Prevalência de linfedema após tratamento de câncer de mama em pacientes com sobrepeso

O câncer de mama e a neoplasia de maior ocorrencia no mundo, e o linfedema e uma das complicacoes mais frequentes do tratamento. O aumento do indice de massa corporal e um dos fatores de risco para linfedema apos o tratamento do câncer de mama. O objetivo deste estudo foi verificar a incidencia de linfedema em mulheres mastectomizadas com sobrepeso e obesidade. Os resultados mostraram que o risco de linfedema em mulheres com sobrepeso e obesidade foi quatro vezes maior (Odds Ratio, OR=3,887). Quanto maior o indice de massa corporal, maior a probabilidade de linfedema, com aumento do risco relativo de 40% para obesidade II.

RESUMEN | El cáncer de mama es la neoplasia que más ocurre en el mundo, y el linfedema es una de las complicaciones más frecuentes de su tratamiento.El aumento del índice de masa corporal es uno de los factores de riesgo para el linfedema tras el tratamiento de cáncer de mama.El propósito de este estudio fue verificar la incidencia de linfedema en mujeres sometidas a mastectomía y que están con sobrepeso y obesidad.

INTRODUCTION
Breast cancer is the neoplasia of highest incidence among women in developed or developing countries, achieving high rates of morbidity and mortality [1][2][3][4] .Estimates from the American Cancer Society (ACS) for 2016 were approximately 246,660 new cases of breast cancer in women, with 40,000 cases of death for this year 5 .According to the National Cancer Institute of Brazil (INCA), in 2016, 57,960 new cases of breast cancer were estimated in the country 2 .
The emergence of lymphedema is multifactorial and is associated with the dissection of the axillary lymph nodes, caused by radiotherapy, obesity, surgery, recurrence of cancer in the axillary lymph nodes, infection and lymphangitis 13,[19][20][21] .The lymphedema degree is associated with the degree of obesity, because the additional deposition of subcutaneous fat contributes to increase the arm volume and the separation of the deep lymphatic channels 22 .Weight gain after diagnosis of breast cancer is related to radiotherapy, chemotherapy and endocrine therapy 23 .Obesity is a risk factor of infection and delay of the cicatrization process, tumorous reincidence and comorbidities, among other post-operative complications such as seroma, hematoma and axillary web syndrome 24 .In addition, body mass index (BMI) increase, mainly in severe obese (BMI≥40 Kg/m 2 ), causes serious health problems, such as increase in the risk factor for cardiovascular, metabolic, neoplastic and orthopedic diseases [25][26][27] .
Therefore, lymphedema is one of the main complications from the breast cancer treatment, and is associated with adverse psychosocial and physical consequences, interfering on the patient's quality of life 19 .The objective of this study was to verify the lymphedema incidence in mastectomized women with overweight and obesity.

METHODOLOGY
A descriptive, observational, transversal study, in which In total, participated 100 women who had undergone mastectomy and were under physical therapy treatment.The study was conducted from July 2013 to August 2014is at the physical therapy ambulatory of the Cancer Hospital of Pernambuco.

Data collection
The data were collected at the physical therapy ambulatory of the Cancer Hospital of Pernambuco.On their appointment days, the volunteers were invited to participate in the research.The objectives and benefits of our study were made explicit.In case of agreement, they were asked to sign the informed consent form, in accordance with resolution 466/12 from the National Health Council.After the explanation of the procedure to be performed and the signed form, the volunteers were submitted to physiotherapeutic evaluation of the upper limb perimetry.
The anthropometric assessment consisted of calculating the body mass index (BMI).BMI values between 25 and 30 were considered overweight, and BMI>30 was considered obesity 27 .An evaluation form was developed for the selection of patients.All participants had BMI classified as overweight or obesity.Among them, 53% were married, 30% single, 9% divorced and 8% widow.The average age was 52.5 years (SD=7.9).
The lymphedema assessment was performed by perimetry of morbidity rates of the upper limbs.The measurements of the circumference (in centimeters) were taken in eight points.The point of reference was the crook of the arm, to mark the measurements.The latter were taken every 7 cm, in three points below the crook of the arm, with the limb supported, relaxed and in the position of supination and every 7 cm, in three points above the crook of the arm, in addition to the circumference of the wrist and the hand.The measuring tape was placed over the marks mentioned 28 .Lymphedema was diagnosed when the circumference of one or more measurements in the affected side was 2.0 cm bigger than the circumference of the same point in the contralateral limb, according to the protocol established by the HCP of Pernambuco.

Instrumentation
Venosan brand tape was used for the perimetry evaluation.To measure body mass and height, a digital scale (Welmy) was used, reference W200⁄ 5 (capacity of 200 kg) and Welmy stadiometer (200cm) (maximum height of 200cm), placed on a flat surface with good lighting.On the scale, the women were positioned erect and with heels together for the calibration of height and weight.Body mass index (BMI) was calculated by dividing the subject's mass by the square of their height.The mass was recorded in kilograms and the height in meters.

Statistical Analysis
For the statistical analysis, we carried out a simple logistic regression, with the purpose of evaluating the prevalence of lymphedema as a dependent variable, in relation to the predictive factors "overweight" and "obesity" as independent variables.Separately, the predictive factors "overweight" and "obesity level I, II and III" were tested, with the aim to know the individual influence of each factor regarding lymphedema, through the Chi-square test.
To indicate the chance of a person -who is overweight or obese -having lymphedema, the prevalence ratio, the Odds Ratio (OR), the relative risk increase (RRI) and the number needed to cause the condition (NNC) were calculated.We used Microsoft Excel, SPSS18 and EpiInfo.

RESULTS
The population under study was classified according to the parameters stipulated in the body mass index  According to the logistic regression analysis, the chance of lymphedema emergence in women with predictive factors (overweight and obesity) was approximately 4 times (OR=3.887;p<0.05), considering women that were submitted to the same surgical treatment, but did not present overweight or obesity.The probability for the development of lymphedema was 37.4% for women with a history of overweight and obesity, and 13.3% for those who did not have these risk factors.
The Chi-square test found no significant difference (p=0.308) in the prevalence of lymphedema in overweight individuals, and 11 of them presented lymphedema (11/42).However, the overweight patient is twice more likely to develop lymphedema (OR=2.31),with 12.9% of relative risk increase.
Among the 26 cases of obesity degree I, 12 showed lymphedema (12/26) with a probability six times higher to develop the condition, compared with individuals without the predictive factor (OR=5.57), as shown in Table 1.For every four obese patients, one individual will present lymphedema (NNC=4), with RRI of 32.8% (Table 1).Concerning women that presented obesity II (15), this variable had the highest prevalence ratio (PR=4), as shown in Table 2.There was statistical significance (p=0.020) and OR=7.42, that is, a chance seven times higher for the emergence of lymphedema compared with a patient who is not obese (Table 2).Two cases were observed for obesity III, of which one presented lymphedema, with prevalence ratio of 3.75.The Chi-square did not reach statistical significance.The OR indicated six times more chances of developing lymphedema.

DISCUSSION
A previous study 19 reported that out of the 455 women evaluated, 124 presented lymphedema.Among these, 114 had BMI>25 Kg/m 2 , that is, 91.9% of the overweight or obese women presented lymphedema 19 .People who have a higher BMI need more blood in circulation and higher efficiency of the lymphatic system to keep its flux.Possibly there is an imbalance of the transportation and absorption capacity of the lymph, which increases the risk of lymphedema 29,30 .
The overweight patient is twice more likely to develop lymphedema (OR=2.31).Another study also found that the increase in the arm volume was related to BMI.It was observed that women with higher BMI tended to have a change in the upper limbs volume 13 .However, there was no stratification of overweight and obesity cases.Although the relative risk increase (RRI) has been low in this study, there is a risk to develop the condition (lymphedema): for eight patients with overweight/obesity, one will present lymphedema (NNC=8).
For the cases that presented obesity level I, the risk of developing lymphedema was about six times higher.In other studies, 79% of patients (359 women) presented BMI≥25 and 32% (145 women) had lymphedema, with OR=3.94 19 .Another study reported that 92% of the patients with lymphedema had obesity, however the authors did not specify the obesity degree 31 .Women with BMI≥30 were 3.6 times more likely to develop lymphedema in six months 32 .
The reduction of body weight interferes on the arm volume reduction.The study of Shaw et al. 27 showed a reduction from 24%±12% to 15%±10%.According to Kwan et al. 16 , obese women present OR= 2.34; however, in their study the relationship with the obesity degree was not investigated.Proportionally, in our study, the increased relative risk was 40%, the NNC was only 3 individuals with overweight/obesity for the emergence of a new case of lymphedema.
For the cases of obesity level III, the reduced size of the sample impaired the estimation.Ahmed et al. 6 observed that most women evaluated had BMI>30 Kg/ m 2 and lymphedema.They associated this fact not only to obesity, but found that, at the time of the diagnosis, these women had larger tumors and dissection need of a bigger amount of lymph nodes.However, Demark-Wahnefried et al. 10 found that BMI≥30 was not associated with increased risk of lymphedema in the assessment 30 months after surgery.

CONCLUSION
The analysis of significance indexes, probability and epidemiological indexes of the sample and the predictive factors (overweight and obesity) showed strong interaction between overweight and obesity and the presence of lymphedema.

Graph 1 .
Distribution of patients according to the classification of body mass index (BMI)

Table 1 .
Comparison of lymphedema occurrences among predictive factors -Chi-square tests; relative risk increase (RRI) and the number needed to cause the condition (lymphedema) (NNH)

Table 2 .
Values for the occurrence of lymphedema in relation to predictive factors and the prevalence ratio