In this interview we discuss the link between soy consumption and breast cancer, and the impact of soy supplements on gene expression in early-stage disease.
Today we are discussing the link between soy consumption and breast cancer. We are speaking with Jacqueline F. Bromberg, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, who treats patients with breast cancer and does work on the role of various pathways, including inflammation pathways that promote breast tumor growth. Dr. Bromberg was part of a recently published study in the Journal of the National Cancer Institute, which examined the impact of soy supplements on gene expression in early-stage breast cancer.
-Interviewed by Anna Azvolinsky
Cancer Network:Dr. Bromberg, let’s start with what we know about soy consumption and how the phytoestrogens may affect breast tumorigenesis. What do we know from epidemiological studies?
Dr. Bromberg: To begin with, epidemiological studies examining populations of individuals who consume soy at higher amounts than other populations-for example, the Asian population-we know that there is a reduction in the incidence of breast cancer. Whether that reduction is due to soy consumption or many, many other variables is not known. Certainly, if you take an Asian individual and move them to a Western society where soy intake is reduced, the intake of other foods-a fattier diet and one with much more meat-leads to an increased incidence of mammary tumorigenesis. So, again, epidemiological studies are difficult to interpret because of the many variables involved. In order to say that an increase in breast cancer is associated with a lack of soy, for example, or that soy is protective, one cannot make those determinations based on epidemiological studies.
Phytoestrogens-it’s a large field in the sense of how much phytoestrogen is present. What is the role of estrogen in promoting or being neutral with regard to breast cancer, let alone phytoestrogens? One can look at the European studies in women who received hormone replacement therapy-that is, they received estrogen as compared with studies in the United States where women were given both estrogen and progesterone. To give estrogen alone as a replacement in postmenopausal women, the incidence of breast cancer was not increased. That leads us to believe that the role of estrogens and phytoestrogens is far from clear, in terms of preventing, promoting, or being neutral with regard to altering the incidence of breast cancer. It is clear, however, that the combination of estrogen and progesterone in an American population increases the incidence of breast cancer. This highlights the difficulties in making interpretations about phytoestrogens or estrogens alone in modulating the incidence or behavior of breast cancers. That said, the mainstay of treatment in individuals who have estrogen receptor–positive breast cancer is to block the estrogen receptor signaling with drugs such as tamoxifen or toremifene; to degrade the estrogen receptor by using drugs like fulvestrant in the metastatic setting; or to prevent the production of estrogens using aromatase inhibitors. This would suggest that blocking the estrogen pathway, getting rid of the estrogen receptor, once one has breast cancer, is an important arm in combating or eradicating breast cancer.
So, my take on epidemiological studies is that we cannot make interpretations based on these studies-there are too many factors involved in singling out soy as a food or supplement that has any influence on breast cancer.
Cancer Network:Can you talk about the design of the study that you and colleagues conducted and the questions that were addressed?
Dr. Bromberg: The question was, what effect does a moderate to high amount of soy have over a few weeks’ period of time on the behavior of a breast cancer? The design was to take women diagnosed with early-stage breast cancer, either stage I or stage II, the majority being ER-positive but also HER2-positive and triple-negative, and randomize them to receive either a placebo packet or a soy packet once they were diagnosed and scheduled for their surgery, either a lumpectomy or mastectomy. And in that window of time between when women were diagnosed based on a core biopsy and the time of their surgery, they were taking either a soy or placebo supplement. We examined whether there was any difference in the expression of genes in those women who took soy vs placebo. The study was started a number of years ago and the technology has advanced significantly, allowing us to ask another question, which is, if we look at the genes expressed in the tumor biopsy, as compared with the genes expressed after taking the soy or placebo, what kind of changes could we see? We were unable to do that analysis for all of the specimens; we could only do that for a small number of them.
Cancer Network:Can you talk about the results of the study?
Dr. Bromberg: Initially, when we looked at all-comers, the genes that were differentially expressed in the soy group vs the placebo group, we did not find any significant differences. There was nothing there. The conclusion at that point could have been that there is no effect of soy on gene expression in a relatively short period of time. Then we thought, maybe the women taking the soy were metabolizing it differently or maybe they weren’t taking it, or maybe it is not digested adequately. So, we measured several soy metabolites in the bloodstream of these women. One is called genistein and the other is called daidzein. We asked the question, in those patients who had high genistein or daidzein levels, do we see differential expression of genes in that group as compared with the placebo group? In that context, we were able to identify differential gene expression. We don’t know why some patients had high levels of soy metabolites and other patients did not. And if you look at those genes that were differentially expressed in the high soy metabolite population, those genes were associated with a more proliferative phenotype, meaning genes involved in proliferation.
The implications would be that a small amount of soy can influence gene expression in those patients who had high levels of the soy metabolite. Now, it is important to note that we looked at the morphological phenotype of those tumor specimens, to see if the tumors with the higher gene expression of the proliferation genes are actually proliferating more. Do we see increased expression of a marker for proliferation? The answer is no. The cells were not proliferating more. So, if there is no evidence of actual proliferation, just that the genes have changed, maybe that will have no effect. It could be that the patients needed to be on the soy for much longer before the gene expression profile translates to increase in actual growth. Breast cancers do not grow that rapidly, even if you spur them on to grow. It takes months and months.
Cancer Network:Based on what we know so far, what are rational recommendations on soy consumption and soy supplements for healthy women?
Dr. Bromberg: Don’t take soy supplements, and eat soy in moderation. Eat a varied diet, and don’t eat soy in large amounts every day.
Cancer Network:Thank you so much for joining us today, Dr. Bromberg.
Dr. Bromberg: You’re welcome, I hope I was helpful.