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 . 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  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 . 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 .
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 , 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 .
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 . Kilgour et al  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 . 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 . 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.