Testing Vegetable Compounds to Boost Breast Cancer Survival
Center for Cancer Training
The relatively minimal side effects of most dietary interventions for primary cancer prevention, as well as for prevention of cancer recurrence, make such approaches appealing to cancer researchers. Li Tang, Ph.D., an Assistant Professor of Oncology at Roswell Park Cancer Institute, has focused her career on studying the anti-cancer properties of isothiocyanates, a group of naturally occurring phytochemicals found in cruciferous vegetables such as broccoli, cauliflower, and cabbage.
As a post-doctoral researcher, Dr. Tang used both epidemiology and laboratory approaches to explore whether a diet high in cruciferous vegetables helps prevent the development of bladder cancer or its recurrence. She also sought to understand how isothiocyanates affect cancer cells on a molecular level.
In the epidemiology studies, Dr. Tang and her colleagues found a strong association between a diet high in raw cruciferous vegetables and both a reduced risk of bladder cancer and increased survival after bladder cancer treatment.
Studies from other laboratories suggested these effects may be due to the way the body processes isothiocyanates, Dr. Tang explained, noting that the active compounds from the vegetables accumulate in the urine, which is excreted from the bladder. In molecular studies*, she and her colleagues teased out some of the reasons that this accumulation could be beneficial to the bladder. They found that isothiocyanates, at the levels found in the bladder, both arrest the cell cycle in cancerous cells – stopping them from dividing – and induce apoptosis, which causes cells to die.
Dr. Tang became interested in whether the isothiocyanates could have preventive effects in other organs, where the doses would not be as high as in the bladder. In 2011, she received an NCI career development award** to extend her work to breast cancer, using both epidemiology and clinical studies.
“For bladder and breast cancer, we’re looking at two different scenarios” for how the isothiocyanates may induce their anti-cancer effects, said Dr. Tang. Isothiocyanates do not accumulate in breast tissue at levels that could stop cell growth or cause cell death, but research from Dr. Tang’s and other labs has shown that the isothiocyanates may change the expression of the estrogen receptor in breast cancer cells. For breast cancers that express the estrogen receptor – about two-thirds of all tumors in the breast – the receptor can help feed cancer cell growth. Therefore, blocking the estrogen receptor is a target of modern hormone therapy for breast cancer, including tamoxifen and the selective estrogen receptor down-regulator, fulvestrant.
With her award, Dr. Tang is planning a randomized, pre-surgical study with 50 female breast cancer patients to see if isothiocyanates given orally – in the form of broccoli sprout extract produced at the Johns Hopkins University – can reduce expression of the estrogen receptor and change the expression of several genes that indicate breast cancer characteristics (such as aggressiveness). Because the usual time period between a biopsy for diagnosis of breast cancer and surgery is about 2 to 3 weeks, Dr. Tang and her colleagues can use that period of time – and tissue samples taken during the biopsy and surgery – for their biomarker study of isothiocyanates’ effects without interfering with the standard treatment. They plan to start enrolling participants by the end of 2012.
“We want to look at these biomarker changes to see whether isothiocyanates may be used long term to modulate breast-cancer survival,” explained Dr. Tang. Additional epidemiological information will be gathered through collaboration with the Pathways Study, an ongoing, prospective study of breast cancer survivors within the Kaiser Permanente Northern California Health System. This collaboration will provide information on diet, survival, and genetic profiles of breast tumors from over 3,800 women.
If their preliminary work yields positive results, Dr. Tang hopes to initiate a long-term, randomized trial testing whether an interview-based intervention can boost intake of cruciferous vegetables in breast cancer survivors, and whether that increased vegetable consumption “would have a long-term effect on breast-cancer survival.”
* Tang, L., & Zhang, Y. (2004). Dietary isothiocyanates inhibit the growth of human bladder carcinoma cells. Journal of Nutrition, 134, 2004-10.
* Bhattacharya, A., Tang, L., Li, Y., Geng, F., Paonessa, J. D., Chen, S. C., Wong, M. K., & Zhang, Y. (2010). Inhibition of bladder cancer development by allyl isothiocyanate. Carcinogenesis, 31, 281-86.
** Grant number: 1K07CA148888-01A1