Predictive Factors of Response to Decongestive Therapy in Patients with Breast-Cancer-Related Lymphedema

Predictive Factors of Response to Decongestive Therapy in Patients with Breast-Cancer-Related Lymphedema

Predictive Factors of Response to Decongestive Therapy in Patients with Breast-CancerRelated Lymphedema Forner-Cordero I, MuÇoz-Langa J, FornerCordero...

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Predictive Factors of Response to Decongestive Therapy in Patients with Breast-CancerRelated Lymphedema Forner-Cordero I, MuÇoz-Langa J, FornerCordero A, et al (Hosp La Fe, Valencia, Spain; Univ Hosp Dr Peset, Valencia, Spain; Consejo Superior de Investigaciones Cientficas [CSIC], Madrid, Spain; et al) Ann Surg Oncol 17:744-751, 2010

Background.—Many studies have reported the benefits of decongestive treatment in patients with breastcancer-related lymphedema (BCRL) but few have studied what are the predictive factors of response. Methods.—We performed a prospective, multicenter controlled cohort study of 171 patients with BCRL to identify independent predictive factors of response to decongestive treatment (CDT). Demographic data and clinical and lymphedema characteristics were collected prospectively. The end point was the ‘‘percentage reduction in excess volume (PREV).’’ Volumes were measured prior and at the end of CDT. Factors associated with response (PREV) were tested in univariate and multivariate analyses using linear regression techniques. Results.—Median age was 60.4 years (range 32–84); mean lymphedema chronicity 4 years [95% confidence interval (95% CI): 3.1–5.0]; mean baseline excess volume (EV) was 936 mL (95% CI: 846–1026), and mean percentage EV was 35.3% (95% CI: 32.0–38.7); compliance to bandages was good in 81.3% of patients. PREV

was 71.7% (95% CI: 65.2–78.2). After univariate screening, 11 variables were found to be associated with PREV but only 4 variables were independent predictive factors of response to CDT in the multivariate analysis: Venous insufficiency, percentage of EV (the higher the EV, the lower the reduction with CDT); compliance to bandages (a good compliance improved PREV in 25%), and treatment in autumn (better results than during the rest of the year). Conclusions.—This study shows that compliance to bandages during CDT is one of the most important predictors of response. Moreover, data support the idea that more severe lymphedemas have a worse response to treatment, and it should be recommended in early stages. The association between the season of treatment and response was also very strong, so weather conditions are an additional factor that must be taken into account in further studies. In this non-randomized, prospective, multicenter controlled study, Forner-Cordero and colleagues evaluated the factors that can be associated with a successful outcome of using CDT in a cohort of 171 women who had been treated for breast cancer. The question is important as providers strive for optimal success when treating BCRL. The findings of this study are useful, but we should be careful not to generalize them to the wide spectrum of patients with BCRL because the majority of the study cohort had stage III edema with a significant EV (mean of 35.3% difference between limbs). These characteristics and the length of time patients had experienced symptoms (mean of 4 years) indicate

a cohort that could be defined as having significant and protracted lymphedema. Also, there was no control group in this study. The study design was carefully planned, and Forner-Cordero and colleagues utilized trained therapists to administer CDT and other evaluators to perform measurements and track compliance with bandaging. Although the intervention was referred to as CDT, it also included the use of a pneumatic compression device, which is not a standard component of CDT. Forner-Cordero and colleagues appear to be well versed in lymphedema management, yet it would have been helpful to provide a rationale for adding this device to standard CDT. This study analyzed a thorough list of factors that could influence lymphedema. The authors included venous insufficiency in this list, which is a factor not typically considered in breast cancer populations, but it is interesting and makes reasonable clinical sense. Including more information regarding what criteria were used to evaluate patients for this comorbidity would have strengthened this article, as venous insufficiency was 1 of the 4 factors found to be independently predictive of response to CDT on multivariate analysis. The association of a better treatment outcome with the fall season of the year reported in this article is interesting, and it is a factor that should be included for analysis in other intervention trials that study lymphedema management. The role of bandaging as a predictive factor for a successful outcome has been

Breast Diseases: A Year BookÒ Quarterly Vol 21 No 4 2011


reinforced with these data. However, getting patients to comply with medical regimens is a complex problem, and the suggestions to improve compliance that are outlined in this article are not data driven and may not address the multifaceted aspects of health behavior.

All things considered, this is a worthwhile article. The univariate and multivariate statistical design is good, and the 4 predictive factors that emerged after so many other variables were considered provide useful data to

consider in the management of patients with BCRL.

Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk

associated with a greater reduction in risk (P-trend ¼ 0.01). Risk reduction was observed in women who were not obese (P-interaction ¼ 0.005). Conclusion.—These results are suggestive of an additional benefit of the common use of bisphosphonates, in this instance, the reduction in breast cancer risk.

anatomical sites other than bone, data from an adjuvant trial in premenopausal women with endocrinesensitive breast cancer have suggested that the incidences of not only bone metastases but also contralateral breast cancers, local recurrences, and regional recurrences may be reduced.4 The main problem in assessing these studies is trying to determine the impact of a clinical selection process whereby women with osteopenia and osteoporosis will tend to be on bisphosphonates prior to enrollment in these retrospective studies. Is the reduction in breast cancer incidence due to the bisphosphonates themselves? Or, is it due to the known association between a lower incidence of breast cancer and lower bone mineral density and its obverse, the known higher incidence of breast cancer in women with higher bone mineral density? The statistical exercise of ‘‘adjusting for potentially confounding variables’’ is critical here, and it is difficult to see how this can be done in a manner that is convincing to clinicians without a prospective trial. How do you introduce a corrective factor to account for women who are not on bisphosphonates but have a low bone mineral density when you do not have these data? The history of causative epidemiology is replete with associations that turn out to be surrogates for the actual cause (the

Newcomb PA, Trentham-Dietz A, Hampton JM (Univ of Wisconsin Paul P Carbone Comprehensive Cancer Ctr, Madison) Br J Cancer 102:799-802, 2010

Background.—Bisphosphanates are used primarily for the prevention and treatment of osteoporosis, and are also indicated for osseous complications of malignancy. In addition to their bone resorption properties, the most commonly used nitrogen-containing bisphosphonate compounds also inhibit protein prenylation, and thus may exert anti-tumour properties. Methods.—To evaluate whether the use of these drugs may be associated with cancer, specifically breast cancer, we conducted a populationbased case–control study in Wisconsin from 2003 to 2006. Participants included 2936 incident invasive breast cancer cases and 2975 population controls aged < 70 years. Bisphosphonate use and potential confounders were assessed by interview. Results.—Using multivariable logistic regression, the odds ratio for breast cancer in current bisphosphonate users compared with non-users was 0.67 (95% confidence interval 0.51– 0.89). Increasing duration of use was


Several studies have been published suggesting a link between the use of oral bisphosphonates and the incidence of breast cancer in postmenopausal women.1,2 This article by Newcomb and colleagues is another population-based case-control study supporting the hypothesis that bisphosphonates—through inhibition of the mevalonate pathway (which leads to the prenylation of key signaling proteins required by all cells) as well as through a variety of other mechanisms, such as inhibition of angiogenesis, and prevention of tumor cell adhesion—can influence the growth of neoplastic cells. The authors reported that the use of bisphosphonates was associated with approximately a 30% reduction in breast cancer risk, which is an impressive figure, though not as high as that reported for the preventive use of tamoxifen, which in carefully controlled prospective trials ranges from 40% to 50% for estrogen receptor– positive tumors.3 As further evidence that bisphosphonates have an effect on

Breast Diseases: A Year BookÒ Quarterly Vol 21 No 4 2011

J. O’Toole, PT, MPH, CLT-LANA T. A. Russell, MPH A. G. Taghian, MD, PhD