Evaluating Targets In Localized And Advanced Breast Cancer By Sequencing Tumor Dna At Diagnosis And After Progression (Elsa)

Background: Breast cancer therapy exerts strong selection pressure that shapes the evolution of the cancer. Despite the importance of these treatment-induced changes for the success of subsequent therapy, tumors have been rarely resampled and reanalyzed, with the exception of hematopoietic malignancies. The availability of next generation sequencing (NGS) has made it possible to get highly accurate sequencing that allows detection of mutations and other genetic alterations not only from tumor biopsies but also from circulating DNA fragments. Objectives: To demonstrate the evolution of the molecular genotype of breast cancer as patients are diagnosed, treated, and upon relapse. This will be accomplished by NGS of the tumor at key time points during the natural history of the disease. The molecular profile at diagnosis will be compared to the profile at recurrence/metastasis and after treatment for metastasis. Correlation with treatment response and adverse clinical outcomes will be determined. Study Design and Eligibility: We have initiated a prospective observational study in patients with a new diagnosis of Stage I, II and III breast cancer and an ECOG performance status of 0, 1 or 2. Patients should be medically suitable to give informed consent for a biopsy or surgical procedure. Enrollment will occur at community-based cancer centers with inclusion of under-served populations. Methodology: Tumor samples and blood samples are collected at - initial diagnosis/definitive surgery, first local relapse, diagnosis of metastasis and at first progression after treatment for metastatic disease. Molecular genotype will be analyzed from the tumor samples and from the circulating tumor DNA (ctDNA) in blood samples at each of the time points. ctDNA will also be assessed on blood samples collected annually till the diagnosis of metastasis and then more frequently at 3-6 month intervals in patients with high risk breast cancer. Statistical Design/Size of study sample: Formal sample size calculations are not required for this study as by design, it is based on participation. There is no discrete endpoint that can be powered by sample size calculation for this study. We are screening all patients who are diagnosed with breast cancer at our facility. The proposed enrollment is 300 patients per year. The study launched in December 2015 at 4 of our community-based cancer centers. Current enrollments is 46 patients. Citation Format: Gaba AG, Powell SF, Jennifer WL, Megan LL, Chun-Hung C, Lora BJ, Ford JM. Evaluating targets in localized and advanced breast cancer by sequencing tumor DNA at diagnosis and after progression (ELSA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-16.