Mediterranean Diet and Inequality in Early Breast Cancer
ConditionEarly Breast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorEsbjerg Hospital - University Hospital of Southern Denmark
About this trial
Social determinants such as education, income, marital status, and social networks play a crucial role in cancer outcomes, including breast cancer. One potential influencing factor is diet, and the Mediterranean diet has been shown to benefit both the health and the microbiome.
This raises the question: Does adherence to the Mediterranean diet impact the microbiome, quality of life, overall well-being, and outcomes in breast cancer patients undergoing (neo)adjuvant treatment, particularly among those with unfavorable socioeconomic determinants?
The Mediterranean diet consists of plant foods such as vegetables, fruits, nuts, seeds, berries, legumes, herbs, and spices. It also features animal proteins like fish, meat, and cheese, along with fat from olive oil. Thus, adherence to the Mediterranean diet is adherence to the official Danish diet recommendations.
This phase II clinical trial is an interdisciplinary study combining nutrition, sociology, and health research. Breast cancer patients candidates for (neo)adjuvant treatment at four oncology departments in Region South Denmark will be randomized 2:1 to the Mediterranean diet (with individual dietary guidance from a nutrition therapist aiming at daily consumption of a minimum of 30 grams of dietary fiber and weekly consumption of a minimum of 30 different plant foods; minimizing the amount of ultra-processed food) versus the patient's regular diet, in conjuction with the (neo)adjuvant chemotherapy.
The trial's primary endpoint will be changes in gut microbiota composition in feces.
The study evaluates how the Mediterranean diet affects the microbiota (evaluated using Oxford Nanopore Technology 16S sequencing on fecal samples); short-chain fatty acids in stool and plasma (assessed by mass spectrometry); immune system (using flow cytometry for immune cell determination in blood and immunohistochemical determination of immune cells in the tumor tissue); and patients' social quality of life, overall well-being, sense of empowerment, and personal feeling of agency (using the WHOQOL-100 questionnaire); taking into account the impact of the distance from the patient residence to the hospital (tracked from GEOTEAM at Statistics Denmark), and socioeconomic factors (using the DREAM database).
The evaluation of biological parameters is based on the suggested mechanism of action. A diet rich in various plant foods and dietary fiber will alter the gut microbiota, promoting bacteria producing high amounts of short-chain fatty acids. These fatty acids will activate immune cells, aiding in the destruction of cancer cells.
The study will also assess whether the Mediterranean diet will positively impact the patients' social quality of life, overall well-being, sense of empowerment, and personal feeling of agency. The Mediterranean diet may not only lead to improved dietary habits but also serve as a crucial tool for breast cancer patients, particularly among those with unfavorable socioeconomic determinants. Enhanced empowerment and improved coping tools could be an important step in combating cancer-related inequalities.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Signed written informed consent approved by the Ethical Review Board.
Age ≥ 18
Histologically confirmed unilateral adenocarcinoma of the breast, stage I-III, candidates for neoadjuvant chemotherapy followed by curative surgery, or adjuvant chemotherapy after curative surgery, according to the Danish Breast Cancer Group guidelines 48. The addition of trastuzumab and pertuzumab in HER2-positive tumors, or pembrolizumab in triple-negative tumors, per Danish Breast Cancer Group guidelines 48, is allowed as an adjunct to chemotherapy.
Good performance status (WHO performance status 0 or 1).
Disqualifiers
Clinical or radiological signs of metastatic disease.
History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin cancer.
Previous chemotherapy for cancer or other malignant disease.
Major altered digestive system disorders (e.g. gastric by-pass or Crohn's disease or ulcerative colitis)
Trial design
Design model
Parallel
Treatments tested in this trial
The goal is daily consumption of a minimum of 30 grams of dietary fiber and weekly consumption of a minimum of 30 different plant foods; minimizing the amount of ultra-processed food.
Dietary supplementThe intervention group will receive personalized education and guidance from a nutrition therapist.
Standard Diet
Other interventionThe control group will continue their normal diet, and not receive guidance or participate in group sessions.
Treatment groups
105 Participants
are divided into 2 treatment groupsGroup A: Mediterranean DietExperimental treatment 1 intervention
Group B: Standard DietActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in microbiota composition
The primary objective of this trial, assessing the clinical efficacy of the Mediterranean diet, is changes in gut microbiota composition, analyzed as microbial differential abundance (measures the difference in the abundance of specific microbial taxa between groups) by the ZicoSeq differential abundance analysis method, accounting for multiple-testing using the false discovery method (FDR). The endpoint will be measured at cycle 6 and compared with baseline values, in patients allocated to the Mediterranean Diet compared to patients on their regular diet.
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.Secondary outcomes
1
Change in alpha diversity in stool samples
Alpha diversity in stool samples, at Day 1 of chemotherapy cycle 2, 4, or 6, compared with baseline values, in the Mediterranean diet group compared to the regular diet group, to evaluate species richness and evenness within each sample. Alpha diversity will be assessed using the Shannon diversity index and tested using paired t-test.
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.2
Change in beta diversity in stool samples
Beta diversity in stool samples, at Day 1 of chemotherapy cycle 2, 4, or 6, compared with baseline values, in the Mediterranean diet group compared to the regular diet group, visualizing the differences in microbial communities between samples. Beta diversity will be assessed using Bray-Curtis dissimilarity metrics followed by Principal Coordinates Analysis for visualization and permanova for statistical inference
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.3
Level of short-chain fatty acids in stool and plasma
Level of short-chain fatty acids in stool and plasma, at Day 1 of chemotherapy cycle 2, 4, or 6, compared with baseline values, in the Mediterranean diet group compared to the regular diet group.
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.4
Quality of life measured by WHOQOL-questionnaire
Quality of life, overall well-being, and the sense of agency, at Day 1 of chemotherapy cycle 2, 4, or 6, compared with baseline values, in the Mediterranean diet group compared to the regular diet group, evaluated by the World Health Organisation Quality of Life (WHOQOL)-100 questionnaire, a comprehensive tool developed by the World Health Organization to assess various aspects of quality of life (QOL) and translated into Danish. It consists of 100 questions that cover six broad domains: physical health, psychological health, level of independence, social relationships, environment, and spirituality/religion/personal beliefs. Responses are recorded on a 5-point Likert scale, where 1 is the worst score and 5 is the best score. The mean score will be calculated for each domain and facet, with higher scores indicating a better quality of life.
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.Other outcomes
1
Level of CD4+ T-cell immune activity in blood
Level of immune activity, measured as the number of blood CD4+ T-cells from baseline to Day 1 of chemotherapy cycle 2, 4, or 6, in the two diet arms.
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.2
Level of CD8+ T-cell immune activity in blood
Level of immune activity, measured as the number of blood CD8+ T-cells from baseline to Day 1 of chemotherapy cycle 2, 4, or 6, in the two diet arms.
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.3
Level of CD 56+ Natural Killer cell immune activity in blood
Level of immune activity, measured as the number of blood CD4+ T-cells, CD8+ T-cells, or CD56+ Natural Killer cells from baseline to Day 1 of chemotherapy cycle 2, 4, or 6, in the two diet arms.
Time frame
Baseline to Day 1 of chemotherapy cycle 6. Each cycle is 3 weeks for regular schedule or 2 weeks for accelerated schedule, as per clinician decision.4
Level of CD8+ T-cell immune activity from baseline biopsy to definite surgery
Level of immune activity, measured as the number of tumor-infiltrating CD8+ T-cells from baseline biopsy to definite surgery in patients on neoadjuvant therapy, in the two diet arms.
Time frame
Baseline to date of surgery in neoadjuvant patients.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Esbjerg Hospital - University Hospital of Southern Denmark
Lead sponsor
Vejle Hospital
Collaborator
Hospital of Southern Jutland
Collaborator
Odense University Hospital
Collaborator
Syddansk Universitet, Denmark
Collaborator
University of Copenhagen
Collaborator
Aarhus University Hospital
Collaborator
Danish Breast Cancer Cooperative Group
Collaborator
Aalborg University
Collaborator
Source ClinicalTrials.gov