The LFS Association is proud to announce that our most recent grant was awarded to Professor Arnie Levine at the Institute for Advanced Studies in honor of Thierry Frébourg. Pr. Levine and his collaborators seek to determine if the immune system is responding to breast cancer in Li-Fraumeni syndrome patients and what type of immune cells may be responding. Knowing the particulars of an immune response in TP53 driven LFS-breast cancers may lead to a better understanding of which immunotherapies to utilize to treat patients and possibly lead to new and more effective therapies.
The grant to Pr. Levine and colleagues was awarded in honor of Professor Thierry Frébourg. Thierry served as chapter chair for LFSA – France and he passed away suddenly and unexpectedly this past March. Pr. Frébourg was a true asset to the global community as a major contributor to cancer genetic research and Li-Fraumeni syndrome. Thierry’s boundless energy, dedication, and smile will be forever ingrained in our souls.
Spontaneous breast cancers, with no known inherited predispositions, are classified into several different types of cancers: hormone responsive breast cancers (HRBC) with estrogen and/or progesterone receptors promoting abnormal growth of cells with no or few TP53 mutations, HER-2BC with that cellular growth receptor promoting cancerous growth (HER-BC), and triple negative breast cancers (TNBC) that have none of those three growth promoting alterations but commonly have a spontaneous genetic alteration in the TP53 gene that contributes to cancerous growth and abnormal replication of cells. About 70% to 90% of women with Li-Fraumeni syndrome and an inherited TP53 gene alteration develop breast cancers. These are commonly HRBC, with or without HER-growth receptors, but they always have an altered inherited TP53 gene (LFS-BC). Thus, Li-Fraumeni breast cancers differ from spontaneous breast cancers not only in their very early age of onset, commonly 20-40 years of age, but also by the presence of both HRBC properties and TP53 gene alterations. The reason this classification is so useful is that it determines the optimal treatment to regress or eradicate these different cancers. For example, spontaneous TNBC with TP53 mutations have many types of immune cells (lymphocytes) infiltrating the cancers (called tumor infiltrating lymphocytes or TIL cells), and checkpoint immunotherapy can be used to treat these cancers, whereas spontaneous HRBCs have very few TILS and rarely respond to immunotherapies. At present, we know nothing about the immune system’s response to Li-Fraumeni Syndrome breast cancers. This proposal has as its goal to determine what types of immune cells, if any, populate LFS-BCs. The proposed experiments are designed to determine if the immune system is able to kill some of the LFS breast cancer cells. Further, this proposal will explore the inherited and spontaneous genetic alterations found in a number of LFS-BCs from different patients and look for patterns that could be useful for treatment with existing therapies. These technologies, that determine the properties of the immune system that can destroy tumors, termed multiplex immune-histo-chemistry, have been successfully developed and applied over the past 7-10 years for spontaneous breast and lung tumors. This proposed study will now apply these tests to Li-Fraumeni breast cancers, in the hope that they can be followed by the development of new therapies for these cancers.
Next LFSA Grant Cycle
September 1 – Call for Letters of Intent
September 30 – Deadline for Letters of Intent
October 15 – Notification to selected individuals to submit a full grant proposal
November 30 – Deadline for grant proposals (invited proposals only from Oct 15 notifications)
December 21 – Awarding of grant
The Letter of Intent form will be available here on September 1, 2021.