Leigh Pate and Dr. Steffi Oesterreich had become close friends, and communicated often on how to partner researchers, clinicians and patient advocates. Together with other researchers and patient advocates they wrote a commentary putting forward a clear roadmap on how to make use of the unprecedented opportunity to drive forward multidisciplinary, multicenter and international collaborative research into ILC.
Using natural language processing, we screened more than 2 million de-identified patients records at UPMC in order to identify rare metastases to the eye. We identified 28 patients with orbital metastases, with a significant enrichment in patients with ILC. There was a trend that these metastases were more frequently bilateral, but less frequently co-occurring with metastases to the brain in ILC compared to NST, suggesting different routes of spread but larger studies combining data from multiple centers are necessary to confirm these findings.
We have had a number of productive collaborations with pharmaceutical companies, including Foundation Medicine. This study was the largest analysis of metastatic ILC at that point in time, and showed that mILC had an enrichment of NF1 mutations, and higher TMB (with APOBEC signature) compared to NST. Assessing sites of metastatic specimens showed fewer metastases in the liver and enrichment in reproductive sites, GI tract, omentum and bone marrow.
Limited availability of research models was a substantial barrier that at least partially accounted for the lack of research on ILC. Dr. Nilgun Tasdemir, a postdoc in the lab, performed a very elegant and thorough characterization of ILC cell lines – the start of our commitment to generate more ILC models faithfully representing different aspects of the disease. This project, with bioinformatics support from George Tseng, characterized 2D and 3D growth phenotypes of ILC cell lines. It emphasized how the unique morphology and cell–cell adhesion defects influence drug response and invasion, building a phenotypic framework for preclinical modeling.
Dr. Oesterreich was honored and excited to join The Cancer Genome Atlas Network (TCGA) working group performing the largest to date comprehensive molecular analysis of ILC. This landmark paper provided a comprehensive molecular portrait of ILC, highlighting distinct genomic and transcriptomic features compared to invasive ductal carcinoma (IDC). Dr. Oesterreich contributed key expertise in lobular biology, ensuring that ILC was well represented within TCGA analyses, reflecting a major collaborative effort among over 50 institutions. The study showed that 95% of ILC cases had alterations in CDH1, that there were differences in mutations frequency (for example in PTEN, AKT, FOXA1 and TBX3), and that there are molecular variants within ILC. The conclusion was that “ILC is a clinically and molecularly distinct disease”.
This foundational study established that invasive lobular carcinoma (ILC) cell lines exhibit unique estrogen-mediated transcriptional programs and distinct tamoxifen responses compared to ductal models. Led by Dr. Matthew Sikora during his postdoctoral training in the Oesterreich–Lee laboratory, the work included collaborations with multiple Pitt faculty and collaborators such as Dr. Alana Welm (Utah), providing the first systematic evidence for differential estrogen signaling in ILC. Dr. Sikora is now Associate Professor at UC and is continuing work on ILC.
Breast cancer science duo Steffi Oesterreich, PhD & Adrian Lee, PhD recruited to Pittsburgh from Baylor College of Medicine.
Dr. Oesterreich is again a member of the ILCS Organizing Committee, and as such helps to organize the 2024 ILCS in Leuven, Belgium.
Dr. Oesterreich, several members of the Lee-Oesterreich Lab, and future ILC Program of Excellence team member Dr. Priscilla McAuliffe join the 2023 ILC Symposium Organizing Committee, helping organize and run the 2023 ILCS, which returns to Pittsburgh, PA.”