Physical Exercise During Preoperative Chemotherapy for Breast Cancer (Neo-ACT)

Physical Exercise During Neoadjuvant Chemotherapy for Breast Cancer as a Means to Increase Pathological Complete Response Rates: the Randomized Neo-ACT Trial

Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer. The best proof of NACT efficacy is pathological complete response (pCR), i.e. the absence of invasive tumour on post-NACT surgical histopathology. While it is known that physical exercise can help patients to better tolerate and complete often harsh cancer treatments, it is an emerging area of research to understand if and how exercise exerts anti-tumour effects and improves oncological outcomes.

The main aim of the Neo-ACT trial is to examine if a physical exercise intervention during NACT can increase pCR rates in breast cancer. Secondary aims are residual cancer burden, radiological tumour response, patient-related outcomes (health-related quality of life, physical activity), physiological outcomes (muscle strength, cardiorespiratory fitness), cancer treatment-related toxicities (cognitive dysfunction, chemotherapy completion rates) and long-term sick leave. Furthermore, the trial will explore how physical exercise affects anti-tumoral mechanisms inherent to therapy or host by hypothesis-generating translational analyses.

712 patients with primary invasive breast cancer will be randomized to either a supervised intervention of high-intensity interval and resistance training during NACT, supported by an exercise app, or to usual care, and followed for two years. Physical activity is meticulously tracked. By offering patients active involvement, the trial contributes strongly to the concept of personalized medicine.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Behavioral: Physical training

Detailed Description

The Neo-ACT assesses the primary endpoint pathological complete response (pCR) and the secondary endpoints Residual Cancer Burden (RCB), objective tumour response (RECIST), all-cause, breast cancer-specific, and recurrence-free survival at 2, 5 and 10 years, health-related quality of life assessed by the EORTC QLQ-C30 and BR23 questionnaires, self-reported physical activity (Modified Godin Leisure Time Physical activity questionnaire), toxicity-related outcomes (chemotherapy completion rates, number of unplanned hospital admissions during NACT, objective cognitive dysfunction (Amsterdam Cognition Scan), cardiac toxicity and sick leave), device-measured physical activity level (Fitbit activity tracker), muscle strength (handgrip strength test and hypothetical 1-RM maximal leg muscle strength tests), and cardiorespiratory fitness (Ekblom-Bak submaximal cycle test).

Participants randomized to the exercise group will complete 120 min exercise sessions per week from initiation of NACT to surgery (approx. five months):

• Progressive home exercise program by an individualised mobile phone application, supported by local physiotherapists
• Initial exercise intensity individually tailored to each patient's fitness at baseline and rate of perceived exertion during the program and adapted if required
• Sessions will begin with a 3-minute moderate intensity (12-13 on Borg's Rate of Perceived Exertion (RPE) scale) warm-up.

• Study Type: Interventional
• Enrollment (Estimated): 712
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jana de Boniface; Phone Number: +46702472305; Email: jana.de-boniface@ki.se
• Study Contact Backup: Name: Cecilia Haddad Ringborg; Email: cecilia.haddad.ringborg@ki.se

Study Locations

• Australia
  • Melbourne, Australia
    • Not yet recruiting
    • Cabrini Health
    • Contact: Eva Zopf
• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Hospital
    • Contact: Peeter Karihtala
  • Turku, Finland
    • Not yet recruiting
    • Turku University Hospital
    • Contact: Eeva Juhanoja
• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: Jenny Heiman; Email: jenny.heiman@vgregion.se
    • Principal Investigator: Jenny Heiman, MD, PhD
  • Lidköping, Sweden
    • Recruiting
    • Skaraborgs Sjukhus
    • Contact: Per Nyman
  • Stockholm, Sweden
    • Recruiting
    • Southern General Hospital
    • Contact: Sara Margolin
  • Stockholm, Sweden
    • Recruiting
    • Capio St Görans Hospital
    • Contact: Jana de Boniface
    • Principal Investigator: Jana de Boniface, MD, PhD
  • Sundsvall, Sweden
    • Recruiting
    • Sundsvall Hospital
    • Contact: Anna-Karin Wennstig
  • Umeå, Sweden
    • Recruiting
    • Umea University Hospital
    • Contact: Hanna Röjlar
  • Västerås, Sweden
    • Recruiting
    • Västmanlands Hospital
    • Contact: Yvette Andersson
  • Stockholm County
    • Stockholm, Stockholm County, Sweden, 17176
      • Recruiting
      • Karolinska University Hospital
      • Contact: Renske M Altena; Email: renske.altena@ki.se
      • Principal Investigator: Renske Altena
• United Kingdom
  • London, United Kingdom
    • Not yet recruiting
    • Royal Marsden
    • Contact: Marios Tasoulis
  • Scotland
    • Edinburgh, Scotland, United Kingdom
      • Not yet recruiting
      • Edinburgh Napier University
      • Contact: Frankie Brown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with primary invasive breast cancer cT1-T3 cN0-2
• Full tumour biology available before initiation of NACT
• Oral and written consent
• Age ≥ 18 years

Exclusion Criteria:

• Pregnancy or breast-feeding
• Bilateral invasive breast cancer
• The presence of musculoskeletal, neurological, respiratory, metabolic or cardiovascular conditions that may prevent safe completion of the exercise demands of the study
• Currently performing equal to or more than 150 mins of moderate to high intensity aerobic exercise and 2 sessions per week of moderate intensity resistance exercise

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard; Routine information on the benefit of physical activity
Experimental: Intervention; High-intensity interval and strength training during neoadjuvant chemotherapy	Behavioral: Physical training; Participants randomized to the exercise group will complete two structured 60-min exercise sessions per week from initiation of NACT to surgery (approx. five months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response	Absence of residual invasive tumor in breast and axilla at surgery	5-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global health-related quality of life	assessed by the EORTC QLQ-C30 questionnaire	baseline, after 1 and 2 years
Breast cancer-related quality of life	assessed by the EORTC QLQ-B23 questionnaire	baseline, after 1 and 2 years
Self-reported physical activity	Modified Godin Leisure Time Physical activity questionnaire	baseline, pre-surgery, 1- and 2-year follow-up
Chemotherapy completion rate	proportion of participants receiving the planned number of treatments	1 year
Cumulative chemotherapy dosage	total dose of NACT received to account for potential dose reduction	1 year
Objective cognitive dysfunction	online neuropsychological test (Amsterdam Cognition Scan)	baseline and 1 year
Sick leave	Patient-reported absence from work	pre-surgery and at 1- and 2-year follow-up
Device-measured physical activity level	Fit-bit tracker	baseline and 5-6months (pre surgery)
Muscle strength	hypothetical 1-RM maximal leg muscle strength test	baseline and 5-6 months
Handgrip strength	handgrip strength test	baseline and 5-6 months
Cardiorespiratory fitness	Åstrand submaximal cycle test	baseline and 5-6 months (pre-surgery)
Radiological tumour response	RECIST	5-6 months
Residual Cancer Burden (RCB)	Degree of tumor response to NACT	5-6 months

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Jana de Boniface, Karolinska Institutet

Publications and helpful links

General Publications

• de Boniface J, Altena R, Haddad Ringborg C, Bolam KA, Wengstrom Y. Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial. PLoS One. 2022 Oct 13;17(10):e0274804. doi: 10.1371/journal.pone.0274804. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: January 7, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise; Physical Conditioning, Human
• Other Study ID Numbers: Neo-ACT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be available after study completion upon reasonable request submitted to the PI and with all legal and ethical requirements being fulfilled.
• IPD Sharing Time Frame: Study protocol, SAP and ICF available on trial homepage presently. Open access. CSR and analytic code available on request, see above.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No