Background: The effect of cruciferous vegetable intake on breast cancer survival is controversial at
present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates
are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived
enzyme myrosinase. The main Isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl
ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their anti-breast cancer
Objective: The aim of this article is to systematically review the evidence from all types of studies, which examined
the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer.
Methods: A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to
27 April 2020. Peer-reviewed studies of all types (in vitro studies, animal studies, and human studies) were selected.
Results: The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies.
The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial
and varied greatly across human studies. Most of these trials were observational studies conducted in
specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained,
which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer.
Evidence from in vitro studies showed that sulforaphane and other ITCs reduced cancer cell viability and proliferation
via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial
mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying
enzymes. These are the essential pathways that promote the growth and metastasis of breast cancer. Noticeably,
benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of
chemo-resistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at
variable range of concentrations and benzyl isothiocyanate appeared to have a relatively lower inhibitory concentration
IC50. The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have
also been highlighted in this article.
Conclusion: Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential
therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer
drugs, with sulforaphane displaying the greatest potential.