DIM and Breast Cancer

By Dr. Keith Block

Evidence-based medicine is an important precept throughout healthcare today. Evidence-based medicine relies on the best scientific evidence available at any particular time to help clinicians make decision in caring for patients, although it should never replace clinical judgment. In using evidence-based medicine, we look at randomized trials, laboratory results and systematic literature reviews to decide which medications and lab tests to use – or not to use.

A 2013 article that appeared in the Townsend Report – “Estrogen Metabolite Ratios: Time For Us To Let Go,” written by Jacob Schor – alerted us to a change in the status of evidence regarding one of the laboratory tests that we use. Along with many other practitioners, we have been using a test that measures two different metabolites, or breakdown products, of estrogen in the body to measure risk for breast cancer. Estrogen, specifically the molecule estradiol, is transformed in the body by different enzymes into other molecules. The particular molecules in question in the estrogen metabolite ratio test are 2-hydroxyestrone and 16α-hydroxyestrone. A series of studies dating back to the 1980’s had indicated that 2-hydroxyestrone had a relatively inhibiting effect on estrogen receptors, which modulate the effect of estrogen on breast cancer cells and other cells in the body. 16 α-hydroxyestrone, on the other hand, binds strongly to estrogen receptors on breast cancer cells, where it is thought to cause a long-lasting stimulation of the estrogen receptors. This might increase breast cancer risk or promote breast cancer growth. Because of the interest in predicting breast cancer risk, a lab test was developed that measured the ratio of “good” 2-hydroxyestrone to “bad” 16 α-hydroxyestrone. In this lab test, women with higher ratios of “good” estrogen to “bad” estrogen were thought to have less risk of breast cancer than women with low ratios (i.e., more “bad” estrogen). 

This test received further credibility and found clinical application when it was noted that the ratio could be improved by consumption of cruciferous vegetables. In particular, the compound diindolylmethane (DIM), which is a breakdown product of the cruciferous vegetable phytochemical indole-3-carbinol (I3C), was observed to be associated with a better estrogen metabolite ratio. Both I3C and DIM were then formulated as dietary supplements. With this combination of a clinical test and an easy-to-implement intervention, both clinical use and research in this area took off. Many publications, both lab-based and clinically-based, appeared.

When enough studies have appeared in a field, it’s possible to do a systematic literature review on them to assess the state of the research in an area. When the studies are similar enough, researchers can use the data from all the studies, combined together, to do a meta-analysis that gives a quantitative assessment of what all the studies are saying. A group of researchers from Hamburg, Germany, found a total of 9 studies in which estrogen ratios were tested in women at risk for breast cancer. Combining the results of all 9 studies, the researchers found that the estrogen metabolite ratio actually turned out not to be correlated with whether a woman had breast cancer. There was some indication that the ratio, when measured in urine, might effectively predict cancer risk for premenopausal women, but when taken in the context of the whole study, this was not statistically significant.  

Since 2011, no studies effectively contradicting this study have emerged. Thus, at this time, we feel it is necessary to stop using the estrogen metabolite ratio test in our patients. The next question is, should we stop suggesting I3C or DIM to prevent breast cancer, or after breast cancer has been diagnosed?  This question turns out to be a little more complicated. Of course, we will not be suggesting these supplements to improve the estrogen metabolite ratio. But, in some ways, I3C and DIM are even more interesting for cancer patients than they were several years ago. The interest in theses phytochemicals may even extend beyond breast cancer.

Much of the research on the crucifer chemicals has taken place at the Karmanos Institute at Wayne State University in Detroit. Karmanos researchers have found that DIM, the active form in the body, is a truly multi-targeted marvel. It inhibits some of the molecular pathways involved in pancreatic cancer – NF-kappaB, the well-known inflammatory pathway COX-2 and the epidermal growth factor receptor targeted by the drug Tarceva. In a pilot clinical trial with prostate cancer patients, one patient taking a DIM formula had a 50% drop in his PSA level, one had stable disease, while 10 more had a short-lived decline in the rate at which their PSAs increased. And there are several indications that DIM may suppress breast cancer cell growth. It inhibits the growth of at least 4 different lines of breast cancer cells, including some that lack estrogen receptors. It can decrease the activity of molecules that help plow through normal tissues so that metastases can settle. It sensitizes breast cancer cells to the effects of Taxotere though its inhibition of NF-kappaB, as shown in animal experiments. It also increased the effect of the drug Herceptin on breast cancer cells that bear the HER-2/neu mutation. Interestingly, none of these effects have anything to do with estrogen metabolites.

For more information on The Block Center for Integrative Cancer Treatment, call (847) 230-9107 or visit BlockMD.com.