Is Dietary Nitrate Effective in Reducing Aerobic Glycolysis in Breast Cancer? (BEET)

Is Dietary Nitrate Effective in Reducing Aerobic Glycolysis (AG) in Breast Cancer? - A Longitudinal Study Using Specialist Magnetic Resonance (MR) Methods

Breast cancer is the most prevalent cancer affecting women, with 1 in 8 women in the UK developing breast cancer in their life time. Chemotherapy drugs, currently used for locally advanced breast cancers, are associated with side effects while dietary supplements have complex effects with a relatively small effect size. Breast tumours have different metabolism compared to healthy tissue, including elevated lactate production by aerobic glycolysis (AG), an underpinning feature of metabolism in breast cancer cells. Dietary nitrate, contained in leafy green vegetables and beetroot, has been shown to improve energy efficiency in exercising skeletal muscle, positioning itself as a disruptor of AG. The purpose of this study is to examine if dietary nitrate can disrupt AG and as a result to halt or even reverse tumour progression and survival. This study will look at scans of breast tumours using magnetic resonance imaging (MRI). Changes to tumour related biochemical substances will be measured by advanced magnetic resonance spectroscopy and changes to tissue structure will be measured by advanced diffusion MRI techniques. In this study, 16 patients undergoing surgery will be recruited for two MRI scans following a 5 day intervention programme.

In this longitudinal study, the investigators propose to examine the changes in lipid composition and microstructure in breast tumours at baseline and post dietary nitrate intervention through the applications of novel non-invasive magnetic resonance spectroscopy (MRS) methods and diffusion and lipid profiling MR imaging methods in patients. The investigators hypothesise that dietary nitrate disrupts tumour progression in breast cancer. Is there a significant difference in lipid composition in the tumour measured by MRS between baseline and post dietary nitrate intervention? Is there a significant difference in lipid composition in the whole breast tissue surrounding tumour measured by MRI between baseline and post dietary nitrate intervention? Is there a significant difference in tissue microstructure measured by MRI between baseline and post dietary nitrate intervention in the breast tissue? To assess the effect of dietary nitrate on tumour progression, paired t-tests will be performed on lipid composition measured from tumour between baseline and post intervention. To assess the effect of dietary nitrate on tumour progression, paired t-tests will be performed on lipid composition in the whole breast tissue surrounding tumour between baseline and post intervention. To assess the effect of dietary nitrate on tissue microstructure paired t-tests will be performed on water displacement measured from tumour between baseline and post intervention.

16 patients confirmed with a diagnosis of invasive ductal carcinoma who will undergo wide local excision surgery or mastectomy. All patients in the single arm will undergo a 5 day intervention drinking concentrated beetroot juice and 2 magnetic resonance imaging scan sessions pre and post intervention. MRI scan sessions will be composed of research scans including diffusion and lipid profiling MR imaging methods and MR spectroscopy (MRS) methods.

The patient will follow a 5 day dietary nitrate intervention programme, taking 3 doses of 7cl (0.4 g nitrate per dose) concentrated beetroot juice (SPORT shot, James White Drinks, Suffolk, U.K.) a day.

Inclusion Criteria: Patients with pathologically confirmed invasive ductal carcinoma (Grade 2 or 3) Undergoing wide local excision surgery or mastectomy Exclusion Criteria: Started hormone or chemotherapy treatment before recruitment. Undergoing treatment for concurrent cancer diagnosis. Taking antibiotics, proton pump or vegetable dietary supplement.

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