29 October 2015
A*STAR findings on breast cancer hold potential for new treatments.
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Singapore - Scientists at the Bioinformatics Institute (BII) and Genome Institute of Singapore (GIS), research institutes under the Agency for Science, Technology and Research (A*STAR), have made discoveries that could lead to new ways of diagnosing and treating breast cancer. The scientists from both institutes used large-scale genomic data of breast cancers, demonstrating the use of computational techniques to increase understanding of diseases and improve patient treatments.

Breast cancer is the most frequent cancer diagnosed amongst women, with an estimated 1.67 million new cancer cases worldwide in 2012 1. In Singapore, more than 9,000 women were diagnosed with breast cancer between 2010 and 2014 2. Breast cancer is also the leading cause of cancer death in females locally.

Improving classification and treatment of prevalent type breast cancer

The BII scientists identified and characterised two 3 new major classes of invasive ductal carcinoma (IDC), which comprise about 80% of all breast cancers. The increased knowledge of these genetically and clinically distinct classes will improve the diagnosis, prognosis and treatment of IDC, paving the way for personalised treatment with better patient outcomes (See Annex A).

Employing integrative bioinformatics and analyses, the scientists found that the intermediate grade (histologic grade 2) - assigned to approximately 50% of IDC cases - did not exist at the molecular level. IDC tumours in this grade would be better classified under the two major classes described, to enable better prediction of disease outcomes and for optimal treatment to be assigned.

Identifying new targets for treatment of aggressive breast cancer

In a separate study, scientists from GIS discovered a molecular mechanism that can be targeted to treat a more aggressive type of breast cancer, called triple-negative breast cancer (TNBC). The researchers identified a crucial protein whose increased activity promotes breast cancer metastasis and resistance to paclitaxel, a first line chemotherapeutic agent to treat breast cancer.

Additionally, treating this pathway may also contribute to the prevention of tumour recurrence, which is the main reason for breast cancer patient mortality.

While increased awareness of the need for early detection has led to improved survival in breast cancer patients, the development of improved treatment strategies remains important to further reduce mortality rates.

Dr Benjamin Seet, Executive Director of A*STAR’s Biomedical Research Council, said, “These findings advance our understanding of breast cancer, which is the most common cancer affecting women in Singapore. More importantly, it allows us to develop precise and effective treatment strategies for these particular types of breast cancer, as well as to discover new drugs for the patients who do not get better.”




Invasive Ductal Carcinoma (IDC), as with many other malignant tumours, is very heterogeneous 4. Histological grading, which entails the microscopic study of cellular structure and function, classifies tumours into three grades which reflect the aggressiveness of tumours. This method is widely adopted by oncologists as a factor for prognosis and assignment of therapy. However, for intermediate grade (Grade 2) tumours, this method of evaluation is highly subjective, with as little as 50% agreement between observers in some cases 5 and little understanding of its molecular basis.

Using integrative bioinformatics and analyses of data from more than 1,200 patients, the BII scientists found that a 22-gene panel could be used to classify IDC cases into two new major classes that reflect the aggressiveness of the tumours, namely Low Genetic Grade (LGG) and High Genetic Grade (HGG). Cancers in each of these classes demonstrated distinct genomic alterations and differences in the way they develop, marking a shift in understanding by suggesting that IDC does not necessarily follow a gradual progressive model of disease.

Dr Lee Soo Chin, Senior Principal Investigator at the Cancer Science Institute of Singapore and Senior Consultant at the National University Cancer Institute, Singapore (NCIS), commented on the significance of these findings, "While Grade 1 and Grade 3 tumours clearly represent tumours belonging to two ends of a spectrum with distinctly different aggressiveness, the clinical relevance of a Grade 2 tumour is less certain, making the information less useful when making therapeutic decisions in the clinic. In this study, investigators from BII classified breast cancers into two new genetic subclasses, removing the intermediate group of histological Grade 2, which have distinctly different survival and different genetic aberrations, and can be a useful classification to use in the clinic when validated."

The 22-gene panel could thus be used to complement or replace the histological grading prediction system, improving clinical practice with better molecular characterisation of tumours in either class. The 22- gene panel, together with other genetic and functional features of these two IDC molecular classes identified by the BII team, could serve as novel prognostic and therapeutic biomarkers that could lead to the development of personalised systemic therapies using drugs that are already available.

Dr Vladimir Kuznetsov, Senior Principal Investigator at BII who led the study said, "These findings demonstrate the continuing importance of basic sciences and specifically, integrative genomic studies in understanding the molecular basis of cancer aggressiveness to improve treatment of cancer patients. We hope that the global research community can harness the power of big genomic data analysis in innovative ways to improve healthcare."

Correspondence should be addressed to Vladimir A Kuznetsov,
Genome and Gene Expression Data Analysis Division,
A*STAR Bioinformatics Institute, 30 Biopolis Street, #07-01, Singapore 138671.

Full text of "Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development" can be accessed online here .


  1. International Agency for Research on Cancer, "GLOBOCAN 2012 Fact Sheet".
  2. Singapore Cancer Registry, Interim Annual Report Trends in Cancer Incidence in Singapore 2010 2014
  4. Tumour heterogeneity refers to the differences between tumours of the same type within patients, and between cancer cells within a tumour. Such diversity makes it challenging to classify the tumors and design effective treatment strategies.
  5. American Cancer Society, CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29.

(Top image: Primary tumour, Bottom image: Recurrent tumour)

The images show a higher level of phosphorylated IRAK1 in recurrent tumour compared to that in the original primary tumour.

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