Cancer of the breast is currently one of the major causes of morbidity and mortality in females all over the world. Compared to Western countries such as the US and Europe, the incidence of breast cancer in Asia is relatively less (about 1/3). However, this pattern is rapidly changing – in countries like Singapore, the incidence of breast cancer has skyrocketed over the past 20 years. This rapid increase in breast cancer is thought to arise from a number of factors, for example females having fewer children, an earlier age of puberty, and a later onset of menopause. Over the past few decades, considerable research efforts have been invested in identifying and improving ways to diagnose, treat, and prevent breast cancer. Some of this research is being performed locally.

One central area of local research lies in developing faster, cheaper, and more accurate technologies for breast cancer screening, aimed at detecting breast cancers at an early stage where the disease can be effectively treated by surgery.

At present, the gold standard for screening is mammography. Although an effective and proven technology, mammography also has a number of challenges including patient discomfort and a requirement for skilled radiological interpretation. To address this problem, scientists such as Yoshiaki Ito and Saraswati Sukumar of the Oncology Research Institute (ORI) at the National University of Singapore and the Institute of Molecular and Cell Biology (IMCB) have been working to develop a blood test for breast cancer, which exploits the fact that the DNA in cancer cells often display a characteristic chemical alteration called methylation. By looking at the DNA methylation fingerprint of a patient’s blood sample, it may be possible one day to diagnose breast cancer at home using a single pin-prick of blood, with a test kit purchased from the local pharmacy.

Compared to other cancers, one fortunate aspect of breast cancer is that there are a number of treatment options available for patients with advanced stage disease. However, not all breast cancers will respond to the same treatment, and clinicians are often faced with the dilemma of having to choose which treatment to use, especially since some of these treatments are associated with potentially serious side effects and are quite expensive. Another active area of local research lies in the area of personalized medicine, where scientists are developing methods to identify, prior to treatment, those breast cancers that would be most responsive to a particular treatment regimen. The use of gene expression profiling (GEP) has proved to be very useful in this regard. In GEP, cancer samples from patients are placed upon a ‘genechip’ or ‘DNA microarray’, which allows one to catalog the repertoire of genes that are selectively activated or repressed. This pattern of activation and repression forms a so-called ‘molecular portrait’ of the cancer, and by comparing this portrait to a database of previously treated cancers, one can then predict the likelihood that a cancer will respond to a particular treatment or not. As one example, our group at the National Cancer Centre (NCC) has recently identified a ‘portrait’ that predicts if a breast cancer will respond to tamoxifen, a commonly used breast cancer drug.

Scientists all over the world are performing also genetic susceptibility studies to identify the specific genes that confer increased breast cancer risk. In Singapore, Kanaga Sabapathy’s lab at the National Cancer Centre (S) has recently shown that a genetic variant of a well-known cancer gene, p53, may contribute towards an individual developing breast cancer. Similarly, Liu Jianjun at the Genome Institute of Singapore is investigating whether components of the estrogen receptor pathway, a cellular pathway important in certain types of breast cancer, may be different in individuals with and without breast cancer.

In conclusion, this is currently a very exciting time for breast cancer research. In addition to the few examples mentioned here, significant work is also taking place in Singapore in other related areas, including the development of novel therapeutics, and the genetic identification of individuals most likely to experience drug-related side effects. Integrating the information from all these studies will undoubtedly lead to the creation of important new clinical applications to treat and manage patients with breast cancer.

Figure 1 : A DNA Microarray. Each spot represents one gene. A red spot indicates that genes is activated, while a green spot indicates repression. Yellow indicates that the gene is moderately active.

Patrick Tan, MD PhD
Principal Investigator
National Cancer Centre/Genome Institute of Singapore