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Breast Cancer Translational Research

​Research PI:
​Associate Professor Yap Yoon Sim

a) Research focus, goals and research activities (focusing on lab’s technical expertise) 

Our research focuses on unmet needs and unanswered questions that are clinically relevant in breast cancer. Breast cancer is the most common cancer among women worldwide and in Singapore, where it is the leading cause of cancer death. Ethnic differences in breast cancer remains poorly understood; ethnic disparities in outcomes here in Singapore need to be addressed and eradicated urgently from a multifaceted approach. Apart from interrogating the standard clinicopathological characteristics and treatment factors, to understand why outcomes have persistently been worse in Malay patients, we seek to decipher differences in tumour biology driving the adverse disease trajectory. 

Giving the right treatment at the right time, to the right patient, is another research theme. Our biomarker research also includes liquid biopsies, that may be useful to detect and predict outcomes and guide treatment. We aim to dissect the heterogeneity of breast cancer, and to develop better strategies to treat the disease. De-escalation of treatment may be appropriate for some patients, while escalation with novel regimens may be required for others. 

Our phase II investigator-initiated trial on Lenvatinib and Pembrolizumab in Endocrine Resistant Breast Cancer with Letrozole in the Advanced setting (LaPemERLA; NCT05286437) is based on supporting preclinical efficacy. We aim to develop an effective immunotherapy combination strategy for treatment-resistant metastatic luminal breast cancers, which are typically “immune-cold”. Accrual is currently ongoing, with over half of the target number of patients enrolled so far. We have been banking blood, tissue and faecal specimens in this clinical trial, and are also generating patient-derived breast cancer models in collaboration with other researchers in NCCS. 

b) Role in NCCS research ecosystem to improve patient outcomes 

Using the data and tissue from our patients, we strive to improve our understanding of breast cancer biology to give the right treatment to the right patients. With several collaborations within and beyond Singapore, our research is aligned with the NCCS’ bench to bedside and back research focus. 

Selected publications (latest and most impactful from 2019 onwards) 

  1. Tan RS WSO, Lee KH, Park S, Iqbal J, Park YH, Lee JE, Yu JH, Lin CH, Lu YS, Ono M, Ueno T, Naito Y, Onishi T, Lim GH, Tan SM, Lee HB, Koh J, Han W, Im SA, Tan VKM, PHYU N, Wong FY, Tan PH, Yap YS. Outcomes in non-metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative pure mucinous breast cancer. Journal of the National Comprehensive Cancer Network In press; 2024 
  2. Prat A, Solovieff N, Andre F, O'Shaughnessy J, Cameron DA, Janni W, Sonke GS, Yap YS, Yardley DA, Partridge AH, Thuerigen A, Zarate JP, Lteif A, Su F, Carey LA. Intrinsic subtype and overall survival of patients with advanced HR+/HER2- breast cancer treated with ribociclib and ET: correlative analysis of MONALEESA-2, -3, -7. Clin Cancer Res. 2024 Feb 16;30(4):793-802. 
  3. Chiu J, Su F, Joshi M, Masuda N, Ishikawa T, Aruga T, Zarate JP, Babbar N, Balbin OA, Yap YS. Potential value of ctDNA monitoring in metastatic HR + /HER2 - breast cancer: longitudinal ctDNA analysis in the phase Ib MONALEESASIA trial. BMC Med. 2023 Aug 15;21(1):306. 
  4. Tan RS, Ong WS, Lee KH, Lim AH, Park S, Park YH, Lin CH, Lu YS, Ono M, Ueno T, Naito Y, Onishi T, Lim GH, Tan SM, Lee HB, Ryu HS, Han W, Tan VKM, Wong FY, Im SA, Tan PH, Chan JY, Yap YS. HER2 expression, copy number variation and survival outcomes in HER2-low nonmetastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC Analysis. BMC Medicine 2022 Mar 17;20(1):105. 
  5. Yap YS, Lu YS, Tamura K, Lee JE, Ko EY, Park YH, Cao AY, Lin CH, Toi M, Wu J, Lee SC. Insights Into Breast Cancer in the East vs the West: A Review. JAMA Oncol. 2019;5(10):1489-1496. Interplay between intrinsic and extrinsic factors in shaping host and tumor characteristics, which result in different outcomes. (Yap YS. Outcomes in breast cancer-does ethnicity matter? ESMO Open. 2023 Jun;8(3):101564.)

Interplay between intrinsic and extrinsic factors in shaping host and tumor characteristics, which result in different outcomes. (Yap YS. Outcomes in breast cancer-does ethnicity matter? ESMO Open. 2023 Jun;8(3):101564.)