Making Sense of the Soy-Genistein-Her2 Breast Cancer Connection

Making Sense of the Soy-Genistein-Her2 Breast Cancer Connection

February 13, 2013

The impact of soy on breast cancer is puzzling to many consumers including women at risk for breast cancer. Numerous studies label the isoflavone genistein in soy as a natural compound that can prevent breast cancer. At the same time, increasing numbers of reports suggest that genistein may be a risk factor for developing breast cancer.

Although this seems contradictory, it makes perfect sense to Xiaohe Yang, PhD, associate professor with the North Carolina Central University Nutrition Research Program at the North Carolina Research Campus in Kannapolis. Yang researches dietary and hormonal modulation in relationship to breast cancer risk and prevention. He specifically focuses on erbB-2/Her2 breast cancer, which is a group of more aggressive breast cancer caused by the overexpression of the Her2 tumor protein. Her2 occurs in about one-third of all human breast cancers.


Soy/Genistein Findings
Funded by a grant from the American Cancer Society, Yang is researching the differentiation of soy/genistein-induced responses based on exposure to genistein at a specific time and age and breast cancer subtype. Yang has found in a mouse model that genistein, which is a phytoestrogen or natural estrogen found in plants, can act as a preventative agent against the development of breast cancer, especially when the exposure comes at puberty or earlier in life. Current literature on soy consumption and breast cancer prevention supports this finding.

For adults, Yang’s findings suggest that exposure to soy/genistein may be a risk factor for certain subtype of breast cancers. Using an erbB-2 transgenic mouse model his research found a link to increased activities in both estrogen receptors (ER) and the erbB-2/Her-2 cellular signaling network in pre-cancerous mammary tissue exposed to soy. In other words, the mutual interaction or “cross talk” between ER and Her2 can work together to accelerate cell division and the growth of cancerous tumors. This suggests that adult exposure to soy/genistein may stimulate ER-erbB-2 interaction and tumor growth.

In another cell line-based study, which was published in the journal Carcinogensis, Yang found that genistein induces the strongest growth promotion effect on cancer cells that are positive for both ER and erbB-2/Her2, as compared to other subtypes.  Although erbB-2/Her-2 overproducing breast cancers tend to be ER negative, there are still a substantial portion of breast cancers that are double positive. Yang’s studies suggest breast cancer survivors or patients with erbB-2/Her2 and ER double positive tumors should be aware of the possibility that they could be “more vulnerable to the potential stimulation from genistein due to ER and Her2 signaling.”

“Genistein-induced interaction between these two master regulators activates a lot of cellular activities that stimulate the double positive tumors” he commented. “However, this does not change the healthy and beneficial effects of regular intake of soy food in a healthy population, especially for youngsters. The finding of soy/genistein associated risk for the double positive tumors makes more sense for women with a high risk of breast cancer to avoid an unnecessary risk by limiting consumption of soy products and supplements.”

Breast Cancer Resources:American Cancer

Cancer Compass

Cancer is a Preventable Disease

Centers for Disease Control

Dr. Susan Love Research Foundation

A Life’s Work
Yang’s interest in hormonal modulation of breast cancer risk started during the early days of his career. He was mentored by Ann Thor, MD, one of the leading breast cancer researchers in the country.  In Thor’s lab, Yang used a transgenic mouse model engineered with over-production of erbB-2/Her-2, to study the effect of dietary and environmental factors on erbB-2/her induced tumors. He uses a similar model in his laboratory today.

Working with Thor, he was part of the group that published the findings that a soy-rich diet provides better protection from mammary tumor development in erbB-2/Her-2 transgenic mice exposed to high levels of estrogen. They also found that a low-dose of soy exposure can interfere with the ability of Tamoxifen, a common drug used for breast cancer prevention, to prevent tumor development.

Yang’s lab is also studying other natural compounds like resveratrol, a phytonutrient found in grapes and several types of berries, to optimize its preventative or therapeutic benefits in relation to breast cancer. His overall goal is to develop new models for preventative and therapeutic approaches that target Her2 breast cancers along with the mechanistic understanding of potential risk factors that may modify erbB-2/Her-2-mediated tumor development.

Since the majority of breast cancers are caused by environmental factors, Yang and his research team are centering their next research projects on epigenetics and stem cell reprogramming to unravel the gene-environmental interactions in breast cancer development. Their research is advancing the ability of scientists to understand how and when the environment triggers the onset of diseases like Her2 breast cancer and to develop more effective preventative regimens and therapeutic treatments.

For more information, visit NC Central University Nutrition Research Program.

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