Titles and Affiliations
Head of the Translational Breast Cancer Laboratory
Free University of Brussels
Research area
Finding new treatments for patients with high-risk, early-stage estrogen receptor-positive/HER2-negative breast cancer.
Impact
High-risk, early-stage estrogen receptor (ER)-positive/HER2-negative breast cancers (also called luminal B) are often harder to treat because they do not respond as well to chemotherapy or immunotherapy compared to other breast cancer subtypes, and many patients face a risk of recurrence after standard treatment. Prior research has shown that combining radiotherapy with immunotherapy can modulate the immune system in complex ways. Understanding these effects in detail is crucial for tailoring treatments to be more effective. To that end, Dr. Sotiriou is conducting the Neo-CheckRay clinical trial (NCT03875573), an innovative phase II study testing whether combining three treatments—chemotherapy, targeted radiation, and immunotherapy—can improve outcomes for this patient population. The overarching goal is to improve understanding of how tumor and immune cells interact under different treatments, to identify potential biomarkers of response, and ultimately to better tailor effective treatment combinations and improve outcomes for patients with early-stage ER-positive/HER2-negative breast cancer.
Progress Thus Far
Neo-CheckRay tests whether adding immunotherapy to standard chemotherapy plus a type of targeted radiation called stereotactic body radiotherapy (SBRT) can help the immune system fight cancer more effectively compared to chemotherapy and SBRT alone and increase the chance of a complete response before surgery. In the past year, Dr. Sotiriou and his team analyzed immune and tumor cells from breast tumors and lymph nodes of patients enrolled in the Neo-CheckRay clinical trial to understand how each treatment affects individual cell types. They found that SBRT can help the immune system recognize cancer. Importantly, stronger cancer-fighting immune responses and reduced immune suppression were observed in patients who received immunotherapy—especially the combination of durvalumab and oleclumab. These effects were not seen in the chemotherapy plus SBRT group alone. These findings help explain how treatments reshape the tumor environment and will guide the team’s next steps to uncover which patients are most likely to benefit from these therapies.
What’s next
In the upcoming year, Dr. Sotiriou and his team will finish processing and analyzing tumor and lymph node samples from the remaining patients enrolled in the Neo-CheckRay trial. They will also begin analyzing surgery samples including normal breast tissues from the participants to serve as a healthy reference point. In addition, the team will analyze data from T and B cell receptors—key parts of the immune system that recognize and respond to cancer. This will add to our understanding of which immune cells are becoming more active in response to treatment and whether these changes are linked to better outcomes. Using this larger and more complete dataset, the team will take a deeper look at how immune cells develop and interact over time, how different immune and support cells (like fibroblasts) change their function during and after treatment, and how they communicate with each other inside the tumor environment. Finally, the team will use genetic tools to compare cancer cells to healthy tissue and study whether specific cancer cell groups are more likely to spread or resist treatment.
Biography
Christos Sotiriou, MD, PhD earned a medical degree from the Université Libre de Bruxelles, Belgium, in 1993. He did his internal medicine/oncology residency at the Institut Jules Bordet and earned his specialty in this field in July 1999. From October 1999 through September 2001, he worked as basic research fellow, at the Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. After having completed a PhD Thesis at the Université Libre de Bruxelles in September 2004, he became “Chercheur Qualifié” (Research Faculty Member – tenured position) at the National Foundation for Scientific Research (FNRS, Belgium) in 2005. In March 2010, he took over the lead of the Breast Cancer Translational Research Laboratory J-C Heuson. In October 2013, he was appointed “Maître de Recherche” (Senior Research Associate – tenured position) by the National Foundation for Scientific Research (FNRS, Belgium), and also one of the “Chefs de Clinique” (Heads of clinic) at the Medical Oncology Clinic of the Institut Jules Bordet.
Dr. Sotiriou is a full member of ASCO, AACR, and ESMO, an Elected Member of the Scientific Council of the International Agency for Research on Cancer (World Health Organisation (2012 – 2016), and an Elected Fellow of the European Academy of Cancer Sciences (since 2010), which is hosted under the auspices of European CanCer Organization (ECCO). He is also Advisory Council Member of the Susan G. Komen for the Cure (since June 2010).
Dr. Sotiriou is reviewer for several high impact peer-reviewed journals. He has been elected associated editor of the Annals of Oncology Journal (Breast tumors) (January 2014-December 2015). Internationally renowned researcher, author, and co-author of over 160 peer-reviewed articles, Dr. Sotiriou is focusing his research on genomics in breast cancer.
