A5078936208- Cancer Treatment and Pharmacology
- Breast Cancer Treatment Studies
- Advanced Breast Cancer Therapies
- BRCA gene mutations in cancer
- Epigenetics and DNA Methylation
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Health, Environment, Cognitive Aging
- Genetic Syndromes and Imprinting
- Cancer Genomics and Diagnostics
- Chronic Lymphocytic Leukemia Research
- Ferroptosis and cancer prognosis
- Nutrition, Genetics, and Disease
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Multiple and Secondary Primary Cancers
- Genetic factors in colorectal cancer
- Computational Drug Discovery Methods
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Chemotherapy-induced cardiotoxicity and mitigation
- Cancer Immunotherapy and Biomarkers
- Estrogen and related hormone effects
Smilow Cancer Hospital
2025
Yale Cancer Center
2022-2024
Yale University
2020-2024
Aging is a leading risk factor for cancer. While it proposed that age-related accumulation of somatic mutations drives this relationship, likely not the full story. We show aging and cancer share common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro tested on clinical tissues. This termed CellDRIFT, increased with age across multiple tissues, distinguished tumor normal tissue, was escalated breast tissue...
Abstract Background There is currently no clinical trial data regarding the efficacy of everolimus exemestane (EE) following prior treatment with CDK4/6 inhibitors (CDK4/6i). This study assesses use and in patients metastatic HR+ HER2− breast cancer previously treated endocrine therapy (ET) or + CDK4/6i. Methods Retrospective analysis electronic health record-derived for from 2012 to 2018. The proportion receiving EE first-line, second-line, third-line, median duration next line (TTNT) by...
PURPOSE To investigate the clinical behavior of breast cancer in young BRCA carriers according to specific gene ( BRCA1 v BRCA2 ) and association timing genetic testing (before at diagnosis) with prognosis. METHODS This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) or , who were diagnosed stage I-III invasive 40 years younger between January 2000 December 2020 78...
Age is one of the strongest risk factors for development breast cancer, however, underlying etiology linking age and cancer remains unclear. We have previously observed links between epigenetic aging signatures in breast/tumor tissue risk/prevalence. However, these DNA methylation-based biomarkers capture diverse phenomena it not known to what degree they relate risk, and/or progression.Using six clocks, we analyzed whether distinguish normal adjacent tumor (cases) vs from healthy controls...
De novo oligometastatic breast cancer, a unique disease needing new treatment paradigms.
1104 Background: De novo oligometastatic breast cancer (oligo-mBC) is generally defined as < 5 lesions at the time of diagnosis and represent a steadily increasing subset metastatic cancers. Several retrospective studies demonstrated prolonged overall survival (OS) for select patients with oligo-mBC when treated multimodality therapy (chemotherapy, surgery, radiation). However, randomized trials that tested surgical resection primary tumor, or radiation oligometastases (including...
Abstract Background: The current standard of care is to treat all patients with metastatic breast cancer palliative intent, regardless extent disease. However, in real world practice oligometastatic disease are sometimes treated surgery and/or radiation/ablation combination systemic therapy render them as having no evidence Previous randomized clinical trials have not shown a benefit adding or radiation cancer, however, these had small number HER2+ patients. uniquely responsive chemotherapy...
Abstract Background: Retrospective studies suggest that patients with oligometastatic breast cancer (≤ 5 metastatic lesions) have improved prognosis and may benefit from multimodality treatment. Randomized clinical trials, however, mostly recurrent not shown this approach. Real-world data on de novo stage IV (oligo-stage IV) disease are limited. We therefore investigated differences in 5-year mortality oligo-stage vs extensive-stage who received curative palliative chemotherapy at our...
Abstract Background: CDK4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) is standard first line (1L) treatment for metastatic hormone positive (ER/PR+) HER2- negative breast cancer (mBC). Some patients have progression free survival (PFS) of 2 years or more whereas some very short PFS on these medications. Thymidine kinase a biomarker that reflects cell proliferation. DiviTum®TKa an assay was cleared by the FDA in July 2022 based data showed thymidine activity (TKa) value &lt; 250...
Abstract Aging is the leading risk factor for cancer. While some have proposed that age-related accumulation of somatic mutations drives this relationship, it likely not full story. Here, we show both aging and cancer share a common epigenetic replication signature, which modeled from DNA methylation data in extensively passaged immortalized human cells vitro tested on clinical tissues. This signature – termed CellDRIFT increased with age across multiple tissues, distinguished tumor normal...
576 Background: It’s incompletely understood why some women without germline breast cancer predisposing mutations develop early onset cancer. Breast in young is often more aggressive, with high histologic grade, worse prognosis, and higher risk of recurrence. We hypothesize that these have somatic the normal tissue contribute to tumorigenesis. Methods: Whole exome sequencing (WES) data was analyzed from adjacent tumor compared matched peripheral blood (n=28). All patients were <50yo, had...
Abstract Background: In 2012 the FDA approved everolimus and exemestane (EE) as second line therapy for patients who have progressed on letrozole or anastrozole, based BOLERO-2 trial which showed improvement in PFS with EE compared to alone (6.9 vs 2.8 months). Currently, aromatase inhibitors (AI), fulvestrant (F), combination a CDK4/6 inhibitor (CDK4/6i) are most commonly used first endocrine therapies hormone receptor (HR) positive HER2 negative metastatic breast cancer (mBC). There is...
Abstract Background: There is an incomplete understanding of why some women develop breast cancer 20-25 years earlier than the majority women. Only 30-40% with high risk family history are found to have known predisposing mutations. This phenomenon referred as “missing heredity”. We hypothesize that high-risk but no penetrance mutations who at a young age higher deleterious load germline functional impact (gHFI) single nucleotide variants in relevant genes. Methods: 94 diagnosed &lt;50...
Abstract Background It is unclear how many of genes contribute to the biology cancer. We hypothesize that interact with core cancer gene (CCG) in a protein-protein interaction network (PPI) may have functional importance. Methods categorized into 1- (n=6791), 2- (n=7724), 3- (n=1587), and >3-steps (n=362) removed from nearest CCG STRING PPI demonstrate cancer-biology related contribution these different neighborhood categories decreases as their distance CCGs increases. Results Genes...
Abstract Purpose: Age is one of the strongest risk factors for development breast cancer, however underlying etiology linking age and cancer remains unclear. We have previously observed links between epigenetic aging signatures in breast/tumor tissue risk/prevalence. However, these DNA methylation-based biomarkers capture diverse phenomena it not known to what degree they relate risk, and/or progression. Methods: Using six clocks, we analyzed whether distinguish normal adjacent tumor (cases)...