Breast cancer (Triple Negative and HER2+ subtypes) Cancer
Conditions
Interventions
Sample Collection & Study-Related Procedures
• Stool samples are collected at 2 time points: prior to commencing chemotherapy and after completion of chemotherapy
• Research blood samples will be coll
will be made at each clinic visit for preassessment for chemotherapy (SOC)
• Dietary assessment: The patient will complete an EPIC-Norfolk FFQ at 2 time points: prior to commencing chemotherapy and af
Sponsors
NHS Greater Glasgow and Clyde
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Unequivocal evidence of metastatic disease. 2. History of active, uncontrolled gastrointestinal (GI) disorders, including: 2.1. Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe) and Crohn’s disease (mild-moderate-severe) or indeterminate colitis 2.2. Irritable bowel syndrome (IBS) (severe or on regular medication) 2.3. Persistent infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhoea of unknown aetiology or clostridium difficile infection (recurrent) 3. Major gastrointestinal surgery with the exception of appendicectomy and cholecystectomy. Any bowel resection at any time. 4. Treatment with systemic corticosteroids (intravenous or oral) or other immunosuppressive therapy for any other condition (including but not limited to prednisolone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor [TNF] agents) within 28 days prior to Cycle 1 of neoadjuvant chemotherapy. The use of inhaled corticosteroids is allowed, as well as the use of mineralocorticoids (e.g. fludrocortisones) and low-dose supplemental corticosteroids for adrenocortical insufficiency and for orthostatic hypotension. 5. Confirmed or suspected state of immunodeficiency (primary or acquired) including HIV, hepatitis B and hepatitis C infection 6. Recent COVID-19 infection (= 28 days) or close contact with someone known to test positive (= 14 days). 7. Pregnant and/or breastfeeding individuals 8. Other severe or uncontrolled systemic disease or evidence of any other significant disorder or lab finding that makes it undesirable for the patient to participate in the study
Exclusion criteria
Exclusion criteria: 1. History of active, uncontrolled gastrointestinal (GI) disorders, including: 1.1. Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe) and Crohn’s disease (mild-moderate-severe) or indeterminate colitis 1.2. Irritable bowel syndrome (IBS) (severe or on regular medication) 1.3. Persistent infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhoea of unknown aetiology, clostridium difficile infection (recurrent) or helicobacter pylori infection (untreated) 2. Major GI surgery with the exception of appendicectomy and cholecystectomy. Any bowel resection at any time. 3. History of breast malignancy at any time or non-breast malignancy, requiring systemic therapy within the last 24 months. 4. Use of oral antibiotics within the last 6 weeks 5. Using a food exclusion diet due to diagnosis of food allergies or other food intolerances. 6. Individuals on medication requiring regular medical consultations (= 6 monthly) 7. Routine use of proprietary probiotics or prebiotics; in tablets, capsules or in powder form. 8. Recent COVID-19 infection (= 28 days) or close contact with someone known to test positive (= 14 days). 9. Pregnant and/or breastfeeding individuals 10. Other severe or uncontrolled systemic disease or evidence of any other significant disorder that makes it undesirable for the patient to participate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measured using stool samples collected at 2 time points, at baseline before commencing chemotherapy (T1) and after completion of chemotherapy but before surgery (T2) in patients. Healthy Volunteers will provide a stool sample at a single timepoint. 1. Baseline taxonomic richness for patients achieving pCR (ypT0/is ypN0) vs. non-pCR. Taxonomic richness will be calculated according to rarefied richness (other alpha diversity index measures will be explored.) 2. Stool SCFA concentration levels (acetate, butyrate and propionate) for patients achieving pCR (ypT0/is ypN0) vs. non-pCR 3. Taxon relative abundance for patients achieving pCR (ypT0/is ypN0) vs. non-pCR | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory Endpoints will be investigated using the following samples/data from patients: • Stool samples collected at 2 time points, at baseline before commencing chemotherapy (T1) and after completion of chemotherapy but before surgery (T2). • Blood samples collected at 1 time point (T1). • Dietary information collected at 2 time points (T1 and T2). • Clinical data collected at multiple time points (dependent on participants’ total number of cycles of chemotherapy received). Healthy Volunteers will provide a stool sample at a single timepoint. Exploratory Endpoints: This study will investigate the association between gut microbial composition and function and/or SCFA levels with: 1.1. Immune infiltration of tumour, utilising immunohistochemistry (IHC) and gene expression analysis 1.2. Systemic immune status with assessment of cytokines and other immune surrogate markers from peripheral blood (CRP and albumin) and stool (calprotectin) 2. The tumour-microenvironment, including IHC staining of collagen 3. Metabolomic analysis of plasma samples by Liquid Chromatography-Mass Spectrometry (LC-MS) and other techniques 4. Episodes of febrile neutropenia and/or diarrhoea (CTCAE v4.0 grading) 5. Assessment of nutritional intake utilising EPIC-Norfolk food frequency questionnaire (FFQ) at baseline. Nutritional intake will be analysed using Windiets or Nutritics software 6. Pre- and post- chemotherapy stool samples compared for patients achieving pCR (ypT0/is ypN0) vs. non-pCR 7. Other relevant pathways and markers putatively linked to pCR and the gut microbiome may also be investigated. The inferred microbial composition of healthy control samples will be used to assess dysbiosis | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactKirsty Ross
Outcome results
None listed