CancerWomen’s Health

Genistein may be useful for the treatment of triple-negative breast cancer

By January 12, 2022 No Comments
Genistein may be useful for the treatment of triple negative breast cancer

Modern research interest in soyfoods began with a focus on cancer prevention and treatment.1 Much of this interest can be attributed to the soybean being a uniquely rich source of isoflavones, and in particular, genistein. New pre-clinical research by Sharma et al.2 suggests that genistein may have a role in the prevention and treatment of one of the most aggressive, most difficult to treat forms of breast cancer — triple-negative breast cancer (TNBC). Due to its molecular etiology, these tumors do not respond to endocrine therapy or molecular target-directed therapies. Therefore, there is an urgent need for optimal therapeutic regimens.

TNBC is characterized by a subtype of invasive breast cancer that does not express three important molecular markers including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2.3 TNBC occurs in about 10–15% of all diagnosed breast cancers and more likely affects premenopausal young women under 40 years old, African Americans, Hispanics, and/or those with a BRCA1 gene mutation.4,5 TNBC is highly aggressive as compared to the hormone receptor-positive and human epidermal growth factor receptor enriched breast cancer.6

The new research in question consisted of two preclinical patient-derived xenograft (PDX) orthotopic mouse models. That is, NSG mice were surgically implanted into the mammary pads with one of 2 triple-negative tumors (BCM -3204 or TM00091) derived from a Caucasian female. NSG mice are characterized by a lack of B cells, T cells, and functional natural killer cells. This severe immunodeficiency makes these mice ideal PDX recipients for engraftment with malignant TNBC tissue.

Following implantation, the mice were fed either the control diet, which was isoflavone-free and contained corn oil rather than soybean oil, or the control diet to which had been added genistein at a concentration of 250mg/kg. For comparison, humans typically consume about 500g (dry weight) of food daily. If genistein intake was 50mg/d, which is certainly the case for some women in places like Shanghai, China, the genistein concentration of the diet would be 100g/kg.7

At study termination, in comparison to the control mice, tumor weight was significantly decreased (p<0.01) in mice consuming the genistein-containing diet and implanted with TM00091 tumors. In mice implanted with BCM-3204 tumors, tumor weight was also decreased in response to genistein, but the results were not quite statistically significant (p=0.0559). In addition, genistein treatment was effective in reducing tumor volume, especially at 22 weeks and 23 weeks of age, in mice bearing BCM-3204­­­­ tumors as compared to the control diet. Genistein treatment also significantly decreased tumor volume at 11 weeks and 13 weeks in mice engrafted with TM00091 tumors.

Sharma et al.2 noted that their results show that genistein significantly inhibited TNBC development in both tested models as compared to the control group without showing any harmful effects. They found that genistein treatment led to several important differentially expressed genes that are likely involved in the cancer metabolic pathway. Interestingly, Sharma et al.2 cited previous research in humans suggesting that genistein may enhance the efficacy of conventional treatment of metastatic colorectal cancer.8

Finally, the authors concluded that the dietary genistein concentration used in their study is equivalent to humans consuming 3 cups of boiled soybeans per day. The citation for the “3 cups” figure is a paper that discusses dose translation from animal to human studies.9  The amount of isoflavones provided by 3 cups of boiled soybeans is only moderately higher than the amount ingested by high-soy-consumers in Shanghai. Furthermore, since only one dose of genistein was used in this research, it is reasonable to speculate that a lower dose may have produced a similar benefit.

References

  1. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991;83:541-6.
  2. Sharma M, Arora I, Chen M, Wu H, Crowley MR, Tollefsbol TO, Li Y. Therapeutic effects of dietary soybean genistein on triple-negative breast cancer via regulation of epigenetic mechanisms. Nutrients 2021;13.
  3. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013;31:3997-4013.
  4. Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P, Schwartz GF, Park PK, Rosenberg AL, Brill K, et al. Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Cancer 2007;110:876-84.
  5. Alluri P, Newman LA. Basal-like and triple-negative breast cancers: searching for positives among many negatives. Surg Oncol Clin N Am 2014;23:567-77.
  6. Waks AG, Winer EP. Breast Cancer Treatment: A Review. JAMA 2019;321:288-300.
  7. Yang G, Shu XO, Jin F, Zhang X, Li HL, Li Q, Gao YT, Zheng W. Longitudinal study of soy food intake and blood pressure among middle-aged and elderly Chinese women. Am J Clin Nutr 2005;81:1012-7.
  8. Pintova S, Dharmupari S, Moshier E, Zubizarreta N, Ang C, Holcombe RF. Genistein combined with FOLFOX or FOLFOX-Bevacizumab for the treatment of metastatic colorectal cancer: phase I/II pilot study. Cancer Chemother Pharmacol 2019;84:591-8.
  9. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008;22:659-61.

This blog is sponsored by SNI Global and the United Soybean Board.

Dr. Mark Messina

Author Dr. Mark Messina

PhD in Nutrition, Director of Nutrition Science and Research, Soy Nutrition Institute Global. Expert in soyfoods and isoflavones.

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