Certain types of breast cancers are considered estrogen-dependent, meaning that estrogen (via the estrogen receptor subtype ERα) actually causes the tumor to develop and grow. Given the estrogen-like properties of red clover isoflavones, it is important to establish whether supplementation could impact the risk of these cancers. While ERα can stimulate tumor growth, in vitro research suggests that ERβ may actually have the opposite function of suppressing tumor growth.[1] Red clover isoflavones preferentially bind to ERβ receptors, which could be beneficial in terms of cancer risk, but they can still bind to ERα receptors, particularly when present at higher concentrations.[2]
In women considered to be at a high risk of breast cancer due to family history or breast density patterns, supplementation with red clover for 1 to 3 years did not cause any changes in a marker of breast cancer (breast tissue density),[3][4] although this marker is not considered to be a highly accurate predictor of cancer risk.[5] When looking at isoflavones from soy or red clover, a 2010 meta-analysis found that isoflavones had no effect on breast density in postmenopausal women but slightly increased breast density in premenopausal women, although there were too few cases of breast cancer in the sample to assess the impact of isoflavones on breast cancer rates.[6] Given the rare occurrence of breast cancer, trials with larger sample sizes would be required to more accurately define the relationship between red clover isoflavones and breast cancer risk.
References
- ^Song D, He H, Indukuri R, Huang Z, Stepanauskaite L, Sinha I, Haldosén LA, Zhao C, Williams CERα and ERβ Homodimers in the Same Cellular Context Regulate Distinct Transcriptomes and Functions.Front Endocrinol (Lausanne).(2022)
- ^Jiang Y, Gong P, Madak-Erdogan Z, Martin T, Jeyakumar M, Carlson K, Khan I, Smillie TJ, Chittiboyina AG, Rotte SC, Helferich WG, Katzenellenbogen JA, Katzenellenbogen BSMechanisms enforcing the estrogen receptor β selectivity of botanical estrogensFASEB J.(2013 Nov)
- ^Powles TJ, Howell A, Evans DG, McCloskey EV, Ashley S, Greenhalgh R, Affen J, Flook LA, Tidy ARed clover isoflavones are safe and well tolerated in women with a family history of breast cancerMenopause Int.(2008 Mar)
- ^Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, Runswick S, Day NE, Bingham SARed-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial ISRCTN42940165Breast Cancer Res.(2004)
- ^Fritz H, Seely D, Flower G, Skidmore B, Fernandes R, Vadeboncoeur S, Kennedy D, Cooley K, Wong R, Sagar S, Sabri E, Fergusson DSoy, red clover, and isoflavones and breast cancer: a systematic review.PLoS One.(2013)
- ^Hooper L, Madhavan G, Tice JA, Leinster SJ, Cassidy AEffects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trialsHum Reprod Update.(2010 Nov-Dec)