CIPN in Early Stage Breast Cancer Patients

The QLQ-CIPN20 contains 20 items assessing sensory (9 items), motor (8 items), and autonomic symptoms (3 items). Using a 4-point Likert scale (1 = "not at all," 2 = "a little," 3 = "quite a bit," and 4 = "very much"), individuals indicate the degree to which they have experienced sensory, motor, and autonomic symptoms during the past week. Sensory raw scale scores range from 1 to 36, motor raw scale scores range from 1 to 32, and autonomic raw scale scores range from 1 to 12 for men and 1-8 for women (erectile function item is excluded). All scale scores are linearly converted to a 0-100 scale, with higher scores indicating more symptom burden.

The FACIT-Fatigue scale is a 13-item questionnaire originally designed to assess fatigue/tiredness and its impact on daily functioning in people with cancer; it has now been evaluated in other chronic diseases. Each item's response option uses a 5-point scale ranging from "not at all" to "very much." The total FACIT-Fatigue score ranges from 0 to 52, where higher scores represent less fatigue.

Participants are asked to rate the severity of each of the 20 pain domains using 0 to 10 numerical rating scales, where 0="no pain" or "not (sensation/item)" and 10="the most (descriptor) pain sensation imaginable."

The GLTEQ measures the frequency of strenuous, moderate, and mild LTPA performed for periods of 15 min or more over a usual week.

The FACT-B is a breast cancer-specific HRQoL instrument of the FACIT system. The 37-item English and (simplified) Chinese FACT-B version 4 are divided into five subscales, namely physical (PWB), social/family (SWB), emotional (EWB), functional well-beings (FWB), and the additional concerns for breast cancer (BCS). Each item is rated on a 5-point Likert scale. Negatively worded items were recoded such that a higher score indicates a better HRQoL. The FACT-B total score is the sum of scores of all five subscales.

Graded by the treating Medical Oncologist using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale. CIPN is rated from 1 to 5 depending on the severity.

Body mass will be measured to the nearest 0.1 kg using a calibrated digital scale.

Waist circumferences will be measured to the nearest 0.1 cm using a nonstretching measuring tape.

Standing height will be measured to the nearest 0.1 cm with a free-standing stadiometer

Hip circumferences will be measured to the nearest 0.1 cm using a nonstretching measuring tape.

The SPPB is a composite measure of standing balance, gait speed and chair sit-to-stand tests. The tests include: 1) the ability to stand for up to 10 seconds with feet positioned side-by-side, semi-tandem and tandem, 2) time to complete a 4-m walk at usual pace, and 3) number of sit-to-stands achieved in 30 s.

Participants walk for 10 steps, heel-to-toe, without spaces between the steps. Two trials will be performed, one with eyes open and one with eyes closed. The maximum number of consecutive steps will be recorded (maximum of 10). Errors will include taking a side step, making a space between the feet, and opening the eyes during the eyes closed trial.

Participants will squeeze an analogue hand grip dynamometer (Takei Scientific Instruments Ltd., TKK 183 5001 Grip-A, Tokyo, Japan) as hard as possible for 2-3 s. Three maximal trials will be performed on each hand, with the highest score used for analysis.

The "on-off" method will be used. The tuning fork is struck before being applied to the bony prominence situated at the dorsum of the hallux in the feet, and pollux in the hand, both just proximal to the nail bed. The patient is asked to indicate whether they feel a vibration. The patient is then asked to indicate when the vibration has stopped. One point is assigned for each vibration sensation perceived, and another point is assigned if the correct timing of the dampening of the vibration is perceived. This procedure is repeated twice on each foot and each hand. The overall score ranges from 0 to 8.

The monofilament is lightly pressed against the skin for three seconds so that it buckles into a C shape. The patient is asked to indicate whether they feel the touch. Four sites will be tested on each foot: the plantar surface of the hallux, the plantar surfaces of the first, third and fifth metatarsal heads. This will also be conducted in equivalent locations in the hand. One point is assigned for each senate site, hence, the overall score ranges from 0 to 8 for each of hands and feet.

The Tip-therm is a pen-like device with a metal cylinder on one end and a polymer cylinder on the other end. The metal side feels colder than the polymer side due to the thermal conductivity property of the material. Both ends of the device are applied to the dorsal surface of the foot between the base of the hallux and the second toe and at the dorsum of the second metacarpal in the hand between the ring and index fingers, for three seconds. The patient is asked which surface they felt was colder. One point is assigned if the correct temperature is perceived. This procedure is repeated twice on each foot and each hand, with an overall score assigned to each patient that ranges from 0 to 4 for each of hands and feet.

H-reflex and M-wave elicited in the soleus muscle. An H-reflex and M-wave recruitment curve will be plotted and changes in Hmax/Mmax and H reflex latency will be extracted.

Participants will complete the test wearing a wireless tri-axial accelerometer (Delsys, Inc). The accelerometer will be located at the level or the posterior superior iliac spine. The pen will be at the same height and record the displacement of the body by tracing a line on a sheet of paper. Participants will be asked to stand barefoot 'as still as possible without talking' for 30 seconds. This will be conducted while the patient is standing on both legs. Standing balance will be quantified as postural sway path length.

The swaymeter involves wearing a belt that will have an inflexible rod attached and a vertically mounted pen at the end of the rod. The rod will be located at the level or the posterior superior iliac spine. The pen will be at the same height and record the displacement of the body by tracing a line on a sheet of paper. Participants will be asked to stand barefoot 'as still as possible without talking' for 30 seconds. This will be conducted while the patient is standing on both legs. Standing balance will be quantified as postural sway path length.

Step counts will be noted via a pedometer and participants will be asked to keep an exercise diary.

Questions will relate to acceptability of the intervention, including barriers experienced that impacted their ability to complete the intervention, their attitudes towards exercising during chemotherapy treatment and how well they were able to integrate the exercise sessions into day/life.

Participants will be provided with a 9-Hole Peg Test kit, consisting of 9 6mm x 30mm wooden dowels and three lines of three holes (9 in total). The participants will be asked to place the wooden dowels into the holes in any order until all the holes are filled, and then immediately remove them one at a time, returning them to the container provided. This test will be done using twice using their dominant hand and twice using the non-dominant hand. For familiarisation, an additional two tests per hand will be performed in the first assessment visit.