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Calorie restriction and reduction of breast cancer metastasis
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Calorific restriction reduces metastasis (spreading to secondary sites) of tumours in a mouse model of triple-negative breast cancer. This effect is augmented by ionising radiation. While the effect is mediated partially by reduction in expression of microRNAs, calorific restriction is likely to have many molecular targets and could form part of the therapeutic arsenal aimed at reducing triple negative breast cancer metastasis. These are the findings of a new study from researchers in Thomas Jefferson University in Philadelphia and the National Cancer Institute, NIH, Bethesda. The study is published in the journal Breast Cancer Research and Treatment.

Triple-negative breast cancer lacks oestrogen receptor, progesterone receptor and the HER2 protein. These are therapeutic targets in other forms of breast cancer and their absence makes it all the more difficult to develop effective therapies to triple-negative breast cancer. New strategies are desperately needed as this form of breast cancer features high incidence of recurrence and metastasis to sites such as the brain and lung. Calorific restriction is a form of dieting in which food intake is carefully reduced by a specified percentage and has been previously shown to induce tumour regression in mouse models of triple-negative breast cancer. The treatments given to breast cancer patients, such as hormonal therapy to reduce tumour growth and steroids to counteract chemotherapy side-effects, themselves contribute to the weight gain often experienced by women being treated for breast cancer. Too much weight has been shown to reduce the effectiveness of standard breast cancer therapies, inspiring the research team to look at metabolism and calorific restriction in women with breast cancer.

In the current study the researchers examined whether this regression was mediated by a type of small, regulatory RNA called microRNA (miR). These miRs exert their cellular effects by altering expression of other genes. The researchers examined miRarrays from mice which had been subjected to calorific restriction compared to mice which were given free access to food. The results showed that calorific restriction reduced the expression of miR-17/miR-20a. These have been previously shown to be up-regulated in patients with metastasising triple-negative breast cancer. The research team further investigated how these miRs might be regulating the response to calorific restriction. They discovered that the gene targets were related to the extracellular matrix, which would be highly relevant to tumour metastasis. Senior author Dr Nicole Simon explains the significance of this finding: “Calorie restriction promotes epigenetic changes in the breast tissue that keep the extracellular matrix strong…A strong matrix creates a sort of cage around the tumour, making it more difficult for cancer cells to escape and spread to new sites in the body."

Identification of the link to miR-17/miR-20a should be helpful in identifying triple-negative breast cancer patients whose cancer is more likely to metastasise and may suggest a potential new drug target. However, Dr Simon stresses that the effects of calorific restriction, especially when used to augment ionising radiation treatment, are likely to be more widespread than simply a targeted effect on miR-17/miR-20a. Triple negative breast cancers differ genetically between patients. Calorific restriction has the potential to ‘hit’ a large group of genes simultaneously, thus offering non-toxic benefits to patients whose cancers have different genetic bases.
To test this, Dr Simon is currently enrolling triple-negative breast cancer patients in a trial called CaReFOR (Calorie Restriction for Oncology Research). In this trial, women receiving radiation therapy for their breast cancer will also receive nutritional counselling and guidance in weight loss as they progress through their treatment.

Sources

L. Jin, et al., "The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster," Breast Cancer Research and Treatment[/u][/i]. DOI 10.1007/s10549-014-2978-7, 2014.

Press release: Thomas Jefferson University. Available at http://www.eurekalert.org/pub_releases/2...052114.php
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Calorie restriction and reduction of breast cancer metastasis00