UK researchers observing a small group of women who followed an extreme 900 calorie a day diet found they had reduced expression of a cancer growth gene and changes in blood biomarkers for breast cancer. If these findings are confirmed in larger trials, the researchers hope they will help experts recommend specific diet changes to women at higher risk of breast cancer so they can reduce their likelihood of developing the disease.

The study was conducted by Professor Anthony Howell, Director of the Breakthrough Breast Cancer Research Unit at The University of Manchester, and his team, and was published online on 1 August in the journal Cancer Prevention Research.

Previous studies have already shown that calorie restriction, more formally termed Dietary Energy Restriction (DER), reduces the risk of spontaneous breast cancer in rats and mice, and in women who follow DER before the menopause it seems to reduce the risk of getting breast cancer after the menopause.

However, what is missing from the science is reliable markers of DER so that robust DER regimens for preventing breast cancer can be designed. So Howell and colleagues set out to investigate some DER biomarkers in breast and fat tissue and blood (serum).

For the study they recruited 19 women aged between 35 and 45 who were either overweight or obese and assessed to be at moderate risk of developing breast cancer due to family history (their lifetime risk ranged from 1 in 6 to 1 in 3).

The women were randomly assigned either to follow a DER regimen (10 participants) or continue a normal eating pattern (9 participants) of about 2,000 calories a day for one menstrual cycle.

Before and after the trial, the women underwent biopsies of breast and belly fat tissue and also gave blood and urine samples.

To look at genetic changes, Howell and colleagues extracted RNA from whole tissues and breast epithelium. To look for biomarkers, the blood and urine sample were used to generate metabolic profiles.

The results showed that:

  • Not surprisingly, DER was linked to significant reductions in weight.

  • DER was also linked to changes in serum biomarkers of breast cancer risk, including insulin, leptin (a hormonal biomarker for body fat), total and low-density (“bad”) lipoprotein cholesterol, and triglycerides (high levels of these are often linked to higher risk of a range of diseases).

  • In both breast tissue, belly tissue, and some isolated breast epithelial cells, there was evidence that genes involved in key metabolic pathways for fats and other substances (glycolytic and lipid pathways) were less active (“significantly down-regulated”).

  • This included a reduction in the expression of Stearoyl-CoA desaturase (SCD), a gene linked to cancer growth. This is the first time this has been observed in breast tissue.

Howell and colleagues concluded that:

“Reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents.”

Howell told the media that he and his team wanted to thank the women who took part in the trial:

“The women who took part in this study made a major commitment to help us carry out this vital research.”

“They enabled us to look for the first time at changes that occur within the breast tissue that may make cancer growth less likely. These results will now need to be tested in larger groups of women over longer periods of time,” he added.

Dr Alexis Willett, Head of Policy at the UK charity Breakthrough Breast Cancer, said:

“We already know that the more weight a woman gains over the course of her adult life, the higher her risk of developing breast cancer will be after she has gone through the menopause. However, it is important to find out more about how lifestyle changes like losing weight can affect breast cancer risk.”

“We wouldn’t advise women to follow a diet of this kind as those who took part were closely monitored by a specialist dietician. We recommend that women maintain a healthy weight to reduce their breast cancer risk,” added Willett.

“Biomarkers of Dietary Energy Restriction in Women at Increased Risk of Breast Cancer.”
Ong, Kai Ren, Sims, Andrew H., Harvie, Michelle, Chapman, Mary, Dunn, Warwick B., Broadhurst, David, Goodacre, Royston, Wilson, Mary, Thomas, Nicola, Clarke, Robert B., Howell, Anthony.
Cancer Prev Res 2009 2: 720-731.
Published online, August 1, 2009.
DOI: 10.1158/1940-6207.CAPR-09-0008

Sources: Manchester University.

Written by: Catharine Paddock, PhD