Ten Facts about Triple Negative Breast Cancer (TNBC)

In Singapore, breast cancer is the most commonly diagnosed cancer for more than 40 years and it is the leading cause of death in cancers affecting women. There are more than 7000 new cases a year (from 2006-2010) and it has been a rising incidence trend. The incidence rises sharply after 30 years old to peak in the 60s. Of the ethnic groups in Singapore, the age-standardised incidence rate is higher for Chinese than for the other ethnic groups.

When a person refers to a Singaporean, he could mean a Singaporean of various different ethnicities, characterised by different language, culture, dietary habits or dressing. Whether it is a Chinese, Malay, Indian or other Singaporean, these characteristics can be fairly unique. Likewise, in breast cancer, we are beginning to realise that there are several subtypes of breast cancer. Broadly, there are the hormone positive breast cancer, Her2 positive breast cancer and the triple negative breast cancer. They have certain unique characteristics and behaviour. These tumour subtypes were classified initially by gene tests known as expression profiling.

Triple negative (or triple-negative) breast cancer is increasingly being studied and some information may change as more is known about this type of breast cancer. Triple negative breast cancers do not express oestrogen (or estrogen) receptors (ER), progesterone receptors (PR) or Her2 receptors. This would also mean that such breast cancers do not respond to hormone or endocrine therapy or to Her2 directed therapy.

Some features of triple negative breast cancer (TNBC) are:

1. They seem to occur in higher frequency in younger women and may be associated with a higher likelihood of BRCA1 gene expression.

2. Women of African or Hispanic ancestry seems to have a higher rate of triple negative breast cancer. TNBC in Asian breast cancer patients have not been as well studied. However, our own group and others have shown many of these are young breast cancer patients and many may be related to BRCA1 hereditary breast cancer.

3. The reliability of markers to identify triple negative breast cancer is an area of research. There seems to be several histologic tumour types within TNBC.  The selection of such tumours based on ER, PR and Her2 negativity does not mean that they are uniform. In addition, assay techniques for hormone receptors and Her2 are important. An unreliable laboratory will end up having more triple negative breast cancers! Basal-like breast cancer is also triple negative but have other specific indicators like CK 5/6, and EGFR status. Many current treatment studies for triple negative breast cancers tend to explore treatment for the whole TNBC group.

4. Early stage triple negative breast cancer can be treated effectively with surgery and many patients may have breast conserving surgery. This is often followed by radiation and adjuvant chemotherapy.

5. Adjuvant chemotherapy (chemotherapy given after surgery) for triple negative breast cancer can be highly effective at preventing a recurrence. At OncoCare Cancer Centre, this is what we would often discuss with patients who present with early triple negative breast cancer. This is an important modality as there is no option of using endocrine (hormonal) therapy or Her2-directed therapy such as Herceptin.

6. Triple negative breast cancer recurs more commonly than other types of breast cancer such as the hormone-positive or endocrine-responsive breast cancer. It accounts for a disproportionate percentage of breast cancer deaths. Studies suggest that recurrences tend to occur within the first 5 years after diagnosis for TNBC.

7. The ability to spread and metastasise is similar to other breast cancer subtypes but they have a shorter time to relapse and death. They have been described as aggressive breast cancer because of this. There seems to be a higher likelihood for brain metastasis or spread to the brain for TNBC.

8. Current chemotherapy treatment strategies for triple negative disease include anthracyclines (such as adriamycin, epirubicin), taxanes (such as paclitaxel, docetaxel) , ixabepilone, platinum agents (cisplatin and carboplatin) and eribulin (Halavan). Triple negative breast cancers tend to respond well to chemotherapy but some of the responses seem to be shorter than for the other subtypes.

9. Treatment studies of EGFR (epidermal growth factor receptor) inhibition has been proposed with mixed results. Interesting newer agents such as those targeting the poly(ADP-ribose) polymerase (PARP) inhibitors have been evaluated and seems to work better for the subgroup related to BRCA1or BRCA2 mutation carriers.

10. Genetic counselling should be considered in triple negative breast cancer patients particularly younger TNBC patients as some are related to hereditary breast cancer.

“Expert knowledge means better care for cancer”

Written by:

Dr Peter Ang
MBBS (Singapore)
MMed (Int Med)
MRCP (UK)
FAMS (Medical Oncology)