Eating a High-fat Diet at Early Puberty may Speed up Breast Cancer Development

Researchers involved in epidemiological studies looking at the potential contributions to breast cancer risk have not been able to provided conclusive evidence linking dietary fat intake and obesity to breast cancer risk. In the pooled analysis of data from large, prospective cohort studies, high BMI (≥25 kg/m2) was a recognized risk factor for postmenopausal breast cancer [1]. Conversely, in the same analysis, high BMI (>31) is associated with reduced risk for premenopausal breast cancer. [1]

The lack of associations between dietary factors and breast cancer risk may be the result of bias. This bias may include the fact that most studies focusing on a single nutrient cannot always evaluate readily the interactive effects of other lifestyle factors. Furthermore, difficulty of dissociating fat intake from obesity, misclassification of dietary intake - including the lack of defined periods of exposure to dietary fat intake and the inability of most people to correctly measured by either food frequency questionnaires (FFQs) or diet records, estimate their usual dietary intake are among other the factors resulting in this inconsistency and lack of association.[2]


...our experimental model did not involve any weight gain from the high-fat diet…  and the results show that the culprit is the fat itself rather than weight gain...


Puberty
However, new findings show that eating a high-fat diet beginning at puberty does speed up the development of breast cancer and may actually increase the risk of cancer similar to a type often found in younger adult women. This research comes from the Breast Cancer and the Environment Research Program (BCERP) at Michigan State University, a joint effort co-funded by the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI). The research project studies the impact of prenatal-to-adult environmental exposures that predispose women to breast cancer. The study is published in the October 25, 2013 online issue of Breast Cancer Research [2].

Utilizing a preclinical model, the findings indicate that before any tumors appear, there are changes in the breast that include increased cell growth and alterations in immune cells. These changes persist into adulthood and can lead to the rapid development of precancerous lesions and ultimately breast cancer. In addition to the accelerated breast cancer development, this type of diet produces a distinct gene signature in the tumors consistent with a subset of breast cancers known as basal-like that can carry a worse prognosis.

More aggressive cancer
"This is very significant because even though the cancers arise from random mutations, the gene signature indicating a basal-like breast cancer shows the overarching and potent influence this type of diet has in the breast," noted Sandra Haslam, Ph.D, Professor of Physiology and Director, Breast Cancer and the Environment Research Center, College of Human Medicine and Michigan State University and one of the lead investigators of the project. "Cancers of this type are more aggressive in nature and typically occur in younger women. This highlights the significance of our work toward efforts against the disease," she continued.

Fat, not just weight gain
Richard C. Schwartz, PhD, Professor and Associate Dean in the College of Natural Science at the Center for Microbiology and Molecular Genetics, Michigan State University, has co-led research efforts with Haslam since 2010. "It's important to note that since our experimental model did not involve any weight gain from the high-fat diet, these findings are relevant to a much broader segment of the population than just those who are overweight," Schwartz explained. "This shows the culprit is the fat itself rather than weight gain." Early evidence indicates that the fat, which in this case was saturated animal fat, could potentially have permanent effects even if a low-fat diet is introduced later in life.

Haslam and Schwartz showed that there is a pubertal window to the promotional effects of a high fat diet (HFD) in DMBA (7,12-dimethylbenz[a]anthracene)-induced mammary mutagenesis in a BALB/c mouse model system. They concluded that the promotional effects of a high fat diet were likely caused by enhanced expression of growth factors, enhanced angiogenesis, and altered immune function.

"But," Schwartz cautioned, "This preliminary finding requires further investigation and doesn't indicate with certainty that humans will be affected in the same way. Overall, our current research indicates that avoiding excessive dietary fat of this type may help lower one's risk of breast cancer down the road. And since there isn't any evidence suggesting that avoiding this type of diet is harmful, it just makes sense to do it."

Reducing risk through education
Besides performing biomedical research, the researchers involved in the  Breast Cancer and the Environment Research Program also strives to communicate findings that can lessen the risk of breast cancer through awareness and avoidance of environmental risk factors. Haslam and Schwartz have partnered with the Michigan Breast Cancer Coalition and professors Kami Silk, PhD, Assistant Professor in the Department of Communication and the Director of the Masters in Health Communication and Sandi Smith, PhD, Director of the Health and Risk Communication Center and Professor in the Department of Communication at Michigan State University, to bring these research findings to the public.

For more information
[1] Greenwald P, Sherwood K, McDonald SS. Fat, caloric intake, and obesity: lifestyle risk factors for breast cancer. J Am Diet Assoc. 1997 Jul;97(7 Suppl):S24-30.[PubMed]
[2] Zhao Y, Tan YS, Aupperlee MD, Langohr IM, Kirk EL, Troester MA, Schwartz RC, Haslam SZ. Pubertal high fat diet: effects on mammary cancer development.Breast Cancer Res. 2013 Oct 25;15(5):R100. [Article][PubMed]
[3]Olson LK, Tan Y, Zhao Y, Aupperlee MD, Haslam SZ Pubertal exposure to high fat diet causes mouse strain-dependent alterations in mammary gland development and estrogen responsiveness. Int J Obes (Lond). 2010 Sep;34(9):1415-26. doi: 10.1038/ijo.2010.51. Epub 2010 Mar 16.[PubMed]

Photo 1 and 2: Michigan State University researchers Sandra Haslam and Richard Schwartz have discovered that a high-fat diet during puberty speeds up breast cancer development. Photo courtesy/credit: G.L. Kohuth.

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