Hunter Gaudio - Dr. Elemento, Dr. Cristofanilli - Week 7

 This past week, I began working on a data analysis project focused on differentiating inflammatory from non-inflammatory breast cancer utilizing a liquid biopsy data set. Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer (BC) that differs significantly from non-inflammatory BCs in presentation and prognosis. While rare in the general population, IBC is more prevalent in the Ashkenazi Jewish population (of which there is a very large population in NYC). This is partially because Ashkenazi Jewish people are much more likely (~1:40 as opposed to ~1:500 for general pop.) to have germline mutations (BRCA1 and BRCA2) that genetically predispose them to developing more aggressive forms of cancer. However, in the clinic, we are seeing an increased number of patients with Ashkenazi Jewish heritage and IBC, without BRCA1 and BRCA2 mutations. Given that Dr. Cristofanilli employs a variety of liquid biopsy tests in the clinic, our lab has built a large, longitudinal data set for this patient population that may enable the development of a molecular diagnostic test, which would be quite impactful as currently, IBC is only diagnosed clinically based on physical examination of the skin of the breast. Differentiating between inflammatory and non-inflammatory breast cancer at a cellular and genetic level in the circulation would enable the non-invasive and early diagnosis of IBC. This is important because IBC is often misdiagnosed as dermatitis. This is quite dangerous because IBC usually progresses within weeks to months as opposed to months to years in non-inflammatory BC. Therefore, spending weeks on wrongly prescribed antibiotics is quite harmful to the patient. Additionally, prognosis for IBC is much worse, and lymphatic involvement has been shown to be a driver in its aggressive and efficient metastasis. In addition to early diagnosis, a better understanding of the mutational and cellular profiles in the circulation for this disease can lead to better therapeutic response analysis and minimal residual disease monitoring. 

So far, we have seen that there is no statistically significant difference between cellular (circulating tumor cells (CTCs), tumor-derived extracellular vesicle (tdEVs), CTC clusters, and HER2+ CTCs) and genetic (ctDNA variations) between IBC and non-IBC patients within each molecular subtype (HER2+, HER2- HR+, HER2- HR-). From these preliminary results and from past work we have realized that the cellular information may be more correlated with prognosis and metastatic involvement and that genetic expression may be more relevant than genetic variation when it comes to differentiating between IBC and non-IBC. This understanding is currently shaping our next steps for the project, which may include differential methylation analysis (genetic expression) and a secondary prognostic model utilizing cellular data. 

On Tuesday, half of the BME program presented their Summer Immersion experiences/research, and Tuesday and Thursday were busy days in the clinic. Next week, I will present my experience and research at our weekly BME meeting and will continue to work on this IBC differentiation project.