Steffi Oesterreich, PhD, is a researcher at UPMC Hillman Cancer Center who focuses her work on better understanding how to most effectively treat breast cancers, including invasive lobular carcinoma (ILC) and estrogen receptor-positive (ESR1) breast cancer resistant to hormonal therapies. The team also has a large research focus on breast cancer metastases.
Invasive Lobular Carcinoma
ILC is the most common special histological subtype of breast cancer, following invasive ductal carcinoma (IDC)/no special type (NST). ILC is the sixth most common cancer type in women making up 10-15% of all breast cancer diagnoses.
Though the incidence of IDC has remained stable over the last two decades, incidence of ILC has significantly increased. And, even though patients with ILC typically show better prognostic and predictive factors, those patients have worse long-term outcomes compared to patients with IDC.
Clinically, there are many differences between ILC and IDC. Due to the lack of firm or distinct lumps with ILC, imaging technologies tend not to work as well, and it is typically more difficult to diagnose. In addition, patterns of how the cancer spreads differ. Metastasis to the lungs is decreased in patients with ILC compared to IDC, while metastasis to the ovary and peritoneum is increased.
Yet, patients with the two different subtypes of breast cancer are typically treated similarly. Data have shown that their treatment mechanisms may be different, opening the door for more targeted therapies for patients with ILC.
Dr. Oesterreich and her team are working to genomically profile tumors from patients with ILC. Their ultimate goal is to create high-efficacy therapies specifically targeting the pathways activated in ILC.
ESR1 Mutant Breast Cancers
About two-thirds of all breast tumors, regardless of subtype, have estrogen receptors (ER) that drive the growth of tumor cells. There are multiple therapeutic approaches that target ER very effectively. These therapies cure most patients with estrogen receptor positive breast cancer, but some patients do not respond, or stop responding, and the cancer spreads.
Dr. Oesterreich and others have found that about one-third of those who are not responsive have mutations in the ER gene, called “ESR1.” The prevalence of these mutations has paved the way for researchers to determine the role these changes in the genome play in metastasis and disease progression.
“We have shown that breast tumors with such hotspot mutations not only become resistant to endocrine therapies but also show an enhanced ability to metastasize,” says Dr. Oesterreich. “Several studies have collectively shown that such tumors are more aggressive, and patients, unfortunately, suffer from worse outcomes in the metastatic setting.”
Though this is discouraging for cancer prognosis, it leads to the possibility of more effective therapies, such as tumor infiltrating macrophages — a type of white blood cell. Some macrophages support tumor formation, while others counteract the formation of tumors. There is increasing evidence that tumor-supporting macrophages could be targeted as a form of immunotherapy, but additional studies are necessary.
“I am a basic/translational scientist who has built a career dedicated to breast cancer research — defining mechanisms of oncogenesis, disease progression, and resistance to therapy,” says Dr. Oesterreich. “In order to make the greatest progress toward the goal of understanding these mechanisms, I seek broad collaborations and thrive on working with transdisciplinary teams. Working across disciplinary boundaries, we are poised to gain new knowledge to better treat breast cancers”. Dr Oesterreich also actively works with a number of breast cancer advocacy organizations and independent advocates within the US and in Europe.
About Dr. Oesterreich
Dr. Oesterreich is the Shear Family Foundation Chair in Breast Cancer Research and Professor of pharmacology at the University of Pittsburgh. She is co-leader of the Cancer Biology program and co-directs the Women’s Cancer Research Center, a collaboration between the UPMC Hillman Cancer Center and Magee Womens Research Institute.
Her lab work is done with Adrian Lee, PhD, in the Lee/Oesterreich Laboratory. Their lab focuses on the molecular basis of breast cancer development and resistance to therapy — aiming to improve precision medicine and outcomes for breast cancer patients.
Dr. Oesterreich has authored more than 200 scientific articles on breast cancer, and her research has been funded by Susan G. Komen, Breast Cancer Research Foundation, the National Cancer Institute, and other sources.
Oesterreich S, Nasrazadani A, Zou J, et al. Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer [published online ahead of print, 2022 Oct 14]. J Natl Cancer Inst. 2022;djac157. doi:10.1093/jnci/djac157
Elangovan A, Hooda J, Savariau L, Puthanmadhomnarayanan S, Yates ME, Chen J, Brown DD, McAuliffe PF, Oesterreich S, Atkinson JM, Lee AV. Loss of E-cadherin Induces IGF1R Activation and Reveals a Targetable Pathway in Invasive Lobular Breast Carcinoma. Mol Cancer Res. 2022;20(9):1405-1419. doi:10.1158/1541-7786.MCR-22-0090
Tasdemir N, Ding K, Savariau L, Levine KM, Du T, Elangovan A, Bossart EA, Lee AV, Davidson NE, Oesterreich S. Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma. Sci Rep. 2020;10(1):11487. Published 2020 Jul 13. doi:10.1038/s41598-020-68141-9
Du T, Zhu L, Levine KM, Tasdemir N, Lee AV, Vignali DAA, Houten BV, Tseng GC, Oesterreich S. Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism. Sci Rep. 2018;8(1):7205. Published 2018 May 8. doi:10.1038/s41598-018-25357-0
See more of Dr. Oesterreich’s publications.
Written By: Annaliese Daniels
Reviewed By: Steffi Oesterreich