Assessing Fine Motor and Sensory Functions In Patients With Breast Cancer At Risk for Chemotherapy Induced Peripheral Neuropathy (CIPN)

Assessing Fine Motor and Sensory Functions In Patients With Breast Cancer At Risk for Chemotherapy Induced Peripheral Neuropathy (CIPN) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Assessing Fine Motor and Sensory Functions In Patients With Breast Cancer At Risk for Chemotherapy Induced Peripheral Neuropathy (CIPN) Alper Tuğral, Zeynep Arıbaş, Murat Akyol, Yeşim Bakar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1419318/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: This study was aimed to assess potential Chemotherapy-Induced Peripheral Neuropathy (CIPN) related motor and sensorial deficits in patients with breast cancer undergoing chemotherapy. This study was registered to Clinical Trials with the following unique number: NCT04799080. Methods: 27 female patients (Mean age: 51.59±10.55 year) were assessed in three different time points as follows: T1 (before chemotherapy), T2 (interim analysis), and T3 (completion of chemotherapy). Motor function was assessed with handgrip strength (HGS) and peripheral muscle strength (PMS). Semmens Weinstein Monofilament Test was used to assess the potential sensory loss. Minnesota Manual Dexterity Test (MMDT) was used to assess fine motor function. Fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Module Cancer Related Fatigue (EORTC-QLQ-FA12) Results: HGS was not found significant among all three assessment time points (F (2,52) =0.590, p=0.558). PMS was found significant (F (2,52) =4.058, p=0.023). Bonferroni post-hoc test revealed that PMS was significantly decreased between T1 and T2 (170.38±30.79 N vs 154.41±23.79 N, mean difference=15.972, p=0.046, respectively). Cutaneous sensory tactile function (p>0.05) and MMDT (F (2,52) =0.789, p=0.460) did not change significantly from T1 through T3. In T3, fatigue and PMS was found significantly correlated (r=-0.636, p=0.002). Conclusions: CIPN related problems affect a great number of cancer survivors. Establishing knowledge and awareness associated with CIPN as well as its early recognition and detection might improve patient-centered clinical outcomes in oncology setting. Breast cancer chemotherapy Chemotherapy Induced Peripheral Neuropathy Fatigue Tactile sense Peripheral muscle strength Figures Figure 1 Introduction According to the 2018 data, World Health Organization reported that over two million new cancer cases worldwide [ 1 ]. Though the incidence of cancer and rates are increasing, long-term survival after cancer treatment is also increased due to the advancements in cancer treatment as well as early diagnosis. It was reported that the number of cancer survivors is expected to be over 18 million by 2022. Because of increased survivorship of cancer, short and long-term issues which affect cancer survivors in many aspects take attention in order to optimize the quality of life of them [ 2 ]. Chemotherapy (CT) which is a common standard of care of cancer patients proven as effective, however, some CT drugs have highly deleterious neurotoxic effects which affect nerves and related structures [ 3 , 4 ]. Chemotherapy-induced peripheral neuropathy (CIPN) is accepted as a side effect of CT drugs which manifest predominantly sensory disturbances and ultimately result in a decrease in functional capacity and quality of life among cancer survivors. Although incidence and prevalence rates vary, it is reported as at least 40% of patients who undergo CT develops CIPN, while in some CT drugs such as taxanes, this rate might be high as 87% [ 5 , 6 ]. Studies reported that approximately 33% of patients develop CIPN during the CT period which may persist up to two years [ 7 , 8 ]. Hypersensitivity and loss of sensation can manifest as stock and glove-like distribution. Numbness, tingling, discomfort, and pain especially in the distal part of both upper and lower body are the most common symptoms who suffer from CIPN in cancer survivors. A vicious cycle of symptom aggravation might be prominent due to affected both fine and gross motor skills as well as increased risk of falling due to decreased proprioception sense [ 9 – 11 ]. Drugs used in CT are shown as a detrimental factor for not only sensory loss but also muscle loss. Muscle atrophy and dysfunction are attributed to diminished motor innervation while high dose corticosteroid treatment can cause mitochondrial damage of muscles. Thereby, generalized muscle weakness especially in taxanes, and related functional loss might occur [ 12 , 13 ]. Patients undergoing CT reported that there is lacking information about CIPN [ 14 ]. Since there has been no standardized protocol for the prevention of CIPN, detailed monitoring and guidance are needed. Proactive assessment and screening for both sensory and motor functions including fine motor skills require specific equipment and knowledge which can be performed by physical therapists [ 15 ]. As mentioned above, CIPN needs continuously monitoring due to its chronic nature not only during the CT process but also during the survivorship. Thereby, we aimed to prospectively assess CIPN related motor and sensorial deviations in patients undergoing CT in this study. Methods Study Design This study was planned as an observational-cross sectional cohort study in a prospective longitudinal design and registered in clinical trials with the unique identification number as following: NCT04799080. All procedures and measurements in this study were performed according to 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval was granted by Izmir Bakircay University Ethical Board of Clinical Studies with the 208/190/04032021 protocol number before enrollment of patients. Patients Patients who applied to the medical oncology unit for systemic adjuvant or neoadjuvant chemotherapy were screened according to the predetermined inclusion and exclusion criteria. Patients who volunteered to participate in this study were initially informed about the study process and signed consent was taken for each of them. Thereafter, information of demographic and clinical features such as gender, age, diagnosis, stage, drugs, surgical, medical, and social anamnesis were gathered by a simple assessment form. Being a volunteer to participate, having been diagnosed with breast cancer, and being a candidate for CT were set as inclusion criteria. Having sensory loss due to diabetic polyneuropathy, having extensive scar tissue at hands and/or foot which may hamper assessing sensorial function, having disorders or disabilities which includes neural functional deficits such as multiple sclerosis was set as exclusion criteria. Patients recruited from medical oncology unit in Izmir Bakircay University Çiğli State and Teaching Hospital. Eligible patients according to the aforementioned criteria were screened to enroll to this study. 29 Patients fulfilled the inclusion criteria; however, this pilot study was completed with a total of 27 breast cancer patients. One patient moved to another city while the other one did not fulfill the all assessments. Assessment Tools and Protocol The main purpose(s) of this study was to evaluate the effect of CIPN on motor and sensory functions. Repeated measurements were set as in three different time points as following: Time 1 (T1): prior to chemotherapy, Time 2 (T2): interim time point (approx.8 weeks later) and Time 3 (T3): post-chemotherapy time point (12–20 weeks later after initial assessment). The main outcome measures were set as handgrip strength, peripheral muscle strength (PMS) and Minnesota Manual Dexterity Test (MMDT) for motor function. Semmens-Weinstein Monofilament Test (SWMT) was set for sensory evaluation. Secondarily, patients' fatigue was assessed with The European Organization for Research and Treatment of Cancer Quality of Life Module Cancer Related Fatigue (EORTC-QLQ-FA12) questionnaire. Handgrip Strength Since CIPN usually manifest itself distally, we chose to assess motor function by measuring Hand-Grip Strength as mentioned and suggested in the literature [ 15 ]. Handgrip strength was 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 adducted, and hand positioned in mid-prone was used to assess hand-grip strength. The patient was asked to squeeze the dynamometer as much as she can without holding her breath and preserving her erect posture. Three measurements were requested and average of three measurements was recorded for each side. 60 seconds interval was integrated between each measurement. Peripheral Muscle Strength Reports suggest that objective motor function tests can be used in patients at risk for CIPN. In lower extremity, reduced strength was shown as correlated with increased fall risk [ 16 , 17 ]. Thereby, we chose to assess quadriceps femoris (QF) strength which is quite important for both performing task specific functions and safe ambulation in daily life. Patients were asked to sit in an erect position while their hands are crossed in her shoulders. One of the authors (A.T) performed the manual muscle strength test bilaterally for knee extension. 3 seconds was arranged to take muscle strength and peak force was recorded as Newton (N) (Lafayette Manual Muscle Tester, Lafayette, USA). Triplicate measurements were performed for each side and average of three measurements was recorded. During the test, patients were required to preserve their erect posture without holding their breath. 60 seconds interval was integrated between each measurement. Semmens-Weinstein Monofilament Test Cutaneous sensation of patients was assessed with Semmens-Weinstein Monofilament Test (SWMT) in bilaterally palmar and plantar surface of hand, foot, and fingers in predefined reference points (Fig. 1). Patients were informed prior to testing as they must close their eyes during testing and if anything felt, it is requested to say “yes” or “I felt”. The test was started with the smallest 2.83 monofilament (0.07 gram) and three repetitions were done. Monofilaments were applied perpendicular to the site for 1.5-2 seconds and then removed. If one of them was felt by patient, cutaneous sensation was recorded as mechanical detection threshold. In case of CIPN, it is expected to be greater monofilament due to greater force is required [ 18 , 19 ]. Minnesota Manual Dexterity Test Hand function or dexterity, which includes both gross and fine motor movements is crucial for daily functional life. Minnesota Manual Dexterity Test (MMDT) have been used in different hand disabilities or injuries as well as to evaluate rehabilitation results of hand. MMDT was developed in early 90’s by Lafayette Instrument Company (Lafayette Instruments, Lafayette, USA). Briefly, 60 round plastic discs should be placed or removed in a board which is organized in a 4 x 15 pattern [ 20 , 21 ]. One is asked to be positioned standing in front of the board. In the top right corner, which is the start point, one should grasp the disc with his/her right hand, then turn its other side and replace it with his/her left hand. This pattern is changed when his/her reach the left side of the board by grasping the disc with his/her left hand and replace it with the right hand. Although, different subtests are available such as placing or removing the discs by performed with the dominant hand or both hands; we chose to “lifting and turning” test which requires bilateral performance for both hands due to potential CIPN can affect both hands. Fatigue Assessment The EORTC-QLQ-FA12 questionnaire was used to assess fatigue in the pre-CT and post-CT period (T1 and T3). It assesses physical, emotional, and cognitive aspects of cancer related fatigue. The EORTC-QLQ Questionnaire and its sub-modules are the most frequently used cancer-specific health-related questionnaires. It consists of 12 items, and each is scored “1: None” through “4: A lot” according to the 4 point Likert Scoring System. Total score ranges from 0 through 100. The higher scores indicate worse quality of life or vice versa [ 22 ]. Statistical Analysis Since three different time points were planned in this study design, repeated measures analysis of variance within factor (ANOVA) was used. A priori power analysis showed 54 participants are needed to be included according to the moderate level partial eta squared and effect size which are calculated by G*Power 3.1.9.4 [ 23 ]. According to the post-hoc power analysis, within 95% CI and alpha level is accepted as significant below than 0.05, with a total of 27 patients, we achieved over 90% power [ 23 ]. P value below than 0.05 as accepted as statistically significant. Results 27 patients completed all assessments through baseline to final assessment. Mean age and BMI were 51.59 ± 10.55 year and 28.41 ± 3.87 kg/m 2 , respectively. All patients were female, and they had no lymphedema during and the completion of the study. The great majority of patients (92.6%) were right-handed. Surgery was performed in 21 out of 27 patients. Neoadjuvant chemotherapy prior to surgery were completed in 6 patients (22.2%). More than half of the patients were treated with combined anthracycline and paclitaxel. Table 1 shows the baseline clinical characteristics of patients. Table 1 Baseline Clinical Characteristics of Patients Min Max Mean (SD) Age (year) 36 72 51.59 ± 10.55 BMI (kg/m 2 ) 21.50 36.89 28.41 ± 3.87 Chemotherapy Duration (Weeks) 12 24 17.19 ± 4.12 Type of Breast Surgery Conservative n (%) 16 (76.2) MRM n (%) 5 (23.8) ALND n (%) SLNB n (%) Axillary procedure 20 (74.1) 1 (3.7) Right n (%) Left n (%) Side of surgery 13 (61.9) 8 (38.1) Adjuvant n (%) Neoadjuvant n (%) Chemotherapy 21 (77.8) 6 (22.2) Taxane n (%) Anthyracline n (%) Chemotherapy Protocol 11 (40.7) 16 (59.3) Right n (%) Left n (%) Hand Dominance 25 (92.6) 2 (7.4) No n (%) Yes n (%) Lymphedema 27 (100) 0 (0) Handgrip strength was analyzed by mean value of the right and left sides. No significant difference was found between all time points (F (2,52) = 0.590, p = 0.558). PMS which is assessed via QF muscle strength was found significant (F (2,52) = 4.058, p = 0.023). After performing Bonferroni post-hoc test with adjustment for multiple comparisons PMS was found significant between T 1 and T 2 time points (T1: 170.38 ± 30.79 N vs 154.41 ± 23.79 N, mean difference = 15.972, p = 0.046). Handgrip and PMS values are shown in Table 2 . Table 2 Handgrip strength, peripheral muscle strength and Minnesota Manual Dexterity Test results of patients through three different time points T 1 T 2 T 3 F p n = 27 Mean ± SD Mean ± SD Mean ± SD HGS (N) 22.08 ± 3.75 22.17 ± 3.52 21.64 ± 4.03 0.590 0.558 QF (N) 170.39 ± 30.79 * 154.41 ± 23.79 * 161.35 ± 22.87 4.058 0.023 MMDT (Sec) 72.18 ± 14.60 69.68 ± 10.53 71.13 ± 11.67 0.789 0.460 HGS: Handgrip strength, QF: Quadriceps femoris, MMDT: Minnesota Manual Dexterity Test, T1: Time1, T2: Time 2, T3: Time 3, N: Newton, Sec: Second * : Bonferroni post-hoc test showed that T1 and T2 time points’ peripheral muscle strengths were found significantly different. The fine motor function which was assessed via MMDT as a time dependent manner was not found significant from baseline to final assessment (F (2,52) = 0.789, p = 0.460) (Table 2 ). Patients receiving neoadjuvant CT showed lower time in MMDT compared to patients receiving adjuvant CT after breast cancer surgery in the baseline (Mean rank 15.71 vs 8 seconds, IQR 25–75th : 62.67–76.29, z: -2.100, p = 0.036, Mann Whitney U test). The cutaneous sensory tactile function was analyzed between each pre-defined same reference point as applied gram force. Table 3 shows the gram forces in each reference point in three different assessment time points. No significant difference was found among three time points according to the Friedman test (p > 0.05). Table 3 Cutaneous sensation thresholds according to the SWMT IQR ( 25–75th ) IQR ( 25–75th ) n = 27 Reference Points 1st g 2nd g 3rd g χ 2 p Reference Points 1st g 2nd g 3rd g χ 2 p Right Hand 1 0.07–0.40 0.07–0.40 0.07–0.40 3.040 0.219 Right Foot P1 0.3175-0.40 0.07–0.40 0.40–0.40 5.607 0.061 2 0.07–0.07 0.07–0.07 0.07–0.15 0.889 0.641 P2 0.07–0.40 0.07–0.40 0.07–0.40 2.800 0.247 3 0.07–0.07 0.07–0.07 0.07–0.07 2.250 0.325 P3 0.40–0.40 0.07–0.40 0.07–0.40 0.032 0.984 4 0.07–0.07 0.07–0.40 0.07–0.07 1.118 0.572 P4 0.07–0.40 0.07–0.40 0.07–0.60 3.569 0.168 5 0.07–0.07 0.07–0.07 0.07–0.07 1.000 0.607 D1 0.07–0.40 0.07–0.40 0.07–0.40 2.462 0.292 6 0.07–0.07 0.07–0.07 0.07–0.07 0.222 0.895 D2 0.07–0.40 0.07–0.40 0.07–0.40 4.276 0.118 Left Hand 1 0.07–0.07 0.07–0.07 0.07–0.40 3.556 0.169 Left Foot P1 0.3175-0.40 0.07–0.40 0.32–0.40 0.375 0.829 2 0.07–0.07 0.07–0.07 0.07–0.07 1.000 0.607 P2 0.07–0.40 0.07–0.40 0.07–0.40 0.255 0.880 3 0.07–0.07 0.07–0.07 0.07–0.07 2.571 0.276 P3 0.40–0.40 0.32–0.40 0.40–0.40 0.745 0.689 4 0.07–0.07 0.07–0.07 0.07–0.07 1.333 0.513 P4 0.40–0.40 0.07–0.40 0.32–0.45 2.621 0.270 5 0.07–0.07 0.07–0.07 0.07–0.07 0.250 0.882 D1 0.07–0.40 0.07–0.40 0.07–0.40 2.577 0.276 6 0.07–0.40 0.07–0.15 0.07–0.07 2.333 0.311 D2 0.07–0.40 0.07–0.40 0.07–0.40 0.414 0.813 χ 2 : Non-parametric Friedman Test for Related Samples, p < 0.05, IQR: Inter quartile range, SWMT: Semmes Weinstein Monofilament Test, g: Gram Fatigue did not change significantly between T1 and T3 (z: -0.121, p = 0.904). In T3, PMS was found significantly correlated with fatigue (r=-0.636, p = 0.002). Mean handgrip strength and total chemotherapy duration were not found correlated with fatigue. CT duration tended to increase as CT protocol being as neoadjuvant according to the point-biserial correlation (r = 0.491, p = 0.011) while duration of CT seemed to be lower in patients with higher age (r=-0.516, p = 0.007). Age was not found correlated significantly with all clinical measurements except for baseline BMI (r = 0.441, p = 0.021). Discussion This pilot study showed that patients with breast cancer who underwent chemotherapy showed decreased peripheral muscle strength in the halfway of CT compared to the baseline, however, the final assessment was not significantly different from the baseline value. In addition, PMS was significantly correlated with self-reported fatigue. Cutaneous tactile sensation thresholds, fine motor function, and handgrip strength were not found significantly different in pre and post CT timeline in this patient cohort. The multifactorial nature of CIPN is still not fully understood. Some factors such as microtubule disruption as well as diminished axonal transport, changes in ion channels, neuroinflammation, oxidative stress, and mitochondrial damage are factors that are attributed to the CIPN [ 4 , 11 , 24 ]. CIPN typically shows itself in a dose-dependent manner, thereby cumulative treatment dose might cause sensory loss which is a predominant neural deficit in CIPN [ 25 , 26 ]. Paclitaxel, which is a taxane based drug, might show 100% rate of CIPN, especially in high-dose regimens. Aβ and Aδ large, myelinated fibers which are predominantly responsible for light touch and peripheral mechanoreceptors are mostly affected by this class of drugs [ 27 ]. SWMT primarily tests Aβ fibers, thereby in our study, we chose to use SWMT to detect potential CIPN related sensory changes. However, tactile detection thresholds were not found significant from baseline through the completion of the CT in all reference points in both hands and feet. This result might be attributed to the methodology of our study. Since we focus on especially in acute effects by doing the final assessment after completion of CT within seven days, cumulative effects of CT related sensory disturbances might not have manifested. Griffith et al [ 19 ] also reported no significant difference in tactile detection threshold in patients with cancer with or without CIPN. Though their study includes quite heterogeneous types of cancer as well as race and gender might be the interfering factor regarding the results. Da Silva Simão et al [ 28 ]. reported a significant difference in SWMT in patients who underwent CT, though this result can be disputable because they include patients who have already taken at least three dosages of taxanes in the baseline. In addition, their cohort comprised a relatively heterogeneous sample of cancer patients. However, no difference was found in all reference points in SWMT. This result might be attributed to not only the acute effects of CT but also that there were no other comorbidities that might contribute to the potential sensory disturbances in our patients. Nonetheless, studies reported that CIPN can manifest with even though one single high dose of CT as well as cumulative doses [ 4 ]. Studies reported that the distribution and progression of CIPN follows an ascending pattern from the distal part of the lower extremities to the proximal part of the upper extremities while symptom frequency might be generally higher in lower limbs [ 29 , 30 ]. The plantar surface of the foot is reported more susceptible to CIPN related sensorial deterioration according to the SWMT in Da Silva Simão’s study [ 28 ], yet we did not find any significant difference in terms of reference points of the plantar surface. This might be due to the factors such as rate of alcohol consumption or physical activity as well as different types of CT which were palliative in more than half of their sample. In our study, we did not use any patient-reported outcome measure related to CIPN and thus cannot conclude about the comparative efficacy of SWMT. Nonetheless, studies reported both patient-reported outcomes such as the Chemotherapy-Induced Neurotoxicity Questionnaire (CINQ) and SWMT are capable of tracking changes related to CIPN [ 31 , 32 ]. Since we aimed to assess pre-clinical CIPN and thereby we chose to use SWMT as an objective outcome. The second reason for choosing the SWMT was that the paclitaxel which was also a common protocol in our cohort is also stated as having the highest rate of CIPN and related problems mostly associated with sensorial instead of motor and autonomic [ 4 , 33 ]. Studies also stated that patient-reported outcomes can detect the effects of CIPN on daily living and quality of life instead of detecting early signs of CIPN. SWMT was stated as an effective tool to track early changes compared to the patient-reported outcomes [ 34 ]. CT agents especially anthracyclines which is frequently used in breast cancer is known as an important factor for muscle loss and depletion owing to mitochondrial damage and dysfunction associated with reactive oxygen species by which is responsible for activating proteolytic pathways such as caspase-3 and calpain, and thus result with diminished skeletal muscle mass. In addition to degradation of muscle mass related to anthracyclines, there is also reducing adenosine triphosphate synthesis is common in this drug which might create a vicious cycle of muscle loss by promoting physical inactivity and lowering activity tolerance [ 35 – 37 ]. In our study, general muscle strength which was assessed with handgrip strength was not found significant from baseline through end of CT. However, peripheral muscle strength was found significant between baseline and T2 time point which was corresponding to the completion of anthracycline in combined protocols. Our results seem in parallel with the literature findings since the great majority of our sample was treated with combined anthracycline and taxane. Yet, at the end of the CT protocol, our patients seemed to be regained their peripheral muscle strength due to no significant different was found between baseline and end of CT. However, general muscle strength did not change. This may be due to the relatively short dose duration and having no other comorbidities in our patient sample as well as there might not detect cumulative detrimental factors of CT due to relatively measuring the acute effects. Cancer related fatigue (CRF) is a major problem among patients with cancer actively undergoing CT and/or cancer survivors who completed their adjuvant neoplastic treatments. CRF is multifactorial, yet CT agents cause myotoxic effects thereby decreased muscle mass cannot generate efficient strength even for daily life activities [ 38 ]. Kilgour et al [ 39 ] stated that CRF is directly linked to muscle mass and strength in patients with advanced stage cancer. It was reported that not only peripheral but also centrally originated fatigue can cause decreased strength, however, mitigating fatigue with increased strength is inconclusive [ 40 ]. In our study, we found significant moderate to high level negative correlation between peripheral muscle strength and fatigue in at the end of CT. This result was an expected due to the cumulative effect of CT probably the major factor for weakened peripheral muscle strength as well as increased fatigue levels. Since CRF is multifactorial and might not be detected only with objective measurements due to its complex nature such as its cognitive, emotional, central, and peripheral fatigue subdimensions. Therefore, we also used European Organization for Research, Treatment of Cancer Fatigue sub-module (EORTC-FA12) which is reported as an optimal instrument for CRF [ 41 , 42 ]. We did not find a significant association between fatigue and hand grip strength in end of CT. However, literature support that our finding that no or very weak correlations were reported between handgrip strength and fatigue among cancer patients [ 41 , 43 ]. Hand function or in other words dexterity can be described as a manual skill which constitutes fine and gross motor movements in which rapid hand and eye coordination, speed and precision are required. Since these parameters are prerequisite by doing such as grasping, placing, and turning in daily life. Diminished hand function might be detrimental factor for optimal functionality. Researchers stated that hand function can be deteriorated due to some reasons related to hand such as neurological deficits or external trauma of the hand [ 21 , 44 ]. MMDT has been widely used in patients with different kind of areas such as neurological deficits, hand surgery and hand preference, industrial work performance, rehabilitation etc [ 21 , 45 ]. As far as we know, MMDT has not been used in cancer patients with or without CIPN. We chose to use turning test in MMDT in which bilateral participation of hands required. Since CIPN can affect both hands, pre-clinical CIPN may affect the performance level of MMDT. However, we did not find a significant difference among three measurement time points. Cumulative effects of CT might not be prominent in acute settings. On the other hand, having a habit of handicraft which is also common in our society among women might have also prevent the deterioration of hand function. Researchers also stated that prominent symptoms usually occur in upper extremities later than lower extremities [ 15 ]. Although, MMDT is a time dependent performance measure of hand function; participation of shoulder movements and both hands might mimic daily life activities. In addition, due to the features such as safely applicability, cheapness, and repeatability; MMDT might be an optimal choice to detect level of impairment for patients at risk for CIPN. However, in the baseline, patients who did not undergo breast cancer surgery showed significantly lower time compared to patients who underwent breast cancer surgery. This result can be expectable due to the relatively short duration between surgery and adjuvant treatment period; thus, these patients can be thought of as in still recovery process regarding pain or stiffness of the surgical side and/or axilla due to surgery. Conclusion Since CIPN has a chronic nature, it needs to be monitored closely in oncology settings not only in active treatment period but also in survivorship. Rehabilitation in oncology settings during active treatment period may provide an important insight to detect early changes related to CIPN. Thus quality of cancer care as well as preventing deteriorating effects of CIPN might be achieved [ 15 ]. In this pilot study, we aimed to show the effects of CT on motor and sensorial function. In addition, SWMT and MMDT are shown as they can be used safely and effectively in patients with breast cancer at risk for CIPN. Long term evaluation of sensorial and fine motor function with these tests may be in scope of further studies. Declarations Acknowledgements: The Authors would like to thank patients who voluntarily participated to this study during their adjuvant therapy. Author Contributions: All authors contributed to the study conception and design. Material preparation and data collection were performed by Alper Tuğral, Zeynep Arıbaş and Murat Akyol. Statistical analysis was performed by Alper Tuğral. The first draft of the manuscript was written by [Alper Tuğral, Zeynep Arıbaş and Yeşim Bakar]. All authors commented on previous versions of the manuscript and all authors read and approved the final manuscript. Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: Ethical approval was granted by Izmir Bakircay University Ethical Board of Clinical Studies with the 208/190/04032021 protocol number before enrollment of patients. Consent to participate: Informed consent has been obtained from all participating patients. References Ferlay J, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941–53. De Moor JS, et al. Cancer survivors in the United States: prevalence across the survivorship trajectory and implications for care. Cancer Epidemiol Biomarkers Prev. 2013;22(4):561–70. Cioroiu C, Weimer LH. Update on chemotherapy-induced peripheral neuropathy. Curr Neurol Neurosci Rep. 2017;17(6):47. Zajączkowska R, et al. Mechanisms of chemotherapy-induced peripheral neuropathy. Int J Mol Sci. 2019;20(6):1451. 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J Hand Ther. 2018;31(3):339–47. Weis J, et al., International psychometric validation of an EORTC quality of life module measuring cancer related fatigue (EORTC QLQ-FA12). J Natl Cancer Inst2017. 109(5). Faul F, et al. G* Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–91. Park J-H, et al. Oxaliplatin-induced peripheral neuropathy via TRPA1 stimulation in mice dorsal root ganglion is correlated with aluminum accumulation. PLoS ONE. 2015;10(4):e0124875. Park SB, et al. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA: Cancer J Clin. 2013;63(6):419–37. Tan AC, et al. Chemotherapy-induced peripheral neuropathy—patient-reported outcomes compared with NCI-CTCAE grade. Support Care Cancer. 2019;27(12):4771–7. Dougherty PM, et al. Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain. 2004;109(1–2):132–42. da Silva Simão DA, et al. Evaluation of the Semmes–Weinstein filaments and a questionnaire to assess chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2014;22(10):2767–73. Leonard GD, et al. Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer. BMC Cancer. 2005;5(1):1–10. Smith EML, et al. The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums. Cancer Nurs. 2010;33(3):173–83. Cavaletti G, et al. The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol. 2013;24(2):454–62. Driessen C, et al. Assessing the impact of chemotherapy-induced peripheral neurotoxicity on the quality of life of cancer patients. Support Care Cancer. 2012;20(4):877–81. De Iuliis F, et al. Taxane induced neuropathy in patients affected by breast cancer: literature review. Crit Rev Oncol Hematol. 2015;96(1):34–45. Lehman LF, Orsini MBP, Nicholl ARJ. The development and adaptation of the Semmes-Weinstein monofilaments in Brazil. J Hand Ther. 1993;6(4):290–7. Tarpey MD, et al. Doxorubicin causes lesions in the electron transport system of skeletal muscle mitochondria that are associated with a loss of contractile function. J Biol Chem. 2019;294(51):19709–22. Iwase T, et al., Body composition and breast cancer risk and treatment: Mechanisms and impact. Breast Cancer Res Treat, 2021: p. 1–11. Freedman RJ, et al. Weight and body composition changes during and after adjuvant chemotherapy in women with breast cancer. J Clin Endocrinol Metab. 2004;89(5):2248–53. Li C-C, Chou Y-J. and S.-C. Shun. The Relationship Between Muscle Strength and Body Composition Measures and Cancer-Related Fatigue: A Systematic Review and Meta-Analysis. Oncol Nurs Forum; 2021. Kilgour RD, et al. Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer. J Cachexia Sarcopenia Muscle. 2010;1(2):177–85. Ryan JL, et al. Mechanisms of cancer-related fatigue. Oncologist. 2007;12:22–34. Veni T, et al. Handgrip fatiguing exercise can provide objective assessment of cancer-related fatigue: a pilot study. Support Care Cancer. 2019;27(1):229–38. Meneses-Echávez JF, González-Jiménez E, Ramírez-Vélez R. Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis. BMC Cancer. 2015;15(1):1–13. Schvartsman G, et al. Could objective tests be used to measure fatigue in patients with advanced cancer? J Pain Symptom Manage. 2017;54(2):237–44. Beebe JA, Lang CE. Relationships and responsiveness of six upper extremity function tests during the first 6 months of recovery after stroke. J Neurol Phys Ther. 2009;33(2):96. Merrell G, et al. Carpal growth and function after pediatric transcarpal hand replant: case report. J Hand Surg Am. 2008;33(8):1354–7. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1419318","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":90451526,"identity":"4bc89982-3cf1-4964-9d2a-90feac53bc6e","order_by":0,"name":"Alper Tuğral","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-8017-2384","institution":"Bakırçay Üniversitesi: Bakircay Universitesi","correspondingAuthor":true,"prefix":"","firstName":"Alper","middleName":"","lastName":"Tuğral","suffix":""},{"id":90451527,"identity":"212b8cdf-efed-4282-b02b-612db1ae23f7","order_by":1,"name":"Zeynep Arıbaş","email":"","orcid":"","institution":"Bakircay University: Bakircay Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Zeynep","middleName":"","lastName":"Arıbaş","suffix":""},{"id":90451528,"identity":"d38dcce4-7bf0-4c50-8595-8ebab4e53214","order_by":2,"name":"Murat Akyol","email":"","orcid":"","institution":"Bakırçay Üniversitesi: Bakircay Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Murat","middleName":"","lastName":"Akyol","suffix":""},{"id":90451530,"identity":"0738d376-cea9-4765-bab2-49670d176b3f","order_by":3,"name":"Yeşim Bakar","email":"","orcid":"","institution":"Bakırçay Üniversitesi: Bakircay Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Yeşim","middleName":"","lastName":"Bakar","suffix":""}],"badges":[],"createdAt":"2022-03-04 13:38:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1419318/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1419318/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19256084,"identity":"40faad9d-006d-4531-a0ac-32aafe4b97c6","added_by":"auto","created_at":"2022-03-15 17:25:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":200881,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of measurement points of Semmens Weinstein Monofilament Test (SWMT). Measurements were performed both hands and feet.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-1419318/v1/d5da70de67c86f37f3b3c340.png"},{"id":21377640,"identity":"92e73324-feca-4dd1-95a2-13fa08f811d5","added_by":"auto","created_at":"2022-05-12 09:15:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":603991,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1419318/v1/4a7508a7-e7ce-4209-8562-efd9e24eb517.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eAssessing Fine Motor and Sensory Functions In Patients With Breast Cancer At Risk for Chemotherapy Induced Peripheral Neuropathy (CIPN)\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the 2018 data, World Health Organization reported that over two million new cancer cases worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Though the incidence of cancer and rates are increasing, long-term survival after cancer treatment is also increased due to the advancements in cancer treatment as well as early diagnosis. It was reported that the number of cancer survivors is expected to be over 18\u0026nbsp;million by 2022. Because of increased survivorship of cancer, short and long-term issues which affect cancer survivors in many aspects take attention in order to optimize the quality of life of them [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChemotherapy (CT) which is a common standard of care of cancer patients proven as effective, however, some CT drugs have highly deleterious neurotoxic effects which affect nerves and related structures [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Chemotherapy-induced peripheral neuropathy (CIPN) is accepted as a side effect of CT drugs which manifest predominantly sensory disturbances and ultimately result in a decrease in functional capacity and quality of life among cancer survivors. Although incidence and prevalence rates vary, it is reported as at least 40% of patients who undergo CT develops CIPN, while in some CT drugs such as taxanes, this rate might be high as 87% [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Studies reported that approximately 33% of patients develop CIPN during the CT period which may persist up to two years [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Hypersensitivity and loss of sensation can manifest as stock and glove-like distribution. Numbness, tingling, discomfort, and pain especially in the distal part of both upper and lower body are the most common symptoms who suffer from CIPN in cancer survivors. A vicious cycle of symptom aggravation might be prominent due to affected both fine and gross motor skills as well as increased risk of falling due to decreased proprioception sense [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDrugs used in CT are shown as a detrimental factor for not only sensory loss but also muscle loss. Muscle atrophy and dysfunction are attributed to diminished motor innervation while high dose corticosteroid treatment can cause mitochondrial damage of muscles. Thereby, generalized muscle weakness especially in taxanes, and related functional loss might occur [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients undergoing CT reported that there is lacking information about CIPN [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Since there has been no standardized protocol for the prevention of CIPN, detailed monitoring and guidance are needed. Proactive assessment and screening for both sensory and motor functions including fine motor skills require specific equipment and knowledge which can be performed by physical therapists [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. As mentioned above, CIPN needs continuously monitoring due to its chronic nature not only during the CT process but also during the survivorship. Thereby, we aimed to prospectively assess CIPN related motor and sensorial deviations in patients undergoing CT in this study.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis study was planned as an observational-cross sectional cohort study in a prospective longitudinal design and registered in clinical trials with the unique identification number as following: NCT04799080. All procedures and measurements in this study were performed according to 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval was granted by Izmir Bakircay University Ethical Board of Clinical Studies with the 208/190/04032021 protocol number before enrollment of patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003ePatients who applied to the medical oncology unit for systemic adjuvant or neoadjuvant chemotherapy were screened according to the predetermined inclusion and exclusion criteria. Patients who volunteered to participate in this study were initially informed about the study process and signed consent was taken for each of them. Thereafter, information of demographic and clinical features such as gender, age, diagnosis, stage, drugs, surgical, medical, and social anamnesis were gathered by a simple assessment form. Being a volunteer to participate, having been diagnosed with breast cancer, and being a candidate for CT were set as inclusion criteria. Having sensory loss due to diabetic polyneuropathy, having extensive scar tissue at hands and/or foot which may hamper assessing sensorial function, having disorders or disabilities which includes neural functional deficits such as multiple sclerosis was set as exclusion criteria.\u003c/p\u003e \u003cp\u003ePatients recruited from medical oncology unit in Izmir Bakircay University \u0026Ccedil;iğli State and Teaching Hospital. Eligible patients according to the aforementioned criteria were screened to enroll to this study. 29 Patients fulfilled the inclusion criteria; however, this pilot study was completed with a total of 27 breast cancer patients. One patient moved to another city while the other one did not fulfill the all assessments.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eAssessment Tools and Protocol\u003c/h2\u003e \u003cp\u003eThe main purpose(s) of this study was to evaluate the effect of CIPN on motor and sensory functions. Repeated measurements were set as in three different time points as following: Time 1 (T1): prior to chemotherapy, Time 2 (T2): interim time point (approx.8 weeks later) and Time 3 (T3): post-chemotherapy time point (12\u0026ndash;20 weeks later after initial assessment). The main outcome measures were set as handgrip strength, peripheral muscle strength (PMS) and Minnesota Manual Dexterity Test (MMDT) for motor function. Semmens-Weinstein Monofilament Test (SWMT) was set for sensory evaluation. Secondarily, patients' fatigue was assessed with The European Organization for Research and Treatment of Cancer Quality of Life Module Cancer Related Fatigue (EORTC-QLQ-FA12) questionnaire.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eHandgrip Strength\u003c/h2\u003e \u003cp\u003eSince CIPN usually manifest itself distally, we chose to assess motor function by measuring Hand-Grip Strength as mentioned and suggested in the literature [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Handgrip strength was 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 adducted, and hand positioned in mid-prone was used to assess hand-grip strength. The patient was asked to squeeze the dynamometer as much as she can without holding her breath and preserving her erect posture. Three measurements were requested and average of three measurements was recorded for each side. 60 seconds interval was integrated between each measurement.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePeripheral Muscle Strength\u003c/h2\u003e \u003cp\u003eReports suggest that objective motor function tests can be used in patients at risk for CIPN. In lower extremity, reduced strength was shown as correlated with increased fall risk [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thereby, we chose to assess quadriceps femoris (QF) strength which is quite important for both performing task specific functions and safe ambulation in daily life. Patients were asked to sit in an erect position while their hands are crossed in her shoulders. One of the authors (A.T) performed the manual muscle strength test bilaterally for knee extension. 3 seconds was arranged to take muscle strength and peak force was recorded as Newton (N) (Lafayette Manual Muscle Tester, Lafayette, USA). Triplicate measurements were performed for each side and average of three measurements was recorded. During the test, patients were required to preserve their erect posture without holding their breath. 60 seconds interval was integrated between each measurement.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSemmens-Weinstein Monofilament Test\u003c/h2\u003e \u003cp\u003eCutaneous sensation of patients was assessed with Semmens-Weinstein Monofilament Test (SWMT) in bilaterally palmar and plantar surface of hand, foot, and fingers in predefined reference points (Fig.\u0026nbsp;1). Patients were informed prior to testing as they must close their eyes during testing and if anything felt, it is requested to say \u0026ldquo;yes\u0026rdquo; or \u0026ldquo;I felt\u0026rdquo;. The test was started with the smallest 2.83 monofilament (0.07 gram) and three repetitions were done. Monofilaments were applied perpendicular to the site for 1.5-2 seconds and then removed. If one of them was felt by patient, cutaneous sensation was recorded as mechanical detection threshold. In case of CIPN, it is expected to be greater monofilament due to greater force is required [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eMinnesota Manual Dexterity Test\u003c/h2\u003e \u003cp\u003eHand function or dexterity, which includes both gross and fine motor movements is crucial for daily functional life. Minnesota Manual Dexterity Test (MMDT) have been used in different hand disabilities or injuries as well as to evaluate rehabilitation results of hand. MMDT was developed in early 90\u0026rsquo;s by Lafayette Instrument Company (Lafayette Instruments, Lafayette, USA). Briefly, 60 round plastic discs should be placed or removed in a board which is organized in a 4 x 15 pattern [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. One is asked to be positioned standing in front of the board. In the top right corner, which is the start point, one should grasp the disc with his/her right hand, then turn its other side and replace it with his/her left hand. This pattern is changed when his/her reach the left side of the board by grasping the disc with his/her left hand and replace it with the right hand. Although, different subtests are available such as placing or removing the discs by performed with the dominant hand or both hands; we chose to \u0026ldquo;lifting and turning\u0026rdquo; test which requires bilateral performance for both hands due to potential CIPN can affect both hands.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eFatigue Assessment\u003c/h2\u003e \u003cp\u003eThe EORTC-QLQ-FA12 questionnaire was used to assess fatigue in the pre-CT and post-CT period (T1 and T3). It assesses physical, emotional, and cognitive aspects of cancer related fatigue. The EORTC-QLQ Questionnaire and its sub-modules are the most frequently used cancer-specific health-related questionnaires. It consists of 12 items, and each is scored \u0026ldquo;1: None\u0026rdquo; through \u0026ldquo;4: A lot\u0026rdquo; according to the 4 point Likert Scoring System. Total score ranges from 0 through 100. The higher scores indicate worse quality of life or vice versa [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eSince three different time points were planned in this study design, repeated measures analysis of variance within factor (ANOVA) was used. A priori power analysis showed 54 participants are needed to be included according to the moderate level partial eta squared and effect size which are calculated by G*Power 3.1.9.4 [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. According to the post-hoc power analysis, within 95% CI and alpha level is accepted as significant below than 0.05, with a total of 27 patients, we achieved over 90% power [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. P value below than 0.05 as accepted as statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e27 patients completed all assessments through baseline to final assessment. Mean age and BMI were 51.59\u0026thinsp;\u0026plusmn;\u0026thinsp;10.55 year and 28.41\u0026thinsp;\u0026plusmn;\u0026thinsp;3.87 kg/m\u003csup\u003e2\u003c/sup\u003e, respectively. All patients were female, and they had no lymphedema during and the completion of the study. The great majority of patients (92.6%) were right-handed. Surgery was performed in 21 out of 27 patients. Neoadjuvant chemotherapy prior to surgery were completed in 6 patients (22.2%). More than half of the patients were treated with combined anthracycline and paclitaxel. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the baseline clinical characteristics of patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Clinical Characteristics of Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMax\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (year)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e51.59\u0026thinsp;\u0026plusmn;\u0026thinsp;10.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e28.41\u0026thinsp;\u0026plusmn;\u0026thinsp;3.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy Duration (Weeks)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e17.19\u0026thinsp;\u0026plusmn;\u0026thinsp;4.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of Breast Surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eConservative\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e16 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eMRM\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e5 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eALND n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSLNB n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAxillary procedure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (74.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e1 (3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRight n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e\u003cb\u003eLeft n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSide of surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e8 (38.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAdjuvant n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e\u003cb\u003eNeoadjuvant n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (77.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTaxane n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eAnthyracline n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy Protocol\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (59.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRight n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eLeft n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHand Dominance\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (92.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eYes n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphedema\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHandgrip strength was analyzed by mean value of the right and left sides. No significant difference was found between all time points (F (2,52)\u0026thinsp;=\u0026thinsp;0.590, p\u0026thinsp;=\u0026thinsp;0.558). PMS which is assessed via QF muscle strength was found significant (F (2,52)\u0026thinsp;=\u0026thinsp;4.058, p\u0026thinsp;=\u0026thinsp;0.023). After performing Bonferroni post-hoc test with adjustment for multiple comparisons PMS was found significant between T\u003csub\u003e1\u003c/sub\u003e and T\u003csub\u003e2\u003c/sub\u003e time points (T1: 170.38\u0026thinsp;\u0026plusmn;\u0026thinsp;30.79 N vs 154.41\u0026thinsp;\u0026plusmn;\u0026thinsp;23.79 N, mean difference\u0026thinsp;=\u0026thinsp;15.972, p\u0026thinsp;=\u0026thinsp;0.046). Handgrip and PMS values are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHandgrip strength, peripheral muscle strength and Minnesota Manual Dexterity Test results of patients through three different time points\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;27\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHGS (N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.08\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.17\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.64\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.590\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eQF (N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170.39\u0026thinsp;\u0026plusmn;\u0026thinsp;30.79\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154.41\u0026thinsp;\u0026plusmn;\u0026thinsp;23.79\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e161.35\u0026thinsp;\u0026plusmn;\u0026thinsp;22.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMMDT (Sec)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.18\u0026thinsp;\u0026plusmn;\u0026thinsp;14.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.68\u0026thinsp;\u0026plusmn;\u0026thinsp;10.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.13\u0026thinsp;\u0026plusmn;\u0026thinsp;11.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.460\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eHGS: Handgrip strength, QF: Quadriceps femoris, MMDT: Minnesota Manual Dexterity Test, T1: Time1, T2: Time 2, T3: Time 3, N: Newton, Sec: Second\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e\u003cem\u003e*\u003c/em\u003e\u003c/sup\u003e: \u003cem\u003eBonferroni post-hoc test showed that T1 and T2 time points\u0026rsquo; peripheral muscle strengths were found significantly different.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe fine motor function which was assessed via MMDT as a time dependent manner was not found significant from baseline to final assessment (F (2,52)\u0026thinsp;=\u0026thinsp;0.789, p\u0026thinsp;=\u0026thinsp;0.460) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Patients receiving neoadjuvant CT showed lower time in MMDT compared to patients receiving adjuvant CT after breast cancer surgery in the baseline (Mean rank 15.71 vs 8 seconds, IQR\u003csup\u003e25\u0026ndash;75th\u003c/sup\u003e: 62.67\u0026ndash;76.29, z: -2.100, p\u0026thinsp;=\u0026thinsp;0.036, Mann Whitney U test).\u003c/p\u003e \u003cp\u003eThe cutaneous sensory tactile function was analyzed between each pre-defined same reference point as applied gram force. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the gram forces in each reference point in three different assessment time points. No significant difference was found among three time points according to the Friedman test (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCutaneous sensation thresholds according to the SWMT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eIQR (\u003csup\u003e25\u0026ndash;75th\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003eIQR (\u003csup\u003e25\u0026ndash;75th\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;27\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eReference Points\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1st\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e2nd\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e3rd\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eχ\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eReference Points\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e1st\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e2nd\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e3rd\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eχ\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eRight Hand\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eRight\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eFoot\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.3175-0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.40\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e5.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.889\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.641\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.247\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.40\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.984\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.572\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e3.569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.462\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.895\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eD2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e4.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eLeft Hand\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eLeft Foot\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.3175-0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.32\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.829\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.880\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.571\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.40\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.32\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.40\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.689\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.40\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.32\u0026ndash;0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.882\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.577\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u0026ndash;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u0026ndash;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eD2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.07\u0026ndash;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003e\u003cb\u003eχ\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e: \u003cem\u003eNon-parametric Friedman Test for Related Samples, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, IQR: Inter quartile range, SWMT: Semmes Weinstein Monofilament Test, g: Gram\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFatigue did not change significantly between T1 and T3 (z: -0.121, p\u0026thinsp;=\u0026thinsp;0.904). In T3, PMS was found significantly correlated with fatigue (r=-0.636, p\u0026thinsp;=\u0026thinsp;0.002). Mean handgrip strength and total chemotherapy duration were not found correlated with fatigue.\u003c/p\u003e \u003cp\u003eCT duration tended to increase as CT protocol being as neoadjuvant according to the point-biserial correlation (r\u0026thinsp;=\u0026thinsp;0.491, p\u0026thinsp;=\u0026thinsp;0.011) while duration of CT seemed to be lower in patients with higher age (r=-0.516, p\u0026thinsp;=\u0026thinsp;0.007). Age was not found correlated significantly with all clinical measurements except for baseline BMI (r\u0026thinsp;=\u0026thinsp;0.441, p\u0026thinsp;=\u0026thinsp;0.021).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis pilot study showed that patients with breast cancer who underwent chemotherapy showed decreased peripheral muscle strength in the halfway of CT compared to the baseline, however, the final assessment was not significantly different from the baseline value. In addition, PMS was significantly correlated with self-reported fatigue. Cutaneous tactile sensation thresholds, fine motor function, and handgrip strength were not found significantly different in pre and post CT timeline in this patient cohort.\u003c/p\u003e \u003cp\u003eThe multifactorial nature of CIPN is still not fully understood. Some factors such as microtubule disruption as well as diminished axonal transport, changes in ion channels, neuroinflammation, oxidative stress, and mitochondrial damage are factors that are attributed to the CIPN [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. CIPN typically shows itself in a dose-dependent manner, thereby cumulative treatment dose might cause sensory loss which is a predominant neural deficit in CIPN [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Paclitaxel, which is a taxane based drug, might show 100% rate of CIPN, especially in high-dose regimens. Aβ and Aδ large, myelinated fibers which are predominantly responsible for light touch and peripheral mechanoreceptors are mostly affected by this class of drugs [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. SWMT primarily tests Aβ fibers, thereby in our study, we chose to use SWMT to detect potential CIPN related sensory changes. However, tactile detection thresholds were not found significant from baseline through the completion of the CT in all reference points in both hands and feet. This result might be attributed to the methodology of our study. Since we focus on especially in acute effects by doing the final assessment after completion of CT within seven days, cumulative effects of CT related sensory disturbances might not have manifested. Griffith et al [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] also reported no significant difference in tactile detection threshold in patients with cancer with or without CIPN. Though their study includes quite heterogeneous types of cancer as well as race and gender might be the interfering factor regarding the results. Da Silva Sim\u0026atilde;o et al [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. reported a significant difference in SWMT in patients who underwent CT, though this result can be disputable because they include patients who have already taken at least three dosages of taxanes in the baseline. In addition, their cohort comprised a relatively heterogeneous sample of cancer patients. However, no difference was found in all reference points in SWMT. This result might be attributed to not only the acute effects of CT but also that there were no other comorbidities that might contribute to the potential sensory disturbances in our patients. Nonetheless, studies reported that CIPN can manifest with even though one single high dose of CT as well as cumulative doses [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies reported that the distribution and progression of CIPN follows an ascending pattern from the distal part of the lower extremities to the proximal part of the upper extremities while symptom frequency might be generally higher in lower limbs [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The plantar surface of the foot is reported more susceptible to CIPN related sensorial deterioration according to the SWMT in Da Silva Sim\u0026atilde;o\u0026rsquo;s study [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], yet we did not find any significant difference in terms of reference points of the plantar surface. This might be due to the factors such as rate of alcohol consumption or physical activity as well as different types of CT which were palliative in more than half of their sample. In our study, we did not use any patient-reported outcome measure related to CIPN and thus cannot conclude about the comparative efficacy of SWMT. Nonetheless, studies reported both patient-reported outcomes such as the Chemotherapy-Induced Neurotoxicity Questionnaire (CINQ) and SWMT are capable of tracking changes related to CIPN [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Since we aimed to assess pre-clinical CIPN and thereby we chose to use SWMT as an objective outcome. The second reason for choosing the SWMT was that the paclitaxel which was also a common protocol in our cohort is also stated as having the highest rate of CIPN and related problems mostly associated with sensorial instead of motor and autonomic [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Studies also stated that patient-reported outcomes can detect the effects of CIPN on daily living and quality of life instead of detecting early signs of CIPN. SWMT was stated as an effective tool to track early changes compared to the patient-reported outcomes [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCT agents especially anthracyclines which is frequently used in breast cancer is known as an important factor for muscle loss and depletion owing to mitochondrial damage and dysfunction associated with reactive oxygen species by which is responsible for activating proteolytic pathways such as caspase-3 and calpain, and thus result with diminished skeletal muscle mass. In addition to degradation of muscle mass related to anthracyclines, there is also reducing adenosine triphosphate synthesis is common in this drug which might create a vicious cycle of muscle loss by promoting physical inactivity and lowering activity tolerance [\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In our study, general muscle strength which was assessed with handgrip strength was not found significant from baseline through end of CT. However, peripheral muscle strength was found significant between baseline and T2 time point which was corresponding to the completion of anthracycline in combined protocols. Our results seem in parallel with the literature findings since the great majority of our sample was treated with combined anthracycline and taxane. Yet, at the end of the CT protocol, our patients seemed to be regained their peripheral muscle strength due to no significant different was found between baseline and end of CT. However, general muscle strength did not change. This may be due to the relatively short dose duration and having no other comorbidities in our patient sample as well as there might not detect cumulative detrimental factors of CT due to relatively measuring the acute effects.\u003c/p\u003e \u003cp\u003eCancer related fatigue (CRF) is a major problem among patients with cancer actively undergoing CT and/or cancer survivors who completed their adjuvant neoplastic treatments. CRF is multifactorial, yet CT agents cause myotoxic effects thereby decreased muscle mass cannot generate efficient strength even for daily life activities [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Kilgour et al [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] stated that CRF is directly linked to muscle mass and strength in patients with advanced stage cancer. It was reported that not only peripheral but also centrally originated fatigue can cause decreased strength, however, mitigating fatigue with increased strength is inconclusive [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. In our study, we found significant moderate to high level negative correlation between peripheral muscle strength and fatigue in at the end of CT. This result was an expected due to the cumulative effect of CT probably the major factor for weakened peripheral muscle strength as well as increased fatigue levels. Since CRF is multifactorial and might not be detected only with objective measurements due to its complex nature such as its cognitive, emotional, central, and peripheral fatigue subdimensions. Therefore, we also used European Organization for Research, Treatment of Cancer Fatigue sub-module (EORTC-FA12) which is reported as an optimal instrument for CRF [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. We did not find a significant association between fatigue and hand grip strength in end of CT. However, literature support that our finding that no or very weak correlations were reported between handgrip strength and fatigue among cancer patients [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHand function or in other words dexterity can be described as a manual skill which constitutes fine and gross motor movements in which rapid hand and eye coordination, speed and precision are required. Since these parameters are prerequisite by doing such as grasping, placing, and turning in daily life. Diminished hand function might be detrimental factor for optimal functionality. Researchers stated that hand function can be deteriorated due to some reasons related to hand such as neurological deficits or external trauma of the hand [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. MMDT has been widely used in patients with different kind of areas such as neurological deficits, hand surgery and hand preference, industrial work performance, rehabilitation etc [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. As far as we know, MMDT has not been used in cancer patients with or without CIPN. We chose to use turning test in MMDT in which bilateral participation of hands required. Since CIPN can affect both hands, pre-clinical CIPN may affect the performance level of MMDT. However, we did not find a significant difference among three measurement time points. Cumulative effects of CT might not be prominent in acute settings. On the other hand, having a habit of handicraft which is also common in our society among women might have also prevent the deterioration of hand function. Researchers also stated that prominent symptoms usually occur in upper extremities later than lower extremities [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although, MMDT is a time dependent performance measure of hand function; participation of shoulder movements and both hands might mimic daily life activities. In addition, due to the features such as safely applicability, cheapness, and repeatability; MMDT might be an optimal choice to detect level of impairment for patients at risk for CIPN. However, in the baseline, patients who did not undergo breast cancer surgery showed significantly lower time compared to patients who underwent breast cancer surgery. This result can be expectable due to the relatively short duration between surgery and adjuvant treatment period; thus, these patients can be thought of as in still recovery process regarding pain or stiffness of the surgical side and/or axilla due to surgery.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSince CIPN has a chronic nature, it needs to be monitored closely in oncology settings not only in active treatment period but also in survivorship. Rehabilitation in oncology settings during active treatment period may provide an important insight to detect early changes related to CIPN. Thus quality of cancer care as well as preventing deteriorating effects of CIPN might be achieved [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In this pilot study, we aimed to show the effects of CT on motor and sensorial function. In addition, SWMT and MMDT are shown as they can be used safely and effectively in patients with breast cancer at risk for CIPN. Long term evaluation of sensorial and fine motor function with these tests may be in scope of further studies.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e The Authors would like to thank patients who voluntarily participated to this study during their adjuvant therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design. Material preparation and data collection were performed by Alper Tuğral, Zeynep Arıbaş and Murat Akyol. Statistical analysis was performed by Alper Tuğral. The first draft of the manuscript was written by [Alper Tuğral, Zeynep Arıbaş and Yeşim Bakar]. All authors commented on previous versions of the manuscript and all authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting\u003c/strong\u003e \u003cstrong\u003eInterests:\u003c/strong\u003e The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e\u0026nbsp; Ethical approval was granted by Izmir Bakircay University Ethical Board of Clinical Studies with the 208/190/04032021 protocol number before enrollment of patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Informed consent has been obtained from all participating patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFerlay J, et al. 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Relationships and responsiveness of six upper extremity function tests during the first 6 months of recovery after stroke. J Neurol Phys Ther. 2009;33(2):96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMerrell G, et al. Carpal growth and function after pediatric transcarpal hand replant: case report. J Hand Surg Am. 2008;33(8):1354\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, chemotherapy, Chemotherapy Induced Peripheral Neuropathy, Fatigue, Tactile sense, Peripheral muscle strength, ","lastPublishedDoi":"10.21203/rs.3.rs-1419318/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1419318/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e This study was aimed to assess potential Chemotherapy-Induced Peripheral Neuropathy (CIPN) related motor and sensorial deficits in patients with breast cancer undergoing chemotherapy. This study was registered to Clinical Trials with the following unique number: NCT04799080.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e 27 female patients (Mean age: 51.59±10.55 year) were assessed in three different time points as follows: T1 (before chemotherapy), T2 (interim analysis), and T3 (completion of chemotherapy). Motor function was assessed with handgrip strength (HGS) and peripheral muscle strength (PMS). Semmens Weinstein Monofilament Test was used to assess the potential sensory loss. Minnesota Manual Dexterity Test (MMDT) was used to assess fine motor function. Fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Module Cancer Related Fatigue (EORTC-QLQ-FA12)\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e HGS was not found significant among all three assessment time points (F (2,52) =0.590, p=0.558). PMS was found significant (F (2,52) =4.058, p=0.023). Bonferroni post-hoc test revealed that PMS was significantly decreased between T1 and T2 (170.38±30.79 N vs 154.41±23.79 N, mean difference=15.972, p=0.046, respectively). Cutaneous sensory tactile function (p\u0026gt;0.05) and MMDT (F (2,52) =0.789, p=0.460) did not change significantly from T1 through T3. In T3, fatigue and PMS was found significantly correlated (r=-0.636, p=0.002).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eCIPN related problems affect a great number of cancer survivors. Establishing knowledge and awareness associated with CIPN as well as its early recognition and detection might improve patient-centered clinical outcomes in oncology setting.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Assessing Fine Motor and Sensory Functions In Patients With Breast Cancer At Risk for Chemotherapy Induced Peripheral Neuropathy (CIPN)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-15 17:25:17","doi":"10.21203/rs.3.rs-1419318/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f27f7463-7950-4eee-be1a-140e48135d8a","owner":[],"postedDate":"March 15th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-05-12T09:15:31+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-15 17:25:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1419318","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1419318","identity":"rs-1419318","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}