The majority of breast cancers are diagnosed as breast cancer of no specific type (or ductal carcinoma), a heterogeneous category of tumors that includes curable neoplasms as well as highly aggressive cancers. This classification is inadequate for clinical management of breast cancer patients as well as for designing laboratory and clinical research protocols. Although there are clearly a number of different tumor phenotypes within this diagnostic category, traditional morphology and even current molecular markers of prognosis are incapable of clearly discriminating different subtypes of ductal cancer from one another. In this project, we propose to distinguish biologically different groups of ductal breast cancer from one another using gene expression profiles. This is based on the concept that gene expression profiles represent an objective and quantitative measure of a neoplasm's phenotype. We have in preliminary experiments identified a number of genes that are differentially expressed among different ductal cancers, consistent with our hypothesis that will use a custom breast cancer array that we developed to represent the genes most capable of differentiating breast cancers, and then use this array to analyze gene expression profiles in microdissected breast cancer samples. Groups of tumors that share expression profiles identified through cluster analysis of data will then be examined for pathological and clinical similarities to develop more specific hypothesis of ductal cancer classification. Finally, we will design case-control studies to test and refine these classification hypotheses. Through this stepwise development and testing of classification hypotheses, we expect to identify biologically distinctive categories of breast cancer. A sound molecular classification of this nature will greatly benefit clinical management of breast cancer patients and will provide a useful reference for the design of breast cancer research.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
United States
Zip Code
Lo, Pang-Kuo (2018) FOXF2 differentially regulates expression of metabolic genes in non-cancerous and cancerous breast epithelial cells. Trends Diabetes Metab 1:
Cravero, Karen; Medford, Arielle; Pallavajjala, Aparna et al. (2018) Biotinylated amplicon sequencing: A method for preserving DNA samples of limited quantity. Pract Lab Med 12:e00108
Connolly, Roisin M; Fackler, Mary Jo; Zhang, Zhe et al. (2018) Tumor and serum DNA methylation in women receiving preoperative chemotherapy with or without vorinostat in TBCRC008. Breast Cancer Res Treat 167:107-116
Connolly, Roisin M; Li, Huili; Jankowitz, Rachel C et al. (2017) Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study. Clin Cancer Res 23:2691-2701
Lo, Pang-Kuo (2017) The controversial role of forkhead box F2 (FOXF2) transcription factor in breast cancer. PRAS Open 1:
Haffner, Michael C; Esopi, David M; Chaux, Alcides et al. (2017) AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination. Nat Commun 8:142
Sunay, Melek M E; Foote, Jeremy B; Leatherman, James M et al. (2017) Sorafenib combined with HER-2 targeted vaccination can promote effective T cell immunity in vivo. Int Immunopharmacol 46:112-123
Parsons, Heather A; Beaver, Julia A; Cimino-Mathews, Ashley et al. (2017) Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer. Clin Cancer Res 23:379-386
Cidado, Justin; Wong, Hong Yuen; Rosen, D Marc et al. (2016) Ki-67 is required for maintenance of cancer stem cells but not cell proliferation. Oncotarget 7:6281-93
Lo, Pang-Kuo; Lee, Ji Shin; Liang, Xiaohui et al. (2016) The dual role of FOXF2 in regulation of DNA replication and the epithelial-mesenchymal transition in breast cancer progression. Cell Signal 28:1502-19

Showing the most recent 10 out of 282 publications