ome plant-derived chemicals known as phytochemicals may offer a new strategy for arresting the progress of premalignant breast cancer or breast cancer in its early stages. Dr Huynh Hung from the Singapore National Cancer Centre says his laboratory has identified promising phytochemicals that can block the oestrogen-induced growth of breast cancer cells. These phytochemicals act by altering oestrogen receptors and suppressing the expression of genes important for breast cancer cell proliferation and tumour formation.

Epidemiological data has suggested that long-term exposure to the female hormone oestrogen can increase a woman's risk of breast cancer. Researchers have determined the presence of oestrogen receptors in a high proportion of primary breast cancers in women and found that oestrogen supports tumour growth.

In a novel approach, Huynh combined phytochemicals with "hormonal manipulation," or the use of physiological signals to encourage terminal differentiation in mammary epithelial cells. Differentiation restricts the ability of a cell to grow abnormally and encourages it to change its nature and survive in other types of tissue.

Epidemiological studies have also shown that women who start menstruating early in life, delay their first pregnancy, or complete menopause later face a higher risk of breast cancer. Women who menstruate early are exposed earlier and perhaps longer to the effects of oestrogen, thus increasing their cancer risk. In addition, the lifetime risk of breast cancer is two to five times higher in women who have a first pregnancy after the age of 30 than in women whose first pregnancy occurs before the age of 20. It has been hypothesised that a first pregnancy at a young age may differentiate breast cells early in life, after which the woman would become less susceptible to carcinogens.

In a paper published in the International Journal of Oncology last year, Huynh showed that the combination of a pure anti-oestrogen and a hormonal regime using testosterone enanthate in animals brought about a reduction in breast epithelial cell growth (Figure 1). Mammary epithelial cells became differentiated, and more importantly, a significant reduction in tumour incidence occurred, as well as the number and size of tumours borne.

Huynh says that these observations may provide an insight useful in designing new strategies for treatment and prevention of breast cancer. He adds, "This is especially relevant in developed countries, where social and economic forces have combined to make women bear fewer children at a later age than their mothers and grandmothers. These life decisions will lead to higher rates of breast and ovarian cancer."

Although it is not practical to suggest early pregnancy as a prevention strategy, a more pragmatic approach, he points out, would be to put young women with a high risk of breast cancer on a hormone regime. By stimulating mammary differentiation with female hormones, the potential exists that they could reduce their risk.

Huynh is using the same strategy of phytochemicals and hormonal manipulation to treat and prevent prostate cancer in men, based on the principle that the phytochemicals would block the action of the androgen (male hormone) receptor much as they do the oestrogen receptor in women.

For more information contact Dr Huynh Hung at cmrhuy@nccs.com.sg.