Breast cancer is the most common cancer among women in Singapore, and the incidence of this disease has increased threefold over the past three decades. Between 2011 and 2015, a total of 9,634 women were diagnosed with breast cancer, which amounts to one in three incidents of cancer in females1.
Breast cancer subtypes
If a lump is detected, a biopsy is performed to determine if it is malignant (cancerous) or non-malignant. If it is found to be malignant, it will be further analysed, through tumour markers, to ascertain the prognostic (recurrence risk) and predictive (treatment benefit) outcomes.
Breast cancers may behave differently in different patients. This means that one patient’s prognosis (chances of recovery and survival) and treatment plan could differ greatly from another’s. Breast cancers are classified into three different subtypes based on the status of estrogen receptors (ER) and progesterone receptor (PR) and HER2 receptors in the tumour. They are namely hormone-sensitive breast cancer, HER2- positive breast cancer and triple negative breast cancer.
Knowing the characteristics of a tumour, like its size, histologic grade, and subtype – whether it is hormone receptor-positive or hormone receptor-negative, could help predict whether the cancer will grow aggressively or less so, as well as interpret its impact on relapse and survival. For example, ER-positive tumours tend to grow less aggressively and may respond favourably to hormonal therapies, while HER2-positive tumours tend to grow more quickly than other types of breast cancer and are responsive to therapies that target HER2 such as trastuzumab.
Conventional breast cancer management
Treatment of breast cancer usually combines surgery, radiotherapy and chemotherapy. Depending on the size and position of the cancer, surgery may involve the removal of part of the breast (lumpectomy) or the whole breast (mastectomy). In patients with large tumours or lymph nodes underneath the armpit, and those with tumour too large for lumpectomy, chemotherapy may be given first to shrink the tumour before going for surgery. In order to reduce the risk of cancer coming back, radiotherapy, chemotherapy, hormonal therapy and trastuzumab may be given to eliminate the remaining traces of cancer cells thereby reducing the risk of the cancer coming back. The cytotoxic drugs used in chemotherapy are designed to kill cancer cells, but they could also destroy healthy cells and bring about adverse side effects as well.
One of the challenges in the treatment of early breast cancer is to accurately predict which patient is at risk of future recurrence so that the treatment can be tailored accordingly. Besides the traditional ways of using the patients’ and tumour’s characteristics, studying the profiles of gene expression in the tumour can be a valuable tool in this regard. For example, the Recurrence Score from the 21-gene Oncotype DX test for invasive breast cancer has been found to identify a group of women who are at a very low risk of future recurrence with hormonal therapy alone. These women can therefore be spared the side effects of chemotherapy and still be confident of an excellent chance of cure.
Revolutionary breast cancer management
Traditionally, breast cancers have been characterised into biologically and clinically meaningful subgroups according to histological grade and type. But now, it has been recognised that breast cancer heterogeneity may be underpinned by myriad mechanisms of genetic abnormalities.
Attention to genetic mutation and testing has been given a significant boost in recent years, thanks to the “Angelina Jolie Effect”. This is the phenomenon in which the famous Hollywood star found out that she was a carrier of the BReast CAncer 1 (BRCA1) gene mutation and opted to undergo a preventive double mastectomy in 2013. BRCA1 and BRCA2 were the first two major susceptibility genes for breast cancer to be identified, in 1994 and 1995 respectively. A mutation in the BRCA1 or 2 gene results in a loss of the ability of cells to repair damaged DNA, leading to accumulation of altered genetic material that may eventually cause cells to transform into cancer. Hence, a carrier of BRCA1 or 2 gene mutations is at a much higher risk of developing breast and/or ovarian cancers. Interestingly, the same defect in DNA repair can also exploited as targets for drug treatment. A new group of drugs known as PPAR inhibitors have been found to be an effective treatment in breast and ovarian cancers with BRCA 1 or 2 mutations.
Evolving diagnostic and treatment techniques
There are new developments in diagnostic and treatment strategies to effectively target such subgroups of breast cancer, including advanced genetic tests for cancer screening, hormonal therapies and HER2-targeted therapy. Consequentially, oncologists now have more treatment options, which they could integrate into the most favourable course of treatment for the patient.
More than two-thirds of invasive breast cancers are hormone-sensitive and they respond well to hormonal therapy. Hormonal therapy acts mainly by decreasing the body’s production of estrogen, or blocking or destroying the hormone receptors in the cancer cells. They have been successfully used to:
- reduce the risk of cancer recurrence after surgery;
- shrink a tumour before surgery to increase the likelihood of the cancer being removed completely;
- decrease the risk of cancer developing in the other breast tissue; and
- slow down or stop the growth of cancer cells that have spread to other parts of the body.
The development of CDK 4/6 Inhibitors, a targeted agent with the potential to inhibit the enzyme that plays a key role in the proliferation of breast cancer cells, is yet another example of an evolution in breast cancer treatment. So, despite the exponential growth in the incidence of breast cancer, we can look on the bright side: breast cancer survival rates and the possibility of complete cures have improved significantly as well, thanks to earlier detection and cancer research breakthroughs over the last decade.
1 Singapore Cancer Registry Interim Annual Report 2011-2015