Factors Affecting Functionality in Breast Cancer Survivors
Condition: Breast Cancer; Breast Cancer Female; Breast Cancer Lymphedema; Breast Carcinoma in Situ; Hand Grasp; Pain, Shoulder
MeSH terms: Breast Neoplasms; Carcinoma in Situ; Breast Carcinoma In Situ; Shoulder Pain; Lymphedema; Breast Cancer Lymphedema
Study type: Observational

Summary: 
      Breast cancer is the most frequent cancer type in women globally. In conjunction with the new
      developments, breast cancer survival has increased therefore the management of long-term
      complications has gained importance. Breast cancer survivors can face the loss of muscle
      strength, increased fatigue and diminished physical function associated with
      treatment-related long term effects and psychological affection and thereby reduced quality
      of life. Upper extremity lymphedema or breast cancer-related lymphedema (BCRL) is one of the
      most prominent long term complications which affects breast cancer survivors in many ways
      after breast cancer surgery. It has been reported that breast cancer survivors with BCRL have
      the lower muscle strength and more activity limitations when compared to the ones free of
      BCRL. In BCRL, affected extremity has been found to 36% more weaker when compared to the
      unaffected side. Fatigue is one of the most prominent symptoms when considering
      cancer-related symptoms in cancer survivors. It has been stated that increased fatigue is
      correlated with increased activity limitation and deterioration in physical function. The
      hand-grip test which is frequently used in the assessment of decreased muscle function has
      been stated as a reliable and repeatable test in breast cancer survivors. In addition, this
      test is frequently applicable to assess mortality, physical and functional capacity, symptoms
      after surgery and to designate an exercise program. There are studies that investigate upper
      extremity function associated with hang-grip strength in breast cancer survivors. Yet, there
      is a lack of the objective result or conclusion of the BCRL effect on upper extremity
      function which is assessed with hang-grip strength when compared without BCRL. Therefore,
      this study is planned to investigate of cumulative effects of factors such as lymphedema
      severity, age, fatigue, body mass index, muscle strength, physical activity level, pain
      level, exercise benefits/barriers scale score on hand-grip strength related upper extremity
      functionality in breast cancer survivors.
    

Detailed description: 
      Investigation of the Factors of Hand-Grip Strength-related Upper Extremity Functionality in
      Breast Cancer Survivors

      Breast cancer is the most frequent cancer type in women globally. In the United States, there
      are almost 3 million breast cancer cases and this number gradually increasing in recent
      years. In conjunction with the new developments, breast cancer survival has increased
      therefore the management of long-term complications has gained importance. Breast cancer
      survivors can face the loss of muscle strength, increased fatigue and diminished physical
      function associated with treatment-related long term effects and psychological affection and
      thereby reduced quality of life. In addition to the reduced quality of life, breast cancer
      survivors experience reduced and altered upper extremity function. The Data not only reported
      by breast cancer survivors but also derived by objective assessment tools state that the high
      prevalence of disrupted upper extremity function. Studies reported that the deterioration of
      shoulder function and reduced strength and flexibility in the range of between 16% to 43%,
      however, these parameters followed a stabile pattern within a year while some parameters
      which are assessed relatively in short periods were found in higher prevalence. In addition
      to these, reduced mobility of head and neck, perceived fatigue, reduced upper extremity
      strength are factors that induce functional limitations in breast cancer survivors.

      Upper extremity lymphedema or breast cancer-related lymphedema (BCRL) is one of the most
      prominent long term complications which affects breast cancer survivors in many ways after
      breast cancer surgery. Lymphedema is characterized by the inability of the function of the
      lymphatic system which can result in the accumulation of protein-rich lymphatic fluid in
      interstitial spaces in addition to skin changes in related body regions and extremities.
      Untreated lymphedema causes chronic inflammation, cellulitis, pain, fatigue, cosmetic
      deformity, restriction in mobility and related problems and therefore ineffective usage of
      the extremity concerning diminished functionality has occurred. It is known that the
      esthetical concern and emotional stress manifested by lymphedema cause deterioration in
      physical function. The heaviness feeling, fibrosis and skin infections caused by lymphedema
      not only can increase psychological stress but also induce musculoskeletal complications in
      the long term. It has been reported that breast cancer survivors with BCRL have the lower
      muscle strength and more activity limitations when compared to the ones free of BCRL. In
      BCRL, affected extremity has been found to 36% more weaker when compared to the unaffected
      side. Through augmented severity and stage of lymphedema, reduced physical functions are
      taken place in the clinical condition. Patients without BCRL can increase their cumulative
      musculoskeletal problems by avoiding physical activity and exercise due to misguidance and
      fear of lymphedema while the ones with BCRL have to fear the increased severity of lymphedema
      by doing so. Lymphedema can bring with problems such as reduced physical activity and weight
      gain thereby constitution of the basis of functional limitations is settled.

      Increased fat mass and body mass index are reported in the range of 50% to %96 in breast
      cancer survivors. Optimal upper extremity function is important for maintaining an
      independent daily life and day routines and to perform works that need physical strength in
      terms of the general quality of life. However, affecting factors and incidence of their
      impact on upper extremity function in the aspect of physical, functional and psychological
      are still have been the research issue. The literature reports that the frequently reduced
      muscle strength due to cancer-related symptoms along with the altered motor control in
      shoulder and neck musculature. Fatigue is one of the most prominent symptoms when considering
      cancer-related symptoms in cancer survivors. It has been stated that increased fatigue is
      correlated with increased activity limitation and deterioration in physical function. The
      hand-grip test which is frequently used in the assessment of decreased muscle function has
      been stated as a reliable and repeatable test in breast cancer survivors. Besides, this test
      is frequently applicable to assess mortality, physical and functional capacity, symptoms
      after surgery and to designate an exercise program.

      Some studies investigate upper extremity function associated with handgrip strength in breast
      cancer survivors. Yet, there is a lack of the objective result or conclusion of the BCRL
      effect on upper extremity function which is assessed with hang-grip strength when compared
      without BCRL. Therefore, this study is planned to investigate of cumulative effects of
      factors such as lymphedema severity, age, fatigue, body mass index, muscle strength, physical
      activity level, pain level, exercise benefits/barriers scale score on hand-grip strength
      related upper extremity functionality in breast cancer survivors.

      The primary purpose of this study:

      This study is planned to investigate of cumulative effects of factors such as lymphedema
      severity, age, fatigue, body mass index, muscle strength, physical activity level, pain
      level, exercise benefits/barriers scale score on hand-grip strength related upper extremity
      functionality in breast cancer survivors.

      Secondary aim:

      Which of the aforementioned parameters has the most prominent effect on hand-grip strength
      related upper extremity functionality in breast cancer survivors

      Primary endpoint:

      Having reached to a targeted number of breast cancer survivors compatible with the incl/excl
      criteria of this study

      Secondary endpoint:

      According to the pilot test result, elimination of parameters that are not significant in the
      statistical model will be excluded and power analysis will be re-performed. If the current
      number of the targeted population has been achieved (by achieving at least 80% power, 95%
      CI), then the study will be finished to save time and resources.

      Center: Single-center study

      Time range: December 2019- October 2020

      Methods:

      109 women aged between 25 and 65 years who had unilateral breast cancer surgery will be
      included in this study (Sample size was determined according to the 0.15 effect size, 80%
      power, and 95% confidence interval). Within the context of this study, an evaluation form
      that assesses demographic information (Both patient and clinical demographics such as Name,
      age, contact information and/or body mass index, time spent after surgery, surgery type, etc)
      will be requested to fill. Within this form, having lymphedema (yes/no), drug use (especially
      tamoxifen, yes/no), pain assessment (via visual analog scale), adjuvant therapies
      (radiotherapy, chemotherapy, yes/no, number of sessions, etc) and shoulder range of motion
      assessment via goniometer will be evaluated and recorded to the assessment form.

      Tissue Dielectric Constant Measurement:

      Sub-tissue fluid proportion will be evaluated via Moisture Meter D (Delfin Technologies,
      Kuopio, Finland) on both upper extremity (right and left) in predefined reference points on
      volar side (6 cm distal and 8 cm proximal points from cubital crease, 10 cm inferior side
      point from axilla and dorsal point of web space in the hand) by using four different probes
      which can assess 0.5 mm, 1.5 mm, 2.5 mm and 5.0 mm depth. Values taken by 2.5 mm depth probe
      will be used to calculate the ratio (affected side TDC value/Unaffected side TDC value) to
      stage lymphedema severity along with the International Society of Lymphology staging system.

      Muscle strength Participants' muscle strength of shoulder flexion, abduction, and elbow
      flexion will be assessed via Handheld digital dynamometer (Lafayette Manual Muscle Tester,
      Model 01165, LaFayette Instruments, NY, USA). Both upper extremities will be assessed three
      times and the average value will be recorded.

      Hand-Grip Strength Handgrip strength will be assessed with LaFayette Professional Hand
      Dynamometer, Model 5030L1, LaFayette Instruments, NY, USA). The standard position which can
      be achieved by 90-degree elbow flexion, shoulder abducted, and hand mid-prone positioned;
      90-degree shoulder abduction and 90-degree shoulder abduction positions will be used to
      assess hang-grip strength. Three measurements will be requested and the maximum value of them
      will be recorded.

      Pain Threshold Measurement The sensitive pain threshold and normal pain threshold will be
      evaluated by a digital algometer (Wagner FDIX, Greenwich, USA) on reference points as
      follows: C5-C6 zygapophyseal joints' lateral points, upper trapezius (proximal, middle and
      distal lateral points, length measured by a tape from C7 Processus spinosus to acromion and
      this length will be divided equally into three parts for proximal, middle and distal lateral
      point), deltoid muscle (deltoid tuberosity), dorsum of the webspace. Measurements will te
      took both for right and left upper extremity. Units will be recorded as kgf.

      Scales and Forms There will be scales and form which are required to fill out by
      participants. The following list of scales will be filled with participants themselves.

      International Physical Activity Questionnaire-Short Form (IPAQ-SF):

      This scale was intended to be filled to assess participants' physical activity levels within
      the last seven days. Then, MET calculations will be done via a basic Excel Spreadsheet which
      is pre-defined MET values formulated inside. Scale data then obtained according to the
      participants' answers and recorded.

      Fatigue Impact Scale:

      This scale has 9 items that can be answered as "Strongly Disagree" through "Strongly Agree"
      by numbered as 1 and 7, respectively. Then total points will be calculated and divided into 9
      to achieve the Fatigue Impact Scale score. The higher points will be indicated more perceived
      fatigue, while lower points indicate less.

      Disabilities of Arm, Shoulder and Hand Scale (DASH):

      DASH has 30 items related to upper extremity function. Participants will be requested to
      grade some expressions related to the function within a 5-point Likert scale as follows: "No
      difficulty: 1, Mild Difficulty:2, Moderate Difficulty: 3, Severe Difficulty: 4 and Unable to
      perform: 5). The symptom score of the DASH will be calculated as dividing filled items total
      score to filled items' number and minus one from this data then multiplying with 25. The
      higher points indicate a deteriorated shoulder and hand function while lower points indicate
      a better upper extremity function.

      Exercise Benefits/ Barriers Scale Exercise Benefits/Barriers Scale has 43 items each can be
      graded within a four-point Likert type scale. Barrier items are reverse coded. 43 items are
      all related to exercise and exercise beliefs in both in the aspect of health and general.
      Strongly disagree, disagree, agree, strongly agree will be scored as 1,2,3,4 or vice versa
      whether the item should de reversely coded, respectively. Total scores ranged between 29 and
      172. The barrier scale score is ranged between 14 and 56. The benefits scale is also ranged
      between 29 and 116. The higher the score of Barriers scale, the greater the perception of
      barriers to exercise.

      Beck Depression Scale

      Beck Depression Scale has 21 items each can be scored within 0 to 3. All items are related to
      the depressive mood of a participant. The higher the score of the Beck Depression Scale, the
      higher the depression level.
    

Intervention name(s): Tissue Dielectric Constant Measurement; Muscle strength measurement; Hand-Grip Strength Measurement; Pain Threshold Measurement; International Physical Activity Questionnaire-Short Form (IPAQ-SF); Fatigue Impact Scale; Disabilities of Arm, Shoulder and Hand Scale (DASH); Exercise Benefits/ Barriers Scale; Beck Depression Scale
Intervention type(s): Other; Other; Other; Other; Other; Other; Other; Other; Other
Intervention description(s): Sub-tissue fluid proportion will be evaluated via Moisture Meter D (Delfin Technologies, Kuopio, Finland) on both upper extremity (right and left) in predefined reference points on volar side (6 cm distal and 8 cm proximal points from cubital crease, 10 cm inferior side point from axilla and dorsal point of web space in the hand) by using four different probes which can assess 0.5 mm, 1.5 mm, 2.5 mm and 5.0 mm depth. Values taken by 2.5 mm depth probe will be used to calculate the ratio (affected side TDC value/Unaffected side TDC value) to stage lymphedema severity along with the International Society of Lymphology staging system. This device mainly aims to assess the dielectric constant of tissues which is related to the amount of tissue water. In the case of pre-lymphedema or lymphedema, one can assess objectively regarding sub-tissue fluid changes via this device. Triplicate measurements will be taken for each reference point.; Participants' muscle strength of shoulder flexion, abduction, and elbow flexion will be assessed via Handheld digital dynamometer (Lafayette Manual Muscle Tester, Model 01165, LaFayette Instruments, NY, USA). Both upper extremities will be assessed three times and the average value will be recorded.; Handgrip strength will be assessed with LaFayette Professional Hand Dynamometer, Model 5030L1, LaFayette Instruments, NY, USA). The standard position which can be achieved by 90-degree elbow flexion, shoulder abducted, and hand mid-prone positioned; 90-degree shoulder abduction and 90-degree shoulder abduction positions will be used to assess hang-grip strength. Three measurements will be requested and the maximum value of them will be recorded. 1 minute resting period will be provided between the positions at which handgrip is assessed.; The sensitive pain threshold and normal pain threshold will be evaluated by a digital algometer (Wagner FDIX, Greenwich, USA) on reference points as follows: C5-C6 zygapophyseal joints' lateral points, upper trapezius (proximal, middle and distal lateral points, length measured by a tape from C7 Processus spinosus to acromion and this length will be divided equally into three parts for proximal, middle and distal lateral point), deltoid muscle (crista deltoidea), dorsum of the webspace.; This scale was intended to be filled to assess participants' physical activity levels within the last seven days. Then, MET calculations will be done via a basic Excel Spreadsheet which is pre-defined MET values formulated inside. Scale data then obtained according to the participants' answers and recorded.; This scale has 9 items that can be answered as "Strongly Disagree" through "Strongly Agree" by numbered as 1 and 7, respectively. Then total points will be calculated and divided into 9 to achieve the Fatigue Impact Scale score. The higher points will be indicated more perceived fatigue, while lower points indicate less.; DASH has 30 items related to upper extremity function. Participants will be requested to grade some expressions related to the function within a 5-point Likert scale as follows: "No difficulty: 1, Mild Difficulty:2, Moderate Difficulty: 3, Severe Difficulty: 4 and Unable to perform: 5). The symptom score of the DASH will be calculated as dividing filled items total score to filled items' number and minus one from this data then multiplying with 25. The higher points indicate a deteriorated shoulder and hand function while lower points indicate a better upper extremity function.; Exercise Benefits/Barriers Scale has 43 items each can be graded within a four-point Likert type scale. Barrier items are reverse coded. 43 items are all related to exercise and exercise beliefs in both in the aspect of health and general. Strongly disagree, disagree, agree, strongly agree will be scored as 1,2,3,4 or vice versa whether the item should de reversely coded, respectively. Total scores ranged between 29 and 172. The barrier scale score is ranged between 14 and 56. The benefits scale is also ranged between 29 and 116. The higher the score of Barriers scale, the greater the perception of barriers to exercise.; Beck Depression Scale has 21 items each can be scored within 0 to 3. All items are related to the depressive mood of a participant. The higher the score of the Beck Depression Scale, the higher the depression level.
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Female Breast cancer survivors aged 25-65 years old who had unilateral breast cancer
        surgery will be enrolled to this study.
      
Keywords: Breast Cancer; Lymphedema; Upper Extremity Function; Hand Grip Strength