Table 3.

Summary of exercise programs of included interventional studies

First author, year	Study design	Patients characteristics	Cancer stage and treatment type	Timing of initiating exercise	Mode	Duration (wk.)	Supervised vs. home-based	Exercise Prescription (frequency and intensity)	Type of cognitive outcome	Outcome measures	Results/hypothesis
Physical activity interventions
Hartman, 2018, 2019 [36, 38]	RCT	- 87 participants, age between 21 and 85 years old (media 57.2; SD = 10.3)	- Stage I = 61% - Stage II = 31% - Stage III = 8% - Completed chemotherapy: 51% - Undergoing Endocrine therapy = 70%	Time since surgery (30 months)  < 5 years from diagnosis	Walking	- 12 wks	Home-based	ACSM Guidelines - 10 min (60–75% MHR) to tailor personalized objective of exercise - 150 min/wk. moderate-vigorous intensity	Objective y Self-report	Cognitive Function: - NIH Toolbox - PROMIS	Of 9 examined cognitive domains, only processing speed had significantly greater improvements in the exercise group
										2º Analyses: - NIH Toolbox (Oral Symbol Digit test) - PROMIS: Anxiety, depression and fatigue	The results provided preliminary evidence about the mediating role of MVPA on perceived cognitive function when anxiety levels were reduced
Hartman, 2021 [45]	Protocol: RCT	- 250 participants, age > 40 years old	- Female breast cancer survivor in stages I, II y IIIA - Received chemotherapy or endocrine therapy	Between ≥ 6 months and up to 5 years post-active treatment	Walking (including bicycling, trekking…)	- 48 wks	Home-based	ACSM Guidelines -10 min (50–70% MHR) to tailor personalized objective of exercise - 150 min/wk. moderate-vigorous intensity	Objective y Self-report	Cognitive Function: NIH toolbox - Digit and Symbol test - PROMIS	Primary Hypothesis: the exercise group will show greater improvements in processing speed, assessed by neurocognitive testing, and self-reported cognition during the 6-month intervention Secondary Hypothesis: at 12 months, the exercise group will show greater improvements in processing speed, assessed by neurocognitive testing, and self-reported
Aerobic exercise interventions
Campbel, 2018 [16]	Pilot: RCT	- 19 participants, age between 40 and 65 years old (average 52.4; SD = 6.2), postmenopausal	- Stage II = 90% - Stage III = 10% - Received chemotherapy: AC: 22% DC: 33% FEC: 45% - Received radiotherapy Yes = 90% No = 10% - Undergoing Endocrine Therapy	Between ≥ 3 months and up to 3 years post-adjuvant treatment	Walking	- 24 wks	Supervised and home-based	ACSM Guidelines - 150 min/wk. moderate-vigorous intensity + 2 controlled session of 45 min. (60% HRR at baseline/80% HRR at 12 wks.) - 30 min. unsupervised Home-based	Objective y Self-report	Cognitive Function: -FACT-Cog ICCTF Guidelines: -HVLT-R -TMT FMRI: -The Stroop test	Except for TMT (improvements in processing speed), no significant differences were reached between the two groups
Gentry, 2018 [46]	Protocol: RCT	- 182 participants, age between 18 and 75 years old, postmenopausal	- Female breast cancer survivor in stages I, II y IIIA - Eligible to receive, but have not yet begun, Aromatase Inhibitors	4 weeks after complete radiotherapy	Walking	- 24 wks	Supervised	ACSM Guidelines - 3 day/wk - 10–15 min (2 initial wks.) - 40–45 min (remaining wks.) - Moderate-vigorous intensity (60–75% MHR at baseline; increasing according to patients)	Objective	Cognitive Function: - CANTAB - FMRI	Hypothesis: exercise will improve cognitive function in women receiving AI therapy in a domain-specific fashion such that attention, executive and memory functions will be influenced more than other domains
Northey, 2019 [37]	Pilot: RCT	- 17 participants, age between 50 and 75 years old (average 62.9 ± 7.8) Control group (CON) Moderate group (MOD) High intensity group (HIIT)	- Stage I = CON (3), MOD (1), HIIT (2) - Stage II = CON (3), MOD (4), HIIT (2) - Stage III = CON (0), MOD (0), HIIT (2) - Surgery = MOD (1) - Surgery + chemotherapy = CON (1) - Surgery + radiotherapy = CON (2), MOD (4), HIIT (3) - Surgery + radiotherapy +  - chemotherapy = CON (3), HIIT (3) - Endocrine Therapy = CON (3), MOD (2), HIIT (3)	≤ 24 months from diagnosis	Cycloergometer	- 12 wks	Supervised	-3 day/wk -36 sessions - Moderate group (MOD): 20 min (RPE: 9 y 13 Borg Scale) - High intensity group (HIIT): Initially 4 intervals of 30’ (2 min of rest), up to achieve 7 intervals 95–115 RPM (90% HR)	Objective	Cognitive Function: CogState Battery - International shopping list - Delayed recall - Groton maze learning task - One-Back test	The HIIT intervention had a positive moderate to large effect in comparison to both CON and MOD groups for aspects of cognitive performance including episodic memory, working memory, and executive function
Salerno, 2019 [39]	Randomized Crossover Trial	- 33 participants, age between 30 and 60 years old (average 49.11 ± 8)	- Stage I = 39.3% - Stage II = 35.7% - Stage III = 17.9% - Positive Estrogen Receptors = 71.4% - Surgery = 100% - Chemotherapy = 82.1% - Radiotherapy = 75% - Chemo and Radiotherapy = 90%	~ 4.5 years post-treatments	Walking	- Duration of interventions	Supervised	- Intervention 1: 30 min (moderate intensity; 8–11 Borg scale) + cognitive tasks - Intervention 2: 30 min sitting + cognitive tasks - Accelerometer (7 of MVPA)	Objective	Cognitive Function - Letter Comparison - Spatial Working Memory	The findings showed a significant interaction between time and session for reaction time in processing speed. Regarding working memory, this association showed a significant trend
Salerno, 2020 [40]	Randomized Crossover Trial	- 48 participants, age > 18 years old (average 56.02 ± 10.99)	- < Stage II = 39.6% - > Stage II = 56.2% - Received chemotherapy = 66.7% - Months since chemotherapy = 49.6% - Received radiotherapy = 66.7% - Months since radiotherapy 48.7%	~ 4.2 years from chemotherapy	Walking	- Duration of interventions	Supervised	- Intervention 1: 10 min (60% de MHR) - Intervention 2: 20 min (60% de MHR) - Intervention 3: 30 min (60% de MHR) - Rest intervention 10, 20, 30 min	Objective	Cognitive Function - Flanker Task - Spatial Working Memory - Task Switching - Letter Comparison	Patients performed significantly faster on processing speed and spatial memory working tasks post-exercise (10, 20, and 30 min.) compared to post-sitting
Combination of aerobic and resistance interventions
Galiano-Castillo, 2016; 2017 [17, 18]	RCT	- 81 participants, (age average 48.3; SD = 8.8) - Premenopausal = 10% - Postmenopausal = 90%	- Stage I = 35% - Stage II = 51% - Stage III = 14% - Chemotherapy = 5% - Radiotherapy = 5% - Chemo and radiotherapy = 90% - Undergoing Endocrine therapy	Not specified	Both aerobic and resistance training	- 8 wks	Supervised and Home-based	ACSM Guideline - 150 min/wk. moderate-vigorous intensity) or 75 min/wk. vigorous intensity) - 24 sessions - 3 sessions/wk. (90 min)	Objective and Self-report	Quality of life: - EORTC-QOL-C30	The interventions based on a home-based and tele-assisted program significantly improved the quality of life in the intervention group, which was maintained during the 6 monthly follow-up period
										2º Analyses: Cognitive Function - ACT - TMT A y B	The experimental group showed significantly higher scores in the ACT (working memory), except for TMT, which revealed no difference between groups
Witlox, 2019 [47]	Protocol: RCT	- 180 participants, age between 30 y and 75 years old	- Female breast cancer in stages I, II y III - Received neo/adjuvant chemotherapy	2–4 years post-diagnosis	Both aerobic (Nordic walking) and resistance (major muscular groups) training	- 26 wks	Supervised	Aerobic Training: - Wks. 1–4:40–60% HRR - Wks. 5–9: 15–20 m (60–70% HRR)/5–10 m (70–89% HRR) - Wks. 10–17: high intensity (10 × 30 s) - Wks. 18–26: 2 circuits of high intensity (8 × 30 s) Resistance Training - Wks. 1–9: Circuit of major muscular groups (20–25 rep./20 RM) - Wks. 10–26: 2 circuits (15–20 rep./15 RM)	Objective and Self-report	Cognitive Function - HVLT-R - ACS MDASI questionnaire - FMRI	Hypothesis: exercise training will result in changes, visible on brain MRI, such as increased brain volume (including the hippocampus), the increased connectivity of white matter, and increased perfusion

RCT Randomized Controlled Trial, ACSM American College of Sport Medicine, AC Doxorubicin y Cyclophosphamide, DC Docetaxel y Cyclophosphamide, FEC Fluorouracil, Epirubicin y Cyclophosphamide, HRR Heart Rate Reserve, FACT-Cog Functional Assessment of Cancer−Cognitive Functions, ICCTF International Cognition and Cancer Task Force, ACT Auditory Consonant Trigrams, TMT Trail Making Test, FMRI Functional Magnetic Resonance Imaging, (FMRI), EORTC-QOL-C30 The European Organization of Research and Treatment of Cancer Quality of Life Questionnaire, CANTAB Cambridge Neuropsychological Test Automated Battery, BMI Body Mass Index, MHR Maximum Heart Rate, NIH National Institute of Health, PROMIS Patient Reported Measurement Information System, RPM Revolutions Per Minute, HR Heart Rate, MVPA Moderate-Vigorous Physical Activity, RM Repetition Maximum, MDASI MD Anderson Symptom Inventory, ACS Amsterdam Cognition Scan