Link Between Soy Consumption and Breast Cancer Remains Complicated Interview with:
Xiyuan Zhang PhD
and Leena Hilakivi-Clarke, PhD
Professor of Oncology
Georgetown University
Research Building, Room E407
Washington, DC 20057 What is the background for this study? What are the main findings?

Response: Breast cancer is the most common cancer type in women and it also is the second leading cause of death by cancer in the United States. Every year, over 200,000 new cases of breast cancer are diagnosed in the US and this number reached over 1.5 million worldwide in 2012.

Asian women exhibit much lower risk of breast cancer than Caucasian women, accounting for about one fifth of the breast cancer incidence in Western women. Therefore, researchers have been intensively studying and aiming to decipher the difference between these two populations. Results of previous research from our laboratory and by others, in animal models and humans, indicate that higher intake of soy foods or soy isoflavone genistein during childhood is associated with reduced breast cancer risk. However, findings done using human breast cancer cells indicate that soy isoflavones stimulate growth of breast cancer cells. Thus, there is an apparent controversy regarding soy isoflavones and breast cancer.

70% of all breast cancer cases are estrogen receptor positive (ER+) and are therefore treated with endocrine therapy, including with tamoxifen. Although these treatments effectively prevent recurrence in half of the ER+ breast cancer patients, the other half are resistant or develop resistance to the endocrine therapy and recur. Intriguingly, several studies done using human breast cancer cells in culture or in mice found that soy isoflavone genistein negates tamoxifen’s effects. However, observational studies in women suggest that those patients who consume most soy foods have the lowest risk of breast cancer recurrence. The present study was designed to address these conflicting findings using a preclinical animal model and to determine if lifetime isoflavone intake has different effect on tamoxifen’s ability to treat breast cancer than intake that starts when cancer is detected. What are the main findings?

Response: Results of our study show that lifelong genistein consumption significantly improved the effects of tamoxifen treatment: it lowered the risk of tamoxifen resistance and risk of recurrence. These beneficial effects were linked to improvement in anti-cancer immune responses. In contrast, animals that started their genistein consumption after the breast cancer diagnosis exhibited least responses to tamoxifen and the highest risk of recurrence. No changes in tumor immune responses were seen in this group. What should readers take away from your report?

Response: Due to the significantly lower risk of breast cancer among Asian women who consume significantly more soy foods than Western women, and the public interest in soy consumption as a means to promote health, we conducted a preclinical study trying to address the prior controversies related to soy and breast cancer. These controversies relate to the apparent estrogenicity of isoflavone genistein, questioning the safety of soy foods to be consumed by patients with ER+ breast cancer who are treated with endocrine therapy.

Our results that lifelong genistein intake improved response to tamoxifen treatment and prevented recurrence are in line with human observational studies. Together these findings indicate that women who have consumed soy foods before being diagnosed with breast cancer can continue consuming them also during endocrine therapy. Continued consumption may even be beneficial and prevent recurrence of breast cancer. However, our animal study also suggests that it may not be safe to start consuming soy foods during endocrine therapy, if a patient has not previously consumed them. What recommendations do you have for future research as a result of this study?

Response: Our research made the connections between improved response to tamoxifen therapy and alterations in anti-tumor immune responses by lifetime genistein consumption. Future research are needed to causally link the changes in immune responses to prevention of endocrine resistance and breast cancer recurrence. Is there anything else you would like to add?

Response: This preclinical study was conducted in animals. Although the model we used is shown to closely mimic breast cancer in women, translation of our results to possibly influence clinical decisions among patients should be done with caution.

The study was conducted by funding received from the National Cancer Institute and American Institute for Cancer Research, as well as from a generous private donation from the Solomon family. None of the funding sources have any direct links to soy food industry. Further, none of the authors have any conflicts of interests that would have affected any aspects of the study. Thank you for your contribution to the community.

Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats
Xiyuan Zhang, Katherine L. Cook, Anni Warri, Idalia M. Cruz, Mariana Rosim, Jeffrey Riskin, William Helferich, Daniel Doerge, Robert Clarke and Leena Hilakivi-Clarke
DOI: 10.1158/1078-0432.CCR-16-1735 Published 1 February 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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