In general it is easier to recommend nutritional and botanical interventions in primary, secondary and tertiary prevention than it is during therapy. This concern is based on very good reasons, mostly based on safety and possibility of interfering with mainstream therapy. While almost all oncologists would recommend lifestyle and screening based primary prevention, fewer would recommend all aspect of secondary integrative prevention and only those “in-the-know” recommend much in the way of tertiary prevention. The degree and scope of these recommendations vary, but they fall in a fairly broad range of oncologist acceptance. However, when anything is discussed as an integrative nutritional or botanical intervention concurrent with treatment most oncologists will balk beyond simple dietary changes. The truth is that most of this is a theoretical and somewhat emotional argument as there is no data to contradict integrative interventions, but it is also true that absolute proof of safety is lacking. It can quickly become a circular argument. The biggest areas of controversy are centered on the use of anti-oxidants and plant estrogens (phyto-estrogens) during chemo or radiation therapy. As far as anti-oxidants are concerned, most oncologists argue that if we are using pro-oxidant chemotherapy and radiation therapy then anti-oxidants might interfere by protecting cancer cells. The published research data does not support this claim but it does not unequivocally disprove it either. Those that are proponents of their use state that anti-oxidants will only or highly preferentially protect normal tissues, thereby lowering toxicity of chemo or radiation. In fact, synthetic anti-oxidants are sometimes used to reduce cardiac toxicity when Adriamycin is administered without proven reduction in efficacy. Similarly, synthetic anti-oxidants are selectively used to protect normal tissues during head and neck radiation. Another example is the use of an anti-oxidant compound called MESNA to prevent bladder damage when using Ifosfamide. It does not make complete sense that one of these would be recommended while an antioxidant supplement would be prohibited, but the debate continues. Generally, more oncologists would support selective use of anti-oxidants in situations of salvage chemotherapy where cure is no longer possible, in favor of quality of life factors. On the other extreme are oncologists who do not even want patients to consume a lot of dietary anti-oxidants at any point. In my opinion, until we have clear safety data, when initial curative intent treatment is being used, it is probably prudent to stay away from high dose supplement anti-oxidants. However, it is reaching too far to tell patients to avoid an anti-cancer anti-oxidant anti-inflammatory diet during treatment. So, all I can say is, talk with your oncologist and based on mutual risk/benefit discussion, make a decision. Next, what about phyto-estrogens or any estrogens for that matter? This depends somewhat on what the estrogen receptor status is, but not completely. If a tumor is estrogen receptor (ER) “negative” does not always mean there are zero estrogen receptors. It just means that there are relatively few, but this is not precise in most cases. So a ER negative tumor does not have enough receptors to effectively fight the cancer using estrogen blockers, but on the other hand even some receptors will latch on to estrogen and possibly slowly fuel the growth. So, it would seem reasonable to avoid all estrogen if possible. Keep in mind that estrogen can come from ovaries (unless blocked by drugs) or from fat cell conversion. In an ER tumor that blockade is what is done as “targeted” therapy. In an ER- tumor this is not done, but adding more estrogen externally is not prudent because it is possible that some lower level receptors actually exist. One way to reduce estrogen load naturally is weight loss, which reduces the amount of fat available for hormone conversion to estrogen. Exercise is a prudent lifestyle modification for all the reasons mentioned as well as general health benefit. What about phyto-estrogens in particular? Although the same logic would seem to apply, plant estrogens are very weak in binding to estrogen receptors. We also know from some, but not all, epidemiologic studies that maybe phytoestrogen isoflavones are protective against breast cancer. Breast cancer incidence in the United States has been 4–7 times that in Asia, and isoflavone consumption in the United States is <1% of that in Asia. Intake in the US is <1mg/day , compared to 20 to 80 mg/d in Asian countries. This may sound convincing but is the reason epidemiology does not prove cause and effect. High phytoestrogen isoflavone soy consumption in Asia is only one of many differences in lifestyle compared with the US, any one of which might be more important. You would have to drink gallons of soy milk (or take a high dose supplement) to achieve the 20-80mg/day intake seen in Asia, but read on as this may not be a good idea. To explain the possible beneficial effect of soy this is what happens at the molecular level of the estrogen receptor. Phytoestrogens can act as an “agonist”, activating the receptor, which is not good. But it can also act as a “antagonist” by binding to the receptor and making the receptor unavailable to bind to stronger estrogens, like the ones from ovarian or fat sources. How much of which action will happen in any individual is unknown, and it actually gets more complicated. There are two types of estrogen receptor, ER-α and ER-β. ER-β is the preferred binding site of phytoestrogens and may have anti-proliferative effects, opposing the proliferative effects when ER-α is bound by estrogen. The interaction gets pretty complex, and no one knows if taking more has a bigger effect and on what receptor. Based on laboratory studies, this is probably very different from tumor to tumor. This is why it is not prudent to get carried away with taking large amounts of phytoestrogens which can occur in “pharmacologically” packaged high dose 50mg/day supplements. Vendors of these supplement products assert that the phytoestrogens will exert a purely anti-cancer antagonist role, but this strategy of “more is better” is a dangerous guessing game. Using this high dose supplement strategy is akin to playing Russian roulette with your life.