Breast Research Programme

The breast research team in Pathology ACP focuses on 3 main themes of investigation - breast fibroepithelial lesions, triple negative breast cancers, and ductal carcinoma in situ of the breast.

Fibroepithelial lesions encompass the common fibroadenoma and the less frequently encountered phyllodes tumour. The phyllodes tumour resembles the fibroadenoma, although it is associated with a higher likelihood of recurrence in accordance with its grade, with recurrence rates for benign, borderline and malignant phyllodes tumours being 10%, 15% and 20% to 30% respectively (1,2). Malignant phyllodes tumours also possess metastatic potential, and there is a dismal prognosis once metastasis occurs.  We devised a nomogram that helps predict recurrence in an individual patient diagnosed with phyllodes tumour (2). Our team in collaboration with Professor Teh Bin Tean's laboratory discovered a novel mutation in the MED12 gene in fibroadenomas, which lends insight into tumourigenesis of this group of fibroepithelial neoplasms (3). We have also recently published data on the molecular genetics of progression of phyllodes tumours in collaboration with co-investigators from NCCS and Duke-NUS (4).

Triple negative breast cancers are a heterogeneous group of tumours that pose management challenges. They are usually high grade with poorer prognosis. We have pathologically characterised a large cohort of triple negative breast cancers from our Departmental archives (5,6), and are currently interrogating their genetic profiles using the nanostring technique, with focus on immune response genes (7).

Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of invasive disease. Many cases are detected on mammographic screening due to accompanying microcalcifications. While high grade DCIS tends to progress to invasion in a shorter time frame, low grade lesions are also not entirely innocuous. As factors that predict recurrence and invasion are still being debated, our group is interested in determining pathological and biological markers that are able to assist in clinical stratification (8,9).

Apart from these research themes, our group also collaborates on multiple investigations on the biology of breast disease with local and overseas investigators.

Reference:

1. Tan PH, Jayabaskar T, Chuah KL, Lee HY, Tan Y, Hilmy M, Hung H, Selvarajan S,Bay BH. Phyllodes tumors of the breast: the role of pathologic parameters. Am J Clin Pathol. 2005 Apr;123(4):529-40.


2. Tan PH, Thike AA, Tan WJ, Thu MM, Busmanis I, Li H, Chay WY, Tan MH; Phyllodes Tumour Network Singapore. Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol. 2012 Jan;65(1):69-76.


3. Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M,Ong KW, Tan BK, Rozen SG, Tan PH, Tan P, Teh BT. Exome sequencing identifieshighly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014 Aug;46(8):877-80.


4. Tan J, Ong CK, Lim WK, Ng CC, Thike AA, Ng LM,  Rajasegaran V, Myint SS, Nagarajan S, Thangaraju S, Dey S, Nasir ND, Wijaya GC, Lim JQ, Huang D, Li Z, Wong BH, Chan JY, McPherson JR, Cutcutache I, Poore G, Tay ST, Tan WJ, Putti TC, Ahmad BS, Iau P, Chan CW, Tang AP, Yong WS, Madhukumar P, Ho GH, Tan VK, Wong CY, Hartman M, Ong KW, Tan BK, Rozen SG, Tan P, Tan PH, Teh BT . Genomic landscapes of breast firbroepithelial tumors. Nat Genet. 2015 Nov 47(11):1341-45.


5. Thike AA, Iqbal J, Cheok PY, Chong AP, Tse GM, Tan B, Tan P, Wong NS, Tan PH. Triple negative breast cancer: outcome correlation with immunohistochemical detection of basal markers. Am J Surg Pathol. 2010 Jul;34(7):956-64.


6. Thike AA, Cheok PY, Jara-Lazaro AR, Tan B, Tan P, Tan PH. Triple-negative breast cancer: clinicopathological characteristics and relationship with basal-like breast cancer. Mod Pathol. 2010 Jan;23(1):123-33.


7. Matsumoto H, Koo SL, Dent R, Tan PH, Iqbal J. Role of inflammatory infiltrates in triple negative breast cancer. J Clin Pathol. 2015 Mar 6. [Epub ahead of print]


8. Wong FY, Wang F, Chen JJ, Tan CH, Tan PH. Outcomes of low-risk ductal carcinoma in situ in Southeast Asian women treated with breast conservationtherapy. Int J Radiat Oncol Biol Phys. 2014 Apr 1;88(5):998-1003.


9. Thike AA, Iqbal J, Cheok PY, Tse GM, Tan PH. Ductal carcinoma in situ associated with triple negative invasive breast cancer: evidence for a precursor-product relationship. J Clin Pathol. 2013 Aug;66(8):665-70.