Cruciferous vegetables contain a variety of sulfur-containing compounds called glucosinolates that can be converted into various isothiocyanates with chemopreventive activities against breast cancer. High urinary isothiocyanate levels have been found to be related to lower breast cancer risk among both premenopausal and postmenopausal women. One prospective study reported that breast cancer patients taking tamoxifen who also had relatively high cruciferous vegetable consumption were less likely to experience a recurrence than tamoxifen users with low intake.

Sulforaphane is an isothiocyanate that has been shown to reduce inflammation, inhibit both estrogen receptor positive (ER+) and estrogen receptor negative (ER-) breast cancer cell proliferation, and induce breast cancer cell apoptosis (programmed cell death). Sulforaphane acts to prevent the reduction of ER expression in human breast cancer cells. Sulforaphane has also been shown to reduce the growth of breast cancer stem cells and impair their viability. In addition, sulforaphane has been found to suppress primary tumor growth in a mouse model of breast cancer, as well as reducing axillary lymph node metastasis in mice. Now a new study has reported that sulforaphane inhibits Herceptin (trastuzumab)-resistant HER2+ breast cancer and reduces triple negative breast cancer stem cell populations.

Food sources of sulforaphane

Unlike some plant-based chemopreventive compounds, meaningful amounts of sulforaphane can be obtained from food. However, raw vegetables are best. In addition, lightly cooked fresh broccoli has been shown to be superior to lightly cooked frozen broccoli. Furthermore, raw broccoli sprouts or broccoli are far better sources of sulforaphane than cooked broccoli or freeze-dried broccoli pills. This is primarily because isothiocyanates are obtained from glucosinolates when the enzyme myrosinase is released from damaged plant cells.

Myrosinase is physically separate from glucosinolates in intact plant cells. Chewing or chopping a cruciferous vegetable enables the myrosinase to catalyze the reaction that converts its glucosinolates into isothiocyanates. This is part of the plant defense mechanism which is triggered when, for example, an animal chews the plant. This mechanism is disabled when such vegetables are cooked, although human intestinal bacteria facilitate some formation and absorption of isothiocyanates. In addition, glucosinolates are water soluble and can be leached into cooking water.

The following are the best dietary sources of sulforaphane:

Broccoli sproutsóby far the best source
Brussels sprouts
Bok choy or Chinese cabbage

Sulforaphane is also found in meaningful amounts in the following foods:

Cabbage, red
Collard greens
Mustard greens
Turnip greens

We recommend against consuming sulforaphane or broccoli pills that have been enhanced to boost the proportion of chemopreventive chemicals such as sulforaphane. The anticancer properties of broccoli are likely to be the result of synergistic interaction of its various chemical components. In addition, isothiocyanates may damage the DNA of normal cells at doses obtainable through use of broccoli extracts, sulforaphane supplements, and other concentrated sources.

Latest research finds sulforaphane inhibits Herceptin-resistant HER2+

The study referenced at the beginning of this news story was designed to investigate how sulforaphane's efficacy varies according to breast cancer subtype and to examine sulforaphane's actions against breast cancer stem cells. The authors first showed that sulforaphane inhibited triple negative breast cancer growth. A low concentration of sulforaphane (1 uM) also preferentially eliminated breast cancer stem cells from triple negative breast cancer. (Breast cancer stem cells have the ability to divide indefinitely, thereby driving tumor development and metastasis. Regular cancer cells are the progeny of such stem cells. Limiting the proportion of breast cancer stem cells limits the number of cells that can form tumors.)

On the other hand, the authors found that sulforaphane did not inhibit HER2+ breast cancer growth, even at high doses (over 100 μM). The authors then induced resistance to Herceptin (with PTEN deletion and long term Herceptin treatment) and increased the proportion of HER2+ breast cancer stem cells (by activating a positive feedback loop of IL-6 (interleukin 6) and NF-kB (nuclear factor kappa B)). Sulforaphane was found to have greater than 20-fold higher activity in these Herceptin-resistant HER2+ cells. Sulforaphane (1 uM) disrupted NF-kB activity and inhibited endogenous IL-6 production by 50%. Using a mouse model of breast cancer, the authors then demonstrated that sulforaphane (at a dosage of 50 mg/kg) reduced tumor formation rate by 70% and inhibited tumor volume by more than 90%. The authors conclude that sulforaphane inhibits Herceptin-resistant HER2+ breast cancer and breast cancer stem cells by disrupting a NF-kB and IL6 positive feedback loop.

Please see our articles on diet and Herceptin, HER2+, and triple negative disease for more information.