Soy’s most active isoflavone, genistein, has been identified as boosting the efficacy of tamoxifen - a medication used to treat and prevent breast cancer.
But the Georgetown University researchers also demonstrated why eating or drinking soy-based foods while being treated with tamoxifen reduced its effectiveness and promote relapse.
Dr Leena Hilakivi-Clarke, senior study investigator and professor of oncology at Georgetown University, also highlighted the inconsistency of genistein and how it behaves differently in distinct ethnic populations.
"Genistein, which has a similar structure as oestrogen activates both human oestrogen receptors to a degree,” she said.
“Oestrogen drives most breast cancer growth, yet high soy intake among women in Asian countries has been linked to a breast cancer rate that is five times lower than Western women, who eat much less soy," she added.
"So why is soy, which mimics oestrogen, protective in Asian women?"
Ethnic efficacy
However, scientists are stumped as to whether the protective effect reflects soy consumption during a lifetime or if a similar result can be achieved by starting soy intake for the first time during hormone treatment.
The study, published in Clinical Cancer Research, fed a diet supplemented with either 500 parts per million (ppm) genistein for the rat’s lifetime (lifetime geneistein group) or 0ppm as a control.
Mammary tumours were induced in the rats after which a group of control diet–fed rats were switched to the genistein diet (adult genistein group).
When the first tumour in a rat reached 1.4 centimetres (cm) in diameter, tamoxifen was added to the diet and a subset of the previously control diet–fed rats were also started on genistein (post-diagnosis genistein group).
The team found that the lifetime genistein group had a reduced tamixifen resistance from the start of the supplementation, compared with the post-diagnosis genistein groups.
The risk of recurrence was found to be lower both in the lifetime and in the adult genistein groups than in the post-diagnosis genistein group.
Autophagy action
Study lead researcher, Dr Xiyuan Zhang attributed genistein’s ability to inhibit a mechanism called autophagy that allows cancer cells to survive. This could explain why it also helps tamoxifen work.
However, it was a different outcome in the rats when soy consumption commenced after breast cancer developed.
“Consuming genistein after breast cancer develops in the animals did not trigger an anti-tumour immune response to eliminate cancer cells,” said Zhang.
“We do not know yet why this made the animals resistant to the beneficial effects of tamoxifen and increased risk of cancer recurrence," she added.
"While many oncologists advise their patients not to take isoflavone supplements or consume soy foods, our findings suggest a more nuanced message - if these results hold true for women,” said Dr Hilakivi-Clarke.
“Our results suggest that breast cancer patients should continue consuming soy foods after diagnosis, but not to start them if they have not consumed genistein previously."
In response to an appeal from the German authority back in 2015, the European Food Safety Authority (EFSA) said that soy isoflavones in food supplements did not pose a health risk to post-menopausal women.
Source: Clinical Cancer Research
Published online ahead of print: doi: 10.1158/1078-0432.CCR-16-1735
“Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats.”
Authors: Xiyuan Zhang, Katherine Cook, Anni Warri, Idalia Cruz, Mariana Rosim, Jeffrey Riskin, William Helferich, Daniel Doerge, Robert Clarke and Leena Hilakivi-Clarke.