27 months post-operative follow-up.The cumulative incidence of ≥10% RVC at 24 months was 5.26% (95% CI: 4.01% – 6.88%). By multivariable analysis, a measurement of ≥5-<10% RVC occurring >3 months after surgery was significantly associated with an increased risk of progression to ≥10% RVC (HR: 2.97, p<0.0001), but a measurement of ≥3-<5% RVC during the same time period was not statistically significantly associated (HR: 1.55, p=0.10). Other significant risk factors included a measurement ≤3 months after surgery with RVC of ≥3–<5% (p=0.007), ≥5–<10% (p<0.0001), or ≥10% (p=0.023), axillary lymph node dissection (ALND) (p<0.0001), and higher BMI at diagnosis (p=0.0028). Type of breast surgery, age, number of positive or number of lymph nodes removed, nodal radiation, chemotherapy, and hormonal therapy were not significant (p>0.05). Conclusion Breast cancer patients who experience a relative arm volume increase of ≥3%-<5% occurring >3 months after surgery do not have a statistically significant increase in risk of progression to ≥10%, a common lymphedema criterion . Our data supports utilization of a ≥5-<10% threshold for close monitoring or intervention, warranting further assessment. Additional risk factors for progression to ≥10% include ALND, higher BMI, and post-operative arm volume elevation.

Background Identifying risk factors for lymphedema in patients treated for breast cancer has become increasingly important given the current lack of standardization surrounding diagnosis and treatment. Reports on the association of body mass index (BMI) and weight change with lymphedema risk are conflicting. We sought to examine the impact of pre-operative BMI and post-treatment weight change on the incidence of lymphedema. Methods From 2005-2011, 787 newly-diagnosed breast cancer patients underwent prospective arm volume measurements with a Perometer pre- and post-operatively. BMI was calculated from same-day weight and height measurements. Lymphedema was defined as a relative volume change (RVC) of ≥10%. Univariate and multivariate Cox proportional hazards models were used to evaluate the association between lymphedema risk and pre-operative BMI, weight change, and other demographic and treatment factors. Results By multivariate analysis, a pre-operative BMI ≥30 was significantly associated with an increased risk of lymphedema compared to a pre-operative BMI <25 and 25-<30 (p = 0.001 and p = 0.012, respectively). Patients with a pre-operative BMI 25-<30 were not at an increased risk of lymphedema compared to patients with a pre-operative BMI<25 (p= 0.409). Furthermore, large post-operative fluctuations in weight, regardless of whether they reflected weight gain or loss (i.e. 10 pounds gained/lost per month), resulted in a significantly increased risk of lymphedema (HR: 1.97, p = <0.0001). Conclusions Pre-operative BMI of ≥30 is an independent risk factor for lymphedema, whereas a BMI of 25-<30 is not. Large post-operative weight fluctuations also increase risk of lymphedema. Patients with a pre-operative BMI≥30 and those who experience large weight fluctuations during and after treatment for breast cancer should be considered at higher-risk for lymphedema. Close monitoring or early intervention to ensure optimal treatment of the condition may be appropriate for these patients.