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The intervention group will receive a total of 24 sessions of Therapeutic Resistance Exercise, distributed in 2 weekly sessions of 50 minutes during 3 months.

The control group will receive an educational booklet containing generalized mobility exercises such as frontal and lateral shoulder raises and rotations (hands to head, hands behind back). This is usually the usual treatment, since in most centers, patients are only referred for treatment of LACM when it is already established.

Strength exercises will be aimed at large muscle groups, such as the shoulder, chest, back and also muscle groups of the lower extremities. In the initial 2 weeks, intervention will start with low intensities of around 55-65% of 1RM, which allows to perform around 15-20 repetitions. The first week there will be performed 2 series, while in the second week it will be 3 series.

Moderate intensity in the 2nd week, corresponding to 65-75% of 1RM and allowing for around 8-12 repetitions. 3 series will be maintained throughout this period of time.In addition to the progressive change in intensity, throughout the intervention the load will be increased by 5-10% when the patient performs the exercise too easily or when they can perform more repetitions than estimated. Rest between sets will be 2-3 minutes.

Resistance Therapeutic Exercise

Cristina Roldán-Jiménez, PhD

The objective of this study is 1) to study the acute and chronic effect of resistance therapeutic physical exercise (RTPE) in the prevention of breast cancer-related lymphedema (BCRL) in breast cancer survivors at risk using variables related to the lymphatic response; 2) Study the possible relationship between changes in body composition at a local and regional level and volume changes produced by RTPE in patients at risk of suffering from BCRL.

Nowadays, research studies that confirm the safety and preventive effect of resistance or strength exercise in breast cancer-related lymphedema (BCRL) have been limited to the study of changes in variables related to the lymphatic response, such as bioimpedance spectroscopy , X-ray absorptiometry, perometry or water displacement after completion of a resistance exercise program (chronic effect).

To better understand the preventive effect of resistance exercise on the BCRL, in addition to studying the variables that are globally accepted and studied at a regional level such as the volume due to water displacement, variables that measure changes at a regional level related to body composition, such as such as echogenicity and ultrasound thickness, local tissue water and mechanical properties of tissues. Furthermore, this would allow us to detect possible changes in different body regions of the upper quadrant (upper extremity, but also breast or back), and not only taking global changes into account. On the other hand, the lymphatic response should be studied in the short term (acute effect), in the long term after an exercise program (chronic effect), as well as in the short term after the training period with possible adaptations to the lymphatic system that could explain the preventive effect.

Therefore, although there is a strong degree of scientific evidence to include therapeutic strength physical exercise as a preventive tool for LACM, the possible physiological mechanisms involved are unknown. The aim of the present project is to tudy the acute and chronic effect of resistance therapeutic physical exercise (RTPE) in the prevention of breast cancer-related lymphedema (BCRL) in breast cancer survivors at risk using regional but also local variables related to the lymphatic response, as well as to study between changes in these variables, body composition at a local and regional level and volume changes produced by RTPE in breast cancer survivors at risk of suffering from BCRL

Blinding of the researchers in charge of the evaluations and data analysis will be implemented, so that they are unaware of the assignment of each patient to the groups. It is not possible to blind participants and the physiotherapist (care provider) due to the very nature of the intervention

Lymphatic Response to Resistance Exercise in Breast Cancer Survivors

Prevention-Related Lymphatic Response to Resistance Exercise in Breast Cancer Survivors at Risk of Breast Cancer-Related Lymphedema

The volume of both extremities will be measured to obtain the difference between both, which will be used as a relative criterion to determine the preventive effect of the intervention, determining the appearance of LACM as those cases in which the patient reaches a difference after one year of follow-up. volume equal to or greater than 10% between both extremities. It will be measured using water displacement volumetry, considered the gold standard for measuring the volume of the affected limb.

The EFC of the affected and contralateral side (liters, l) will be obtained. Which will allow establishing the ECF radius between the extremities. This ratios will be allowed to estimate L-Dex. The L-Dex ratio ranges between -10 and +10, taking into account the ratio between the dominant and non-dominant arms, which is equivalent to impedance ratios of 0.935 to 1.139 for the dominant arms at risk and from 0.862 to 1.066 for non-dominant arms at risk, respectively. It will be obtained through bioimpedance spectroscopy

Local tissue water will be measured by bilateral tissue dielectric constant (TDC). values on the forearm and biceps using the MoistureMeterD Compact. PWC%= 100%x(TDC-1)/77.5. It will be measured on the anterior and posterior aspects of the arm and forearm, on the breast, on the lateral aspect of the shoulder and in the dorsal area.

It will be obtained through the analysis of ultrasound images. The thickness will be measured in millimeters (mm). It will be measured on the anterior and posterior aspects of the arm and forearm, on the breast, on the lateral aspect of the shoulder and in the dorsal area.

It will be obtained through the analysis of ultrasound images. Echogenicity or echointensity refers to the average value obtained from a histogram generated from an 8-bit gray scale. This analysis does not have units of measurement, but provides a numerical value between 0 and 255. It will be measured on the anterior and posterior aspects of the arm and forearm, on the breast, on the lateral aspect of the shoulder and in the dorsal area.

It will be measured with a MyotonPRO portable device (Myoton AS, Estonia), whose probe will be placed on the surface of the skin and produce a mechanical stimulus that will provide five parameters: Tone (Hz), Dynamic stiffness (N/m), Elasticity (unit relative), Relaxation time (ms) and Fluency (relative unit). It will be measured on the anterior and posterior aspects of the arm and forearm, on the breast, on the lateral aspect of the shoulder and in the dorsal area.

it will be measured using the European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire (EORTC QLQ-BR23). This is an EORTC QLQ-C30 breast cancer module that contains 23 items that assess disease symptoms, treatment side effects, body image, sexual functioning, and future outlook. All items are rated on a 4-point scale (1, not at all to very much). Higher scores represent better functioning and higher symptom scores show greater problems. Cronbach's α ranged from 0.46 to 0.94, showing high reliability.

Abduction and flexion of the shoulder joint complex will be measured. It will be measured in a sitting position, ensuring that there is no movement of the trunk, using a digital inclinometer.

It will be measured using the Jamar Hydraulic Hand dynamometer. All participants will sit in a chair without armrests, with their feet on the floor and their back straight, holding the dynamometer with their dominant arm. The elbow was flexed at 90° and the wrist was in a neutral position (0°). Maximum isometric voluntary contractions will be performed for 5 seconds. The force will be expressed in kg. Of the 3 measurements carried out, the peak force will be recorded in units of Newtons (N) or in Kilograms (Kg), obtained from both extremities

It will be measured using the Shoulder Pain and Disability Index (SPADI) questionnaire. SPADI consists of 13 items that are distributed in two different subscales: one related to pain, which contains 5 items, and another related to disability, which contains 8 items. Scoring of items in both subscales is on a scale ranging from 0 (indicating absence of pain or disability) to 10 (representing the worst pain imaginable or such significant difficulty in performing tasks that help is needed). The higher the score on each subscale, the greater the pain intensity and the greater the disability experienced by the individual evaluated.

It will be measured using the Spanish version of the Breast Cancer and Lymphedema Symptom Experience Index (BCLE-SEI) questionnaire.This questionnaire consists of 2 parts: Part 1 is made up of 24 items and evaluates the symptoms of LACM using a Likert scale from 0 (absence of a certain symptom) to 4 (greater severity of a certain symptom); Part 2 is made up of 32 items that evaluate the symptom of discomfort, that is, the negative impact and suffering evoked by the experience of lymphedema. Each part is calculated with the sum of all the responses, and in turn they can be added together to obtain a total score

It will be measured using the Spanish version of Fear-Avoidance component scale (FACS). The FACS contains 20 separate items that are scored from 0 ("completely disagree") to 5 ("completely agree"), with a total possible score of 100. Five severity levels are available for clinical interpretation: subclinical (0-20), mild (21-40), moderate (41-60), severe (61-80), and ex- treme (81-100). This questionnaire has been validated in breast cancer population, showing good psychometric properties.

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