Feature Articles » In the New... Triple Negative Breast Cancer

by Dr Peter Ang

In recent years, the term “triple negative breast cancer” (三阴性乳腺癌) has been used to describe breast cancer. This is not a new type of breast cancer that is recently discovered! Understanding what it is has helped cancer doctors understand and treat this cancer better.

Advanced breast cancer has a varied history for different patients. There have been many instances of patients doing well for many years. Is this because the patient has eaten the right food, has had excellent treatment or is it the character of the tumour itself? To some extent, it is a combination of factors. Nonetheless, we increasingly understand that the natural biology of the tumour is important.

About 100 years ago, there was recognition that some cancers respond to hormonal treatment when a doctor treated a lady with advanced cancer by removing her ovaries with resulting response in the cancer.

Nowadays, we term this group of cancers hormone sensitive breast cancer and the tumours would express oestrogen or progesterone receptors. In 1998, there was approval for the use of a drug Herceptin to treat Her-2 positive breast cancers which are driven by the growth factor receptor called Her-2.

In other words, some breast cancer cells would have receptors on the cell surface receiving hormone signals, some would receive growth signals via Her-2 and some would have neither. This last group is what we call “triple-negative” (oestrogen, progesterone and Her-2 negative). There is a term, “basal-like” (the tumour cells begin from the basal layer of the breast ducts) which are sometimes used interchangeably with “triple negative”. However, not all basal-like tumours are triple negative although most of them are.

Although it is not a “new” type of breast cancer, research in the last couple of years has helped us understand these tumours in a different way. For starters, they would not respond to drugs targeting the hormonal pathway such as tamoxifen, or to Herceptin. In the United States, African Americans seem to develop more of such tumours.

Research by our collaborative group in Singapore had shown more hormone positive breast cancers in Chinese compared to Malays or Indians but this was a smaller cohort of patients and the triple negative cohort is about the same across these ethnic groups in Singapore (The Breast 2005. Vol 14, (Supplement 1), S49: P120).

There was an interesting observation that BRCA1 mutation carriers were more likely to have basallike breast cancers (Foulkes et al. J Natl Cancer Inst. 2003 Oct 1;95(19):1482-5).

This led to the thinking that the development of such cancers is closely related to the BRCA1 gene. Drugs that target this particular pathway might have an important role in treating triple negative breast cancers. Recent clinical trials using cisplatin, and a new class of drugs called PARP inhibitors have shown great promise.