May 31, 2016 02:06PM - edited Aug 12, 2018 10:12PM by JohnSmith
For decades, ILC has been chronically understudied and poorly understood, so this meeting is a BIG deal and a major step towards improving outcomes, since it brings together ILC researchers, scientists, oncologists, patients and advocates for the first time ever.
We will have an opportunity to share patient perspective issues with the Oncology community during the Advocacy portion of the meeting, so please compile a list of your ILC questions and concerns.
With that in mind, I've compiled a list, from my perspective as a caretaker to a Stage II Lobular patient.
Here's those questions (in no particular order).
1. What is being done for metastatic / Stage IV ILC?
2. What should be done for premenopausal ILC?
(Tamoxifen resistance; SOFT clinical trial ILC vs. IDC subtype analysis, etc)
There are zero studies!
3. What can be done to improve imaging diagnostics, both Pre & Post-diagnosis? (FDG-PET scans can generate "false negatives").
More specifically, where are the clinical trials that evaluate next generation imaging systems for post-diagnosis surveillance?
4. Liquid biopsies are an attractive, non-invasive method for the detection, evaluation, and monitoring of cancer progression. Since ILC imaging is often inconclusive, how can they be used to gauge ILC status, which may include any of the following:
---> monitoring therapy success, especially in clinical trial settings.
---> measuring mutational load (tumor mutational burden or TMB); i.e. volume of circulating tumor DNA (ctDNA), cell free DNA (cfDNA)
---> detection of cancer antigens / neoantigens, which may be exploited by next-generation Immunotherapy
Are these blood based biopsies being optimized for ILC?
5. Despite the dogma that says breast cancer, especially Hormone-fueled (ER+) disease, is not very immunogenic, how can Immunotherapy (CAR-T, Adoptive Cell Therapy, Checkpoint inhibitors, Vaccines, Oncolytic virus, etc) be harnessed for ILC?
With CAR-T, are there any unique ILC cell-surface Antigens/Neoantigens that can be targeted by genetically engineered T-Cells?
Who, if any, are the ILC researchers exploring Immuno-Oncology?
6. Combination therapy, despite the toxicity profile, is the most effective existing therapeutic approach.
What combo's are theorized to be most effective for ILC? What is on the horizon?
7. With so many labs working on endocrine resistance (PI3K, ESR1, TGFβ, WNT4, etc), what is the latest promising approach to overcome resistance in ILC?
When will science develop a diagnostic test to determine who is at higher risk for resistance?
8. An ongoing issue across the Oncology industry is cancer patient data is stuck in silo's. It's not being shared among researchers. Given the complexity and heterogeneity that large genomic studies are revealing, there's a thought that Big Data analysis may be able to identify mutational patterns, if the sample size is large enough. Since ILC is less common, this issue of data being sequestered is exacerbated.
What infrastructure or platform exists among institutions that allows sharing of ILC data, yet still maintains security and patient privacy?
9. Is there any effort to create an ILC tissue bank, which would accelerate discoveries?
Can the ILC research community tap into the tissue being collected by the MBCproject (Broad Institute / Dana-Farber research initiative)?
Genomic Health, the makers of the Oncotype DX test, is rumored to have 30,000 ILC tissue samples. Is it a crazy notion to think that they re-banked the tissue and would be willing to share it with ILC researchers?
10. How can we educate and encourage ILC patients on the importance of participating in these tumor tissue projects?
11. We need more ILC advocacy. Who are the existing ILC advocates? Is an organized advocacy group needed? RESOLVED! https://lobularbreastcancer.org/ has been established. Thank you!
12. Would the ILC community benefit by having a central website, housing all of the research studies, papers, latest news, progress, trials, events, upcoming meetings, theories, etc?
13. Now that recent studies (TCGA, Jules Bordet, METABRIC, etc.) have elucidated on the unique molecular characteristics of ILC, how can we exploit this info to launch clinical trials and which existing trials might benefit metastatic patients?
14. Some clinical trials fail due to lack of patient enrollment. Considering the under-representation of ILC, how can we ensure these trials are adequately enrolled? (e.g. Pitt ILC biomarker trial)
15. How can we encourage newly diagnosed patients to enroll in the Pitt ILC biomarker trial? (https://clinicaltrials.gov/ct2/show/NCT02206984) Locations enrolling ILC patients include: 1. Magee Womens Hospital of UPMC (Pittsburgh, Pennsylvania), 2. Mayo Clinic (Rochester, Minnesota), 3. MD Anderson (Houston, Texas)
16. Which, if any, historical Phase III clinical trials are worth mining for ILC vs. IDC subtype analysis?
17. Biomarkers: Beyond the ER, PR, HER2 biomarkers, research continues to tie ILC with over-expression of other receptors such as the Androgen receptor (AR), Prolactin receptor (PRLR), etc
What is the research status of these newer biomarkers?
What is the status of these biomarkers in clinical trials?
What therapies can theoretically target them?
18. Genomic studies continue to show a vast amount of mutational heterogeneity. What "omics" studies (Proteomics, the study of proteins; Transcriptomics, the study of RNA transcripts; Metabolomics, the study of cellular metabolism, etc.) have been done that yield a better landscape and elucidate common ILC targets?
19. Is anyone working on re-engineering the CDH1 gene so E-Cadherin functions properly, or is this still a lab concept? Assuming this is ever achieved, what are the theoretical outcomes? Would this eliminate the cancer or simply change the cancer phenotype?
20. Many theorize that cancer evolves, progresses, and metastases from a sub-population of cells known as cancer stem cells (CSCs). They are also referred to as tumor initiating cells or progenitor cells. What is being done to identify these cells related to ILC?
21. Are there any Stage IV ILC survivors (exceptional responders) that have achieved a durable remission using conventional therapies? If so, what can we learn from them?
22. All solid tumors have a Tumor MicroEnvironment (TME). The TME contains numerous immune-suppressive factors that coax the cells that surround the tumor to protect itself against the immune response. For example, Regulatory T cells (Tregs) are part of the TME and are necessary to prevent autoimmunity, but excessive Treg function contributes to cancer progression by inhibiting anti-tumor immune responses. Another way to describe this is using the "Seed and Soil" analogy. Cancer cells are seeds. Your body is the soil. Seeds often spread to distant organs BUT whether or not the cancer grows depends on the soil (the TME). It's complex, but evidence suggests that the TME determines ones fate. Immunotherapy drugs are considered soil therapies. They change the conditions of the soil, allowing your immune cells (T-Cells, B-Cells, NK cells, Macrophages, etc) to eradicate the cancer.
What do we know about the ILC TME that is unique and how can this be exploited?
23. During mid 2016, a $1.5 million donation for ILC research was made to Dana Farber / Harvard.
For details, see page 5 of the following pdf file.
How can we raise more money to fund ILC research? Can we establish a central hub for donations?
- As patients and caretakers, what can we do to help researchers push the needle of progress forward?
From your perspective, what issues need to be addressed?