Education & Training
- Ph.D. -Humboldt University- Berlin, Germany-1992
- PostDoc-UT Health Science Center-San Antonio, TX
Research Interest Summary
We are studying how estrogen receptor positive tumor cells become resistant to endocrine therapy. This includes the analysis of genetic and epigenetic changes, using cell line and animal models, as well as clinical samples. Our current effort is focused on the characterization of hotspot mutations in the estrogen receptor, the main target for the endocrine therapy. Its ligand binding domain is mutated in approximately 20-40% of patients with metastatic ILC. We are aiming to generate and characterize models for ER-mutant disease, understanding mechanism of resistance, and finally therapeutic approaches to prevent and treat ER-mutant metastases.
We also have a significant effort in increasing understanding of the second most frequent histological subtype of breast cancer, called invasive lobular breast cancer. It accounts for 10-15% of all breast cancer (~24-36,000 annually), and ranks as the 6th most common cancer in women. Although the incidence of invasive ductal cancer (IDC) has remained relatively constant over the last two decades, there has been a significant increase in the number of cases of ILC. Despite showing better prognostic and predictive factors (e.g. more often ER+/PR+, and lower levels of the proliferation marker Ki67), patients with ILC have worse long-term outcome compared to IDC. This paradox has not been studied, and in general there is a striking lack of molecular studies of ILC. We set out to specifically study the etiology of ILC, its response to hormone therapy, and mechanisms for progression into metastatic disease, with the hypothesis that a better understanding of this subtype will lead to more effective therapies and improved patient outcomes.
All of our studies are done in close collaboration with experts in bioinformatics, medical oncology, pathology, and statistics.
Oesterreich S, Davidson NE. The search for ESR1 mutations in breast cancer. Nat Genet. 2013 Dec; 45(12):1415-6 PMID: 24270445
Sikora MJ, Cooper KL, Bahreini A, Luthra S, Wang G, Chandran UR, Davidson NE, Dabbs DJ, Welm AL, Oesterreich S. Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response. Cancer Res. 2014 Mar 1; 74(5):1463-74. PMID: 24425047
Pathiraja TN, Nayak SR, Xi Y, Jiang S, Garee JP, Edwards DP, Lee AV, Chen J, Shea MJ, Santen RJ, Gannon F, Kangaspeska S, Jelinek J, Issa JP, Richer JK, Elias A, McIlroy M, Young L, Davidson NE, Schiff R, Li W, and Oesterreich S. Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer. Science Transl Med. 2014 Mar 26; 6(229):229ra41.PMID: 24670685
Liao S, Hartmaier RJ, McGuire KP, Puhalla SL, Luthra S, Chandran UR, Ma T, Bhargava R, Modugno F, Davidson NE, Benz S, Lee AV, Tseng GC, Oesterreich S.The molecular landscape of premenopausal breast cancer. Breast Cancer Res. 2015 Aug 7;17:104. doi: 10.1186/s13058-015-0618-8.PMID: 26251034.
Kim S, Oesterreich S, Kim S, Park Y, Tseng GC.Integrative clustering of multi-level omics data for disease subtype discovery using sequential double regularization.Biostatistics. 2016 Aug 22. pii: kxw039. [Epub ahead of print]. PMID 27549122
Zhu L, Ding Y, Chen CY, Wang L, Huo Z, Kim S, Sotiriou C, Oesterreich S, Tseng GC. MetaDCN: meta-analysis framework for differential co-expression network detection with an application in breast cancer. Bioinformatics. 2016 Dec 28. pii: btw788. doi: 10.1093/bioinformatics/btw788. [Epub ahead of print] PMID: 28031185
Wang P, Bahreini A, Gyanchandani R, Lucas PC, Hartmaier RJ, Watters RJ, Jonnalagadda AM, HTrejo Bittar HE, Berg A, Hamilton RL, Kurland BF, Weiss KR, Mathew A, Leone JP, Davidson NE, Nikiforova MN, Brufsky AM, Ambros TF, Stern AM, Puhalla SL, Lee AV, Oesterreich S. Sensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions and cell free DNA of breast cancer patients. Clinical Cancer Research. 2016 Mar 1;22(5):1130-7. PMCID: PMC477540
Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Hayat S, Lester SC, Tse GMK, Factor RE, Collins, LC, Allison KH, Chen YY, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack A, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, The Cancer Genome Atlas Network, and Perou CM. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163, 506-519.2015