Do Phytoestrogens Increase Risk of ER Cancers (Breast, Ovarian Etc)?

Check out this answer from Consensus:

The relationship between phytoestrogens and the risk of ER cancers is complex and influenced by various factors, including the type of phytoestrogen, the timing and amount of intake, and the ER status of the tumor. While there is evidence suggesting that phytoestrogens may reduce the risk of ER-negative breast cancers, their effects on ER-positive cancers are less clear and may even be stimulatory at low doses. More research is needed to fully understand the implications of phytoestrogen intake on cancer risk and to establish clear dietary recommendations.

Phytoestrogens are plant-derived compounds that can mimic or modulate the action of estrogen in the body. There has been significant interest in understanding whether phytoestrogens influence the risk of estrogen receptor (ER) cancers, such as breast and ovarian cancers. This synthesis aims to summarize the current research findings on the relationship between phytoestrogen intake and the risk of ER cancers.

Key Insights

• General Protective Effects:
  • Several studies suggest that phytoestrogens may have a protective effect against breast cancer, particularly in populations with high dietary intake of these compounds1 5 9 10.
  • Epidemiological data indicate a potential protective role of phytoestrogens against breast cancer, especially when consumed during adolescence or at high doses6 9.
• ER-Positive vs. ER-Negative Tumors:
  • Phytoestrogens like genistein and daidzein can stimulate the growth of ER-positive breast cancer cells at low levels, but may inhibit ER-negative tumor growth5 7.
  • Intake of coumestrol is associated with a decreased risk of ER-negative and PR-negative breast tumors, but not ER-positive tumors1.
  • Low intake of certain phytoestrogens (genistein, daidzein) is associated with a higher risk of ER-negative tumors compared to ER-positive tumors7.
• Mechanisms of Action:
  • Phytoestrogens can bind to estrogen receptors (ERα and ERβ) and exhibit both estrogenic and antiestrogenic activities, depending on the context and concentration2 3 4 8.
  • These compounds can modulate multiple molecular targets in breast cancer cells, including cell cycle regulators and tumor suppressor genes, and may exert antiangiogenic and antimetastatic effects8.
• Controversial and Inconclusive Findings:
  • Some studies report that phytoestrogens can stimulate the proliferation of estrogen-sensitive tumor cells at low doses, raising concerns about their safety in certain contexts4 5.
  • The evidence is mixed regarding the protective effects of phytoestrogens on breast cancer risk, with some studies showing no significant reduction in risk9.

Do phytoestrogens increase risk of ER cancers (breast, ovarian etc)?

Leena Hilakivi-Clarke has answered Unlikely

An expert from Georgetown University in Breast Cancer

Observational epidemiological studies show that women consuming soy foods, especially if they already consumed during childhood, have significantly lower risk of developing breast cancer than women who do not consume soy foods. Findings obtained in preclinical (animal) studies are supportive of human data, and indicate that phytoestrogens in soy foods (genistein) reduces mammary cancer risk. Controversy regarding soy food intake and breast cancer risk originates from findings in human breast cancer cell lines. The most commonly used estrogen receptor positive (ER+) cell line – MCF-7 cells – starts growing if they are exposed to genistein. Another ER+ breast cancer cell line – T47D – is inhibited by genistein. A possible explanation for these opposing findings is that T47D cells express higher levels of ERbeta receptor. Genistein preferentially binds and activates ERbeta, and ERbeta opposes cancer cell proliferative actions of ERalpha. However, genistein also binds and activates ERalpha. Human breast is reported to express higher levels of ERbeta than ERalpha, although recent findings question if the antibodies used to detect ERbeta in human breast are specific for this ERbeta protein, or in fact detect some other protein altogether.

I personally consume some (1-2 times per week) soy foods, for the following two reasons: (1) soy foods may affect my gut microbiota in a way that protects me against many diseases by boosting my immune system and modulating my epigenome, and (2) soy is a great protein source. It may also protect me against breast cancer, and I do not believe it puts me into increased risk. I am a 61-year old woman who is lucky enough not to have been diagnosed with breast cancer.

Do phytoestrogens increase risk of ER cancers (breast, ovarian etc)?

José J Gaforio has answered Unlikely

An expert from University of Jaén in Immunology

The incidence rates of certain chronic diseases, such as certain cancers and cardiovascular disease, are higher in Western countries, where people consume a diet rich in fat and animal protein, compared to countries that follow a Mediterranean diet rich in plant foods that contain phytoestrogens. Therefore, it has been postulated that phytoestrogens may be involved in conveying the beneficial effects attributed to the Mediterranean diet. In fact, phytoestrogens are abundant in the plasma and urine of subjects living in areas with a low cancer incidence rate.

The two main groups of phytoestrogens are isoflavonoids and lignans. It is widely assumed that the intake of lignin-rich foods is part of a healthy diet, and several reviews have conveyed information about lignans derived from different sources in the plant kingdom.

For example, the natural lignans found in olives and Virgin Olive Oils, which is the main source of fat in the Mediterranean diet, are (+)-pinoresinol and 1-acetoxypinoresinol. It has been reported that pinoresinol and 1-acetoxypinoresinol have several health benefits, from free radical scavenging activity to biological effects in vitro and in vivo. They have been associated with antitumor activity, especially in breast tumours, and with a decrease in the expression of proteins and molecules, such FASN and HER2 tyrosine kinase, that are directly implicated in cancer processes. Both compounds also possess chemical antioxidant activity.

References also suggest that (+)-pinoresinol exerts anti-inflammatory activity, specifically through the inhibition of NO but also through the inhibition of inflammatory mediators such as PGE2, COX-2, TNFα, IL1β, IL-6 and NF-κβ. Therefore, consumption of this compound could be clinically applied to target inflammatory processes, which are the basis for the initiation of several diseases such as cancer.

Do phytoestrogens increase risk of ER cancers (breast, ovarian etc)?

Shu-Lin Liu has answered Extremely Unlikely

An expert from Harbin Medical University in Microbiology

Phytoestrogens have both estrogenic and anti-estrogenic activities; when the physiological estrogen is too high, phytoestrogens may compete with it for the receptor, thus lowering the risks of breast and ovarian cancers.

Do phytoestrogens increase risk of ER cancers (breast, ovarian etc)?

Vilma A Sardão has answered Unlikely

An expert from University of Coimbra in Cell Biology, Biochemistry, Food Science

According with current literature, there are no clear evidences showing a direct effect between phytoestrogens consumption and breast or ovarian cancer development. In fact, several epidemological studies showed a decreased risk of breast cancer and lower incidences of menopausal symptoms and osteoporosis in women from countries with high phytoestrogens consumption, raising the interest on these compounds as an alternative to hormone replacement therapies. Phytoestrogens are a group of plant-derived substances that have the ability to bind to the estrogen receptors and exert estrogenic or antiestrogenic activities. They can bind to both Estrogen Receptor alpha or Estrogen Receptor beta, although with a higher affinity for Estrogen Receptor beta. Interesting, the activation of estrogen receptor beta down-regulates the action of estrogen receptor alpha activation, decreasing cell proliferation in certain organs such uterus. Further, estrogen receptor beta is also a potent tumor suppressor and has crucial roles in many cancer types. Acting through estrogen receptor beta could explain why phytoestrogens appear to decrease the risk or certain cancers. Several phytoestrogens have also an in vitro antioxidant properties through hydrogen/electron donation via hydroxyl groups ,thus acting as free radical scavengers and inhibiting in vivo the development of coronary heart disease and some types of cancer. Beyond those direct effects phytoestrogens are also able to up-regulate Manganese-Superoxide dismutase(MnSOD) and catalase (two important antioxidant enzymes) in some cellular models, contributing to the observed antioxidant effect. Thus, in my opinion, under normal conditions, increased risk of breast or ovarian cancer does not result from a phytoestrogen-rich diet. However, if an estrogen-dependent tumor is already formed, precautions should be taken if you thinking to change your eating habits or phytoestrogens supplements.

Do phytoestrogens increase risk of ER cancers (breast, ovarian etc)?

Brenda  Alston-Mills has answered Likely

An expert from Michigan State University in Breast Cancer, Cell Biology

It is during development of the mammary gland that phytoestrogens have a very positive influence. They affect maturation of the gland as the female reaches puberty such that division of the epithelial cells will differentiate to the extent that those cells are less likely to divide and therefore holding off transformation.

On the other hand, if there are cancer cells that have been initiated then phytoestrogens can stimulate transformation the same way that estrogens can. This, intake in adulthood after the gland has developed, may be detrimental and may promote epithelial cell transformation and subsequent tumor development. There is literature to support this. Work that we performed on mice also support this claim. I cannot address any other female organ and phytoestrogens.