Breast Cancer Early Stage Breast Cancer (Stage 1-3)DIANANCT07107594

Multimodal Prehabilitation Program That Combines Physical Exercise, Psychological Intervention and Nutritional Support to Improve the Response to Neoadjuvant Chemoterhapy in Early Breast Cancer Patients

A study testing Multimodal prehabilitation in people with Breast Cancer Early Stage Breast Cancer (Stage 1-3) and Prehabilitation, run by Hospital Clinic of Barcelona at 1 site in Spain.

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Sites and contacts

Official record

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Trial summary

The aim of this clinical trial is to evaluate whether following a multimodal prehabilitation program including physical exercise, nutritional support and psychological intervention during neoadjuvant chemotherapy in breast cancer patients could improve the pathological response to chemotherapy. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer Early Stage Breast Cancer (Stage 1-3), Prehabilitation
What is being tested?: Multimodal prehabilitation
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 214 participants
Where: 1 siteSpain
Study dates: 14 Jan 2025to Mar 2028
Phase: Interventional
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically confirmed diagnosis of non-metastatic breast cancer: stages cT1-T4, cN0-N3, M0, and candidates for neoadjuvant chemotherapy (NAC).
Age ≥ 18 years.
Signed informed consent.

Who cannot join

Contraindication or physical inability to perform moderate-to-high intensity physical exercise.
Pregnant or breastfeeding patients.
Presence of other active synchronous neoplasms.
Metastatic breast cancer (stage IV).
Patients already engaging in regular physical exercise: more than 150 minutes of moderate or intense aerobic exercise per week.
Male breast cancer patients.
Personal history of a previous malignancy treated with chemotherapy.
Severe or poorly controlled psychiatric illness (including uncontrolled active substance abuse).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Helena Castillo Espín, MD contact

+34 651024667

hcastillo@clinic.cat

Eduard Mension Coll, MD, PhD contact

+34 626 20 71 71

mension@clinic.cat

Spain1 site, 1 recruiting

Hospital Clínic de Barcelona
Barcelona
Helena Castillo, M.D., PhD student, +34 932275534 ext. 5534, hcastillo@clinic.cat
Recruiting

Other trials in Spain

About this study

Official title: Multimodal Intervention During Neoadjuvant Chemotherapy in Patients With Early-breast Cancer as a Strategy to Improve Treatment Response: DIANA Trial (Multimodal Prehabilitation: DIet, ANxiety Control Psychotherapy, Physical Activity)

214 women with non-metastatic breast cancer with indication of chemotherapy before surgery will be eligible to participate. Patients will be randomly assigned to either the intervention group or the control group.

Patients assigned to the intervention group (107 women) will undergo a directed multimodal prehabilitation program during the chemotherapy (4-6 months), including structured physical exercise, psychological intervention and nutritional guidance.
Patients assigned to the control group (107 women) will undergo standard clinical management for their disease without multimodal prehabilitation.

The response to chemotherapy between the two groups will be evaluated and compared. It is expected that multimodal prehabilitation will increase the response to chemotherapy and will improve the postoperative recovery of patients and their quality of life, as well as reducing the number of complications from surgery and chemotherapy treatment. Changes in the tumor microenvironment are also expected after prehabilitation.

Read the detailed description

Breast cancer (BC) is the most common neoplasm worldwide and the leading cause of death among women. Neoadjuvant chemotherapy (NACT) is currently one of the main therapeutic pillars. The pathological response after NACT has demonstrated prognostic value in BC, being also a determinant factor for posterior treatments. In recent years, research has increasingly focused on the impact of lifestyle changes on BC, such as physical exercise, diet, and psychological interventions. These actions are part of what is known as prehabilitation, defined as the set of strategies applied prior to surgery to optimize the physical and emotional condition of patients before the surgical intervention.

The individual application of these strategies in BC patients has shown improved oncological outcomes, with positive effects on quality of life and tolerance to medical treatments. Furthermore, evidence suggests that these interventions may favorably modulate the tumor microenvironment by reducing intratumoral hypoxia, enhancing antitumor immune responses, and modulating systemic pro-inflammatory states.

Despite the demonstrated benefits of prehabilitation in multiple medical and surgical fields, there is limited evidence regarding its impact on systemic treatment outcomes in BC patients. There is also a lack of solid evidence evaluating the role of multimodal prehabilitation (combining different prehabilitation strategies) in BC, as well as its effect on treatment response and tolerance.

The current study proposes the application of a multimodal prehabilitation program during the NACT window, based on structured physical exercise, psychological therapy (mindfulness or anxiety-control techniques), and nutritional counseling in BC patients, as a strategy to enhance treatment response through changes in the tumor microenvironment. Additionally, it will be assessed whether the intervention improves treatment tolerance and postoperative recovery, among others.

The study consists of a randomized, single-blind, controlled clinical trial with two parallel groups that will include 214 women diagnosed with non-metastatic breast cancer, eligible for NACT, and awaiting surgery at our center.

Participants will be randomized into two parallel groups in a 1:1 ratio (control and intervention group, including 107 women each). A basal evaluation will be performed in all patients before starting NACT, reporting their physical, nutritional and psychological status, as well as a tumor microenvironment study in the diagnostic biopsy sample. All patients will undergo 4-6 months of NACT, the control group with standard clinical management and the intervention group following the multimodal prehabilitation program. After NACT, the physical, nutritional and psychological status of all patients will be re-evaluated. Patients will undergo surgery according to their disease and the pathological response to the treatment will be assessed.

The primary outcome will be the pathological response after NACT in both groups, assessed through the Residual Cancer Burden (RCB) index. Secondary outcomes will include NACT tolerance, quality of life, psychological and nutritional status, postoperative recovery, tumor microenvironment changes and patients' physical condition.

The group of BC patients undergoing the multimodal prehabilitation program during NACT is expected to achieve better response rates (RCB 0 and I) than the control group. Furthermore, the multimodal intervention is anticipated to promote quantitative and/or qualitative changes in the tumor microenvironment, improve NACT tolerance, enhance quality of life, and optimize postoperative recovery and the patients' physical, psychological, and nutritional status.

Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3), Prehabilitation
Being tested: Multimodal prehabilitation
Keywords: Breast cancer, Early breast cancer, Prehabilitation, Multimodal prehabilitation, Neoadjuvant chemotherapy, Lifestyle, Quality of life
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Multimodal prehabilitationBehavioural
Multimodal prehabilitation program during NACT (4-6 months) that will combine: 1) Physical exercise: cardiovascular and strength exercises designed by specialized physiotherapists, structured in 1-hour sessions twice a week. The characteristics of the activity will be adapted to the treatment phase and the physical condition of each woman. 2) Psychological therapies: standardized mindfullness practice by a specialized psychologist. As an alternative, patients who refuse mindfullness could receive psychological sessions on stress and anxiety management. 3) Nutritional counseling: periodic sessions with a specialized nutritionist providing dietary recommendations and nutritional advice adapted to the disease and condition of the patients.

Study groups in NCT07107594
Study group	Role	What they receive
Control	No intervention	107 women that will follow the standard of care. Patients in the control group will receive proper information and recommendations about lifestyle modifications according to the most recent oncological guidelines. The benefits of physical exercise, a healthy diet and psychological support will be exposed, but such interventions will not be provided in our centre.
Prehabilitation	Experimental	107 women that will follow the multimodal prehabilitation program during NACT (physical exercise, psychological intervention, nutritional support). Receives: Behavioral: Multimodal prehabilitation

What is being measured

The primary outcome is the main question the study is designed to answer.

Residual Cancer Burden Index (RCB)
The main variable of the trial is the RCB index score, obtained from the histological specimen of the oncological surgery performed after NAC. The four levels of response of the RCB index (RCB 0, I, II and III) will be divided into a favorable profile of response (fRCB), that will include cathegories RCB 0 and I, and an unfavorable response profile (uRCB), including RCB II and III.
It is estimated that the average rate of a favorable RCB (fRCB) score, including RCB 0 and RCB I, will be approximately 40% in the control arm. Parallelly, the expected rates of unfavorable RCB (uRCB) scores, including RCB II and RCB III, are 60%. The objective is to improve the response rates by 20% in the intervention group, with 60% of fRCB scores and 40% of uRCB scores in this group.
Measured: From enrollment (baseline, day 1) until the end of treatment at 4-6 months (preoperative).

Secondary outcomes (23)

Tumor microenvironment (Gene expression analyses)
Formalin fixed-paraffin embedded tumor tissue blocks will be analyzed by hematoxylin and eosin staining, to check tumor surface area. Samples with ≥20% of tumor cells will be selected for RNA extraction. The High Pure FFPET RNA Isolation Kit (Roche) will purify RNA from FFPE tumor samples. A minimum of ∼100 ng of total RNA will be used to measure the expression of 185 breast cancer-related and immune-related genes including the genes of PAM50 and HER2DX and 7 housekeeping genes using the nCounter platform (Nanostring Technologies, Seattle, USA). The gene expression for each sample will be independently normalized to the geometric mean of housekeeping genes. The 14-gene immunoglobulin (IGG) signature (i.e., CD27, CD79A, HLA-C, IGJ, IGKC, IGL, IGLV3-25, IL2RG, CXCL8, LAX1, NTN3, PIM2, POU2AF1 and TNFRSF17) will be calculated.
Measured: From enrollment (baseline, day 1) until the end of treatment at 4-6 months (postoperative).
Tumor staging
Registered according to the TNM system by the. American Joint Committee on Cancer (AJCC) 8th edition
Measured: At diagnosis or day 1 (clinical TNM or cTNM) and after surgery (pathological TNM or pTNM)
Tumor cellularity after NACT
Reported as the percentage (%) of neoplastic cells in the surgical specimen.
Measured: After the surgery (after NACT, 4-6 months from day 1)
Assessment of vascular density in peritumoral areas
The assessment will involve evaluating microvascular density through immunohistochemical staining for CD31 on tumor or tumor bed sections. This evaluation follows a two-step process:
1. Hotspot Area Selection: Identification of hotspot areas under a light microscope at 4x magnification.
2. Manual Counting: Manual counting of all vascular lumens in the selected field at 20x magnification.
This method ensures precise quantification of vascular density in both the peritumoral and tumor bed regions.
Measured: At enrollment (baseline, day 1) and at the end of treatment at 4-6 months (postoperative).
Adverse effects of neoadjuvant chemotherapy
They will be recorded by the research team and classified according to the CTCAE (Common Terminology Criteria for Adverse Events) version 5.0. Data will be collected at the end of NAC in both groups.
Measured: After the treatment (4-6 months later, presurgical).
Chemotherapy completion rate
The proportion of patients who received the full course of chemotherapy with the corresponding dose. This will be evaluated before surgery in both groups.
Measured: At the end of the treatment (4-6 months after day 1, preoperative)
Hospitalization during NACT
Need for hospitalization during neoadjuvant chemotherapy: the number of hospital admissions prior to surgery will be recorded as an absolute count.
Measured: At the end of the treatment (4-6 months after day 1, preoperative)
Post-surgical hospitalization
Length of hospitalization after oncological surgery: Measured in days.
Measured: From the surgery (5-7 months after day 1) until 30 days after the operation.
Pain control after oncological surgery
Pain will be assessed using the Visual Analogue Scale (VAS) during the hospital stay. The scale ranges from 0 to 10, with higher scores indicating greater pain severity.
Measured: Since the surgery is done (5-7 months from day 1) until hospital discharge.
Post-operative complications
These will be classified based on timing as immediate postoperative complications (during the procedure or within 24 hours), early complications (up to 7 days post-surgery), and late postoperative complications (from 7 to 30 days post-surgery). Severity will be recorded using the Clavien-Dindo scale.
Emergency visits and readmissions will also be reported: The absolute number, reasons, and length of hospital stay will be recorded up to 30 days post-surgery.
Measured: From the surgery (5-7 months from day 1) until 30 days after.
Weight
Weight in kilograms will be registered before and after NACT
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after surgery.
Body Mass Index
Body mass index (BMI) will be measured before and after chemotherapy (kg/m2)
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after surgery.
Physical activity level
The international questionnaire of Physical Activity (IPAQ) will be used to register the level of physical activity of the subjects. Minimum score: 0 MET-min/week. Maximum score: no formal upper limit (normally 20,000 MET-min/week). According to the punctuation, the level of physical activity can be classified into low (< 600 MET-min/week), moderate (≥ 600 and < 3,000 MET-min/week) or high (≥ 3,000 MET-min/week).
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.
Strength
Assessed through the hand grip strength test, using a hand-held dynamometer (measured in kilograms).
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.
Estimated maximal oxygen uptake (VO2 max)
To evaluate the general physical status of patients (as an estimate of VO₂), the 30-Second Sit-to-Stand Test will be performed and recorded as an absolute number.
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.
Change in oxygen consumption (VO2) from baseline to post-neoadjuvant therapy
Through a Cardiopulmonary Exercise Testing (CPET), the oxygen consumption will be measured in all patients (ml/kg/min) before and after finishing neoadjuvant chemotherapy.
Measured: Before the chemotherapy (baseline or day 1) and after the treatment (4-6 months later, presurgical).
Patient-perceived quality of life
Measured using the EORTC QLQ-30 questionnaire (0-100 points: higher scores on functional scales and the global health status scale indicate better functioning and quality of life, while higher scores on symptom scales indicate a higher level of symptoms).
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.
Anxiety and Depression levels
Assessed using the Hospital Anxiety and Depression Scale (HADS), which score ranges from 0 to 21 points. Higher scores indicate more severe symptoms of anxiety or depression: 0-7: Normal or no significant anxiety/depression, 8-10: Mild anxiety/depression, 11-15: Moderate anxiety/depression, 16-21: Severe anxiety/depression.
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.
Mindfulness status
Assessed through the Five Facet Mindfulness Questionnaire (FFMQ). Score 39 - 195 points. A higher score indicates a greater level of mindfulness.
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.
Nutritional status
Complete blood analysis: Including liver and renal profile, blood count, ionogram, albumin, prealbumin, glucose, interleukin-6 and IGF-1.
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after the surgery.
Adherence to mediterranean diet
Validated Questionnaire of Mediterranean Diet Adherence (MEDAS-14). Scoring: 0-14 points. Higher scores mean higher adherence to Mediterranean diet, being a score equal or superior to 9 considered a good adherence to such diet.
Measured: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.
Prehabilitation program adherence
Measured by the number of sessions attended relative to the scheduled sessions.
Measured: After the prehabilitation program (4-6 months from day 1, presurgical).
Body image perception
Assessment of how patients perceive and feel about their physical appearance after the finalization of breast cancer treatments through the validated questionnaire Body Image Scale Questionnaire (BIS).
Measured: 1 year after the surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Jan 2025Mar 2028

First posted6 Aug 2025
Study start14 Jan 2025
Primary completionJan 2028 (estimated)
Study completionMar 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (17)Papers the sponsor has linked to this study.
Other trials for Breast Cancer Early Stage Breast Cancer (Stage 1-3)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 214 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07107594
Sponsor's protocol ID: HCB/2023/1036
Acronym: DIANA
Status last verified: Jan 2026
First submitted: 6 Jul 2025
Last updated: 15 Jan 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Individual participant data will not be shared due to privacy concerns and ethical restrictions related to the confidentiality of patient information. The informed consent obtained from participants does not include provisions for data sharing beyond the primary research team.

Publications

Angelats L, Pare L, Rubio-Perez C, Sanfeliu E, Gonzalez A, Segui E, Villacampa G, Marin-Aguilera M, Pernas S, Conte B, Albarran-Fernandez V, Martinez-Saez O, Aguirre A, Galvan P, Fernandez-Martinez A, Cobo S, Rey M, Martinez-Romero A, Walbaum B, Schettini F, Vidal M, Buckingham W, Munoz M, Adamo B, Agrawal Y, Guedan S, Pascual T, Agudo J, Grzelak M, Borcherding N, Heyn H, Vivancos A, Parker JS, Villagrasa P, Perou CM, Prat A, Braso-Maristany F. Linking tumor immune infiltration to enhanced longevity in recurrence-free breast cancer. ESMO Open. 2025 Jan;10(1):104109. doi: 10.1016/j.esmoop.2024.104109. Epub 2025 Jan 6.
PubMed 39765189
Toohey K, Hunter M, McKinnon K, Casey T, Turner M, Taylor S, Paterson C. A systematic review of multimodal prehabilitation in breast cancer. Breast Cancer Res Treat. 2023 Jan;197(1):1-37. doi: 10.1007/s10549-022-06759-1. Epub 2022 Oct 21.
PubMed 36269525
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, Schmitt WD, Blohmer JU, Karn T, Pfitzner BM, Kummel S, Engels K, Schneeweiss A, Hartmann A, Noske A, Fasching PA, Jackisch C, van Mackelenbergh M, Sinn P, Schem C, Hanusch C, Untch M, Loibl S. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018 Jan;19(1):40-50. doi: 10.1016/S1470-2045(17)30904-X. Epub 2017 Dec 7.
PubMed 29233559
Valenza C, Taurelli Salimbeni B, Santoro C, Trapani D, Antonarelli G, Curigliano G. Tumor Infiltrating Lymphocytes across Breast Cancer Subtypes: Current Issues for Biomarker Assessment. Cancers (Basel). 2023 Jan 26;15(3):767. doi: 10.3390/cancers15030767.
PubMed 36765724
Wiggins JM, Opoku-Acheampong AB, Baumfalk DR, Siemann DW, Behnke BJ. Exercise and the Tumor Microenvironment: Potential Therapeutic Implications. Exerc Sport Sci Rev. 2018 Jan;46(1):56-64. doi: 10.1249/JES.0000000000000137.
PubMed 29166299
van Waart H, Stuiver MM, van Harten WH, Geleijn E, Kieffer JM, Buffart LM, de Maaker-Berkhof M, Boven E, Schrama J, Geenen MM, Meerum Terwogt JM, van Bochove A, Lustig V, van den Heiligenberg SM, Smorenburg CH, Hellendoorn-van Vreeswijk JA, Sonke GS, Aaronson NK. Effect of Low-Intensity Physical Activity and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on Physical Fitness, Fatigue, and Chemotherapy Completion Rates: Results of the PACES Randomized Clinical Trial. J Clin Oncol. 2015 Jun 10;33(17):1918-27. doi: 10.1200/JCO.2014.59.1081. Epub 2015 Apr 27.
PubMed 25918291
Cannioto RA, Hutson A, Dighe S, McCann W, McCann SE, Zirpoli GR, Barlow W, Kelly KM, DeNysschen CA, Hershman DL, Unger JM, Moore HCF, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Albain KS, Budd GT, Ambrosone CB. Physical Activity Before, During, and After Chemotherapy for High-Risk Breast Cancer: Relationships With Survival. J Natl Cancer Inst. 2021 Jan 4;113(1):54-63. doi: 10.1093/jnci/djaa046.
PubMed 32239145
Peterson LL, Ligibel JA. Physical Activity and Breast Cancer: an Opportunity to Improve Outcomes. Curr Oncol Rep. 2018 Apr 30;20(7):50. doi: 10.1007/s11912-018-0702-1.
PubMed 29713835
Ochoa-Arnedo C, Prats C, Travier N, Marques-Feixa L, Flix-Valle A, de Frutos ML, Domingo-Gil E, Medina JC, Serra-Blasco M. Stressful Life Events and Distress in Breast Cancer: A 5-Years Follow-Up. Int J Clin Health Psychol. 2022 May-Aug;22(2):100303. doi: 10.1016/j.ijchp.2022.100303. Epub 2022 Apr 1.
PubMed 35572072
Oh PJ, Shin SR, Ahn HS, Kim HJ. Meta-analysis of psychosocial interventions on survival time in patients with cancer. Psychol Health. 2016;31(4):396-419. doi: 10.1080/08870446.2015.1111370. Epub 2015 Dec 18.
PubMed 26518363
Andersen BL, Yang HC, Farrar WB, Golden-Kreutz DM, Emery CF, Thornton LM, Young DC, Carson WE 3rd. Psychologic intervention improves survival for breast cancer patients: a randomized clinical trial. Cancer. 2008 Dec 15;113(12):3450-8. doi: 10.1002/cncr.23969.
PubMed 19016270
Chen Y, Ahmad M. Effectiveness of adjunct psychotherapy for cancer treatment: a review. Future Oncol. 2018 Jun;14(15):1487-1496. doi: 10.2217/fon-2017-0671. Epub 2018 May 16.
PubMed 29767550
Tommasi C, Balsano R, Coriano M, Pellegrino B, Saba G, Bardanzellu F, Denaro N, Ramundo M, Toma I, Fusaro A, Martella S, Aiello MM, Scartozzi M, Musolino A, Solinas C. Long-Term Effects of Breast Cancer Therapy and Care: Calm after the Storm? J Clin Med. 2022 Dec 6;11(23):7239. doi: 10.3390/jcm11237239.
PubMed 36498813
Santa Mina D, Brahmbhatt P, Lopez C, Baima J, Gillis C, Trachtenberg L, Silver JK. The Case for Prehabilitation Prior to Breast Cancer Treatment. PM R. 2017 Sep;9(9S2):S305-S316. doi: 10.1016/j.pmrj.2017.08.402.
PubMed 28942905
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14.
PubMed 24529560

Interested in taking part?

Helena Castillo Espín, MD

+34 651024667

hcastillo@clinic.cat

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multimodal Intervention During Neoadjuvant Chemotherapy in Patients With Early-breast Cancer as a Strategy to Improve Treatment Response: DIANA Trial (Multimodal Prehabilitation: DIet, ANxiety Control Psychotherapy, Physical Activity)
ClinicalTrials.gov ID: NCT07107594
Acronym / sponsor ID: DIANA / HCB/2023/1036
Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3), Prehabilitation
Keywords: Breast cancer, Early breast cancer, Prehabilitation, Multimodal prehabilitation, Neoadjuvant chemotherapy, Lifestyle, Quality of life
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 214 participants (estimated)
Lead sponsor: Hospital Clinic of BarcelonaUniversity, hospital or other
Collaborators: Fundació La Marató de TV3
Study start: 14 Jan 2025 (actual)
Primary completion: Jan 2028 (estimated)
Study completion: Mar 2028 (estimated)
First posted: 6 Aug 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Patients assigned to the intervention group (107 women) will undergo a directed multimodal prehabilitation program during the chemotherapy (4-6 months), including structured physical exercise, psychological intervention and nutritional guidance.
Patients assigned to the control group (107 women) will undergo standard clinical management for their disease without multimodal prehabilitation.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Control	No intervention	–107 women that will follow the standard of care. Patients in the control group will receive proper information and recommendations about lifestyle modifications according to the most recent oncological guidelines. The benefits of physical exercise, a healthy diet and psychological support will be exposed, but such interventions will not be provided in our centre.
Prehabilitation	Experimental	Behavioral: Multimodal prehabilitation107 women that will follow the multimodal prehabilitation program during NACT (physical exercise, psychological intervention, nutritional support).

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Histologically confirmed diagnosis of non-metastatic breast cancer: stages cT1-T4, cN0-N3, M0, and candidates for neoadjuvant chemotherapy (NAC).
Age ≥ 18 years.
Signed informed consent.

Key exclusion criteria (8 listed)

Contraindication or physical inability to perform moderate-to-high intensity physical exercise.
Pregnant or breastfeeding patients.
Presence of other active synchronous neoplasms.
Metastatic breast cancer (stage IV).
Patients already engaging in regular physical exercise: more than 150 minutes of moderate or intense aerobic exercise per week.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Multimodal prehabilitationMultimodal prehabilitation program during NACT (4-6 months) that will combine: 1) Physical exercise: cardiovascular and strength exercises designed by specialized physiotherapists, structured in 1-hour sessions twice a week. The characteristics of the activity will be adapted to the treatment phase and the physical condition of each woman. 2) Psychological therapies: standardized mindfullness practice by a specialized psychologist. As an alternative, patients who refuse mindfullness could receive psychological sessions on stress and anxiety management. 3) Nutritional counseling: periodic sessions with a specialized nutritionist providing dietary recommendations and nutritional advice adapted to the disease and condition of the patients.	Behavioural	Prehabilitation

Primary outcome

Residual Cancer Burden Index (RCB)
Time frame: From enrollment (baseline, day 1) until the end of treatment at 4-6 months (preoperative).
The main variable of the trial is the RCB index score, obtained from the histological specimen of the oncological surgery performed after NAC. The four levels of response of the RCB index (RCB 0, I, II and III) will be divided into a favorable profile of response (fRCB), that will include cathegories RCB 0 and I, and an unfavorable response profile (uRCB), including RCB II and III. It is estimated that the average rate of a favorable RCB (fRCB) score, including RCB 0 and RCB I, will be approximately 40% in the control arm. Parallelly, the expected rates of unfavorable RCB (uRCB) scores, including RCB II and RCB III, are 60%. The objective is to improve the response rates by 20% in the intervention group, with 60% of fRCB scores and 40% of uRCB scores in this group.

23 secondary outcomes

Tumor microenvironment (Gene expression analyses)
Time frame: From enrollment (baseline, day 1) until the end of treatment at 4-6 months (postoperative).
Tumor staging
Time frame: At diagnosis or day 1 (clinical TNM or cTNM) and after surgery (pathological TNM or pTNM)
Tumor cellularity after NACT
Time frame: After the surgery (after NACT, 4-6 months from day 1)
Assessment of vascular density in peritumoral areas
Time frame: At enrollment (baseline, day 1) and at the end of treatment at 4-6 months (postoperative).
Adverse effects of neoadjuvant chemotherapy
Time frame: After the treatment (4-6 months later, presurgical).
Chemotherapy completion rate
Time frame: At the end of the treatment (4-6 months after day 1, preoperative)
Hospitalization during NACT
Time frame: At the end of the treatment (4-6 months after day 1, preoperative)
Post-surgical hospitalization
Time frame: From the surgery (5-7 months after day 1) until 30 days after the operation.
Pain control after oncological surgery
Time frame: Since the surgery is done (5-7 months from day 1) until hospital discharge.
Post-operative complications
Time frame: From the surgery (5-7 months from day 1) until 30 days after.
Weight
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after surgery.
Body Mass Index
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after surgery.
Physical activity level
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.
Strength
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.
Estimated maximal oxygen uptake (VO2 max)
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.
Change in oxygen consumption (VO2) from baseline to post-neoadjuvant therapy
Time frame: Before the chemotherapy (baseline or day 1) and after the treatment (4-6 months later, presurgical).
Patient-perceived quality of life
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.
Anxiety and Depression levels
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.
Mindfulness status
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.
Nutritional status
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after the surgery.
Adherence to mediterranean diet
Time frame: Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.
Prehabilitation program adherence
Time frame: After the prehabilitation program (4-6 months from day 1, presurgical).
Body image perception
Time frame: 1 year after the surgery

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
Background: PubMed 39765189Angelats L, Pare L, Rubio-Perez C, Sanfeliu E, Gonzalez A, Segui E, Villacampa G, Marin-Aguilera M, Pernas S, Conte B, Albarran-Fernandez V, Martinez-Saez O, Aguirre A, Galvan P, Fernandez-Martinez A, Cobo S, Rey M, Martinez-Romero A, Walbaum B, Schettini F, Vidal M, Buckingham W, Munoz M, Adamo B, Agrawal Y, Guedan S, Pascual T, Agudo J, Grzelak M, Borcherding N, Heyn H, Vivancos A, Parker JS, Villagrasa P, Perou CM, Prat A, Braso-Maristany F. Linking tumor immune infiltration to enhanced longevity in recurrence-free breast cancer. ESMO Open. 2025 Jan;10(1):104109. doi: 10.1016/j.esmoop.2024.104109. Epub 2025 Jan 6.
Background: PubMed 36269525Toohey K, Hunter M, McKinnon K, Casey T, Turner M, Taylor S, Paterson C. A systematic review of multimodal prehabilitation in breast cancer. Breast Cancer Res Treat. 2023 Jan;197(1):1-37. doi: 10.1007/s10549-022-06759-1. Epub 2022 Oct 21.
Background: PubMed 29233559Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, Schmitt WD, Blohmer JU, Karn T, Pfitzner BM, Kummel S, Engels K, Schneeweiss A, Hartmann A, Noske A, Fasching PA, Jackisch C, van Mackelenbergh M, Sinn P, Schem C, Hanusch C, Untch M, Loibl S. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018 Jan;19(1):40-50. doi: 10.1016/S1470-2045(17)30904-X. Epub 2017 Dec 7.
Background: PubMed 36765724Valenza C, Taurelli Salimbeni B, Santoro C, Trapani D, Antonarelli G, Curigliano G. Tumor Infiltrating Lymphocytes across Breast Cancer Subtypes: Current Issues for Biomarker Assessment. Cancers (Basel). 2023 Jan 26;15(3):767. doi: 10.3390/cancers15030767.
Background: PubMed 29166299Wiggins JM, Opoku-Acheampong AB, Baumfalk DR, Siemann DW, Behnke BJ. Exercise and the Tumor Microenvironment: Potential Therapeutic Implications. Exerc Sport Sci Rev. 2018 Jan;46(1):56-64. doi: 10.1249/JES.0000000000000137.
Background: PubMed 25918291van Waart H, Stuiver MM, van Harten WH, Geleijn E, Kieffer JM, Buffart LM, de Maaker-Berkhof M, Boven E, Schrama J, Geenen MM, Meerum Terwogt JM, van Bochove A, Lustig V, van den Heiligenberg SM, Smorenburg CH, Hellendoorn-van Vreeswijk JA, Sonke GS, Aaronson NK. Effect of Low-Intensity Physical Activity and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on Physical Fitness, Fatigue, and Chemotherapy Completion Rates: Results of the PACES Randomized Clinical Trial. J Clin Oncol. 2015 Jun 10;33(17):1918-27. doi: 10.1200/JCO.2014.59.1081. Epub 2015 Apr 27.
Background: PubMed 32239145Cannioto RA, Hutson A, Dighe S, McCann W, McCann SE, Zirpoli GR, Barlow W, Kelly KM, DeNysschen CA, Hershman DL, Unger JM, Moore HCF, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Albain KS, Budd GT, Ambrosone CB. Physical Activity Before, During, and After Chemotherapy for High-Risk Breast Cancer: Relationships With Survival. J Natl Cancer Inst. 2021 Jan 4;113(1):54-63. doi: 10.1093/jnci/djaa046.
Background: PubMed 29713835Peterson LL, Ligibel JA. Physical Activity and Breast Cancer: an Opportunity to Improve Outcomes. Curr Oncol Rep. 2018 Apr 30;20(7):50. doi: 10.1007/s11912-018-0702-1.
Background: PubMed 35572072Ochoa-Arnedo C, Prats C, Travier N, Marques-Feixa L, Flix-Valle A, de Frutos ML, Domingo-Gil E, Medina JC, Serra-Blasco M. Stressful Life Events and Distress in Breast Cancer: A 5-Years Follow-Up. Int J Clin Health Psychol. 2022 May-Aug;22(2):100303. doi: 10.1016/j.ijchp.2022.100303. Epub 2022 Apr 1.
Background: PubMed 26518363Oh PJ, Shin SR, Ahn HS, Kim HJ. Meta-analysis of psychosocial interventions on survival time in patients with cancer. Psychol Health. 2016;31(4):396-419. doi: 10.1080/08870446.2015.1111370. Epub 2015 Dec 18.
Background: PubMed 19016270Andersen BL, Yang HC, Farrar WB, Golden-Kreutz DM, Emery CF, Thornton LM, Young DC, Carson WE 3rd. Psychologic intervention improves survival for breast cancer patients: a randomized clinical trial. Cancer. 2008 Dec 15;113(12):3450-8. doi: 10.1002/cncr.23969.
Background: PubMed 29767550Chen Y, Ahmad M. Effectiveness of adjunct psychotherapy for cancer treatment: a review. Future Oncol. 2018 Jun;14(15):1487-1496. doi: 10.2217/fon-2017-0671. Epub 2018 May 16.
Breast cancer statisticsLink provided by the sponsor.
Individual participant dataSharing planned: No. Individual participant data will not be shared due to privacy concerns and ethical restrictions related to the confidentiality of patient information. The informed consent obtained from participants does not include provisions for data sharing beyond the primary research team.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Helena Castillo Espín, MD contact

+34 651024667

hcastillo@clinic.cat

Eduard Mension Coll, MD, PhD contact

+34 626 20 71 71

mension@clinic.cat

Berta Díaz-Feijoo, MD, PhD study director

Hospital Clinic of Barcelona

Eduard Mension Coll, MD, PhD study director

Hospital Clinic of Barcelona

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Multimodal prehabilitation in people with Breast Cancer Early Stage Breast Cancer (Stage 1-3) and Prehabilitation, run by Hospital Clinic of Barcelona at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Helena Castillo Espín, MD (+34 651024667, hcastillo@clinic.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Residual Cancer Burden Index (RCB) (time frame: From enrollment (baseline, day 1) until the end of treatment at 4-6 months (preoperative).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07107594, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2026.