A5089866079- Advanced Breast Cancer Therapies
- Breast Cancer Treatment Studies
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- Fibroblast Growth Factor Research
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Metastasis and carcinoma case studies
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- Advanced Biosensing Techniques and Applications
- Immunotherapy and Immune Responses
- PARP inhibition in cancer therapy
- Estrogen and related hormone effects
- Radiomics and Machine Learning in Medical Imaging
- Breast Lesions and Carcinomas
- Epigenetics and DNA Methylation
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Ferroptosis and cancer prognosis
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
Dana-Farber Cancer Institute
2015-2024
Harvard University
2015-2024
Dana-Farber Brigham Cancer Center
2015-2024
Breast Cancer Research Foundation
2023
Conquer Cancer Foundation
2023
Susan G. Komen Breast Cancer Foundation
2023
Broad Institute
2017-2020
Brigham and Women's Hospital
2015-2020
Massachusetts General Hospital
2019
Massachusetts Institute of Technology
2017
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies content in 0.1× coverage whole-genome data without prior knowledge mutations. We apply ichorCNA to 1439 samples 520 patients with metastatic prostate or breast cancers. In earliest tested sample for each patient, 34% have ≥10% tumor-derived cfDNA, sufficient...
Mechanisms driving resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor-positive (HR+) breast cancer have not been clearly defined. Whole-exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate mechanisms including RB1 loss, activating alterations AKT1, RAS, AURKA, CCNE2, ERBB2, and FGFR2, loss estrogen receptor expression. In vitro experiments confirmed that these conferred resistance. Cancer cells cultured also acquired RB1, KRAS, or...
Abstract Intratumor heterogeneity is postulated to cause therapeutic resistance. To prospectively assess the impact of HER2 (ERBB2) on response HER2-targeted therapy, we treated 164 patients with centrally confirmed HER2-positive early-stage breast cancer neoadjuvant trastuzumab emtansine plus pertuzumab. was assessed pretreatment biopsies from two locations each tumor. heterogeneity, defined as an area ERBB2 amplification in >5% but <50% tumor cells, or a HER2-negative by...
•We analyzed mechanisms of resistance to PARP inhibitor/platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer.•Genomic reversion functional BRCA1/2 protein was identified one-half patients.•Up-regulation DNA end resection as a mechanism two additional patients.•RAD51 foci assessed by immunohistochemistry correlated with clinical response inhibitor/platinum.•RAD51 focus staining warrants further exploration biomarker for use. BackgroundLittle is known about poly(adenosine...
To identify clinically relevant mechanisms of resistance to ER-directed therapies in ER+ breast cancer.We conducted a genome-scale functional screen spanning 10,135 genes investigate whose overexpression confer selective estrogen receptor degraders. In parallel, we performed whole-exome sequencing paired pretreatment and postresistance biopsies from 60 patients with metastatic cancer who had developed ER-targeted therapy. Furthermore, experiments validate genes/pathways drug combinations...
Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect standard chemotherapy on immune microenvironment may suggest new opportunities for immunotherapy-based approaches treating HR+/HER2- tumors.HR+/HER2- tumors were analyzed before after neoadjuvant chemotherapy. sTIL assessed histologically; CD8+ cells, CD68+...
502 Background: HER2 targeted therapy without chemotherapy may be insufficient to completely eradicate a HER2+ cancer in cases of significant intratumor heterogeneity (ITH-HER2). Methods: We conducted single-arm phase II study enrolling centrally confirmed breast cancer. Pts received 6 cycles T-DM1 plus Pertuzumab before surgery. Central ITH-HER2 was assessed on baseline ultrasound-guided core biopsies from 2 distinct areas each tumor (3 cores/site). defined as at least one the six...
Importance Patients with early-stage ERBB2 (formerly HER2 )–positive breast cancer ( + BC) who experience a pathologic complete response (pCR) after receiving neoadjuvant therapy have favorable survival outcomes. Predicting the likelihood of pCR may help optimize therapy. Objective To test ability HER2DX assay to predict in patients BC are deescalated Design, Setting, and Participants In this diagnostic/prognostic study, was administered on pretreatment tumor biopsy samples from enrolled...
Abstract De-escalating adjuvant therapy following pathologic complete response (pCR) to an abbreviated neoadjuvant regimen in human epidermal growth factor receptor 2-positive (HER2+) breast cancer is the focus of international research efforts. However, feasibility this approach and its appeal patients providers had not been formally investigated. We aimed assess adherence de-escalated antibody doublet (trastuzumab pertuzumab [HP], without chemotherapy) among with pCR paclitaxel/HP (THP)....
Biomarkers to guide the use of pertuzumab in treatment early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple status are needed.
Abstract To evaluate the role of chemotherapy in stage IA triple-negative breast cancer, we conducted a retrospective population-based study including 8601 patients. The use significantly increased from 2010 to 2019 patients with T1b and T1c tumors ( p = 0.001 < 0.001, respectively). Receipt was associated improved cancer-specific survival (BCSS, adjusted hazard ratio 0.70; 0.006), particularly (5-year BCSS 94.5% vs. 91.2%).
Young age at breast cancer diagnosis correlates with unfavorable clinicopathologic features and worse outcomes compared older women. Understanding biological differences between tumors in young versus women may lead to better therapeutic approaches for younger patients.We identified 100 patients ≤35 years old nonmetastatic who participated the prospective Women's Breast Cancer Study cohort. Tumors were assigned a surrogate intrinsic subtype based on receptor status grade. Whole-exome...
Background Preclinical and clinical data support potential synergy between anti-HER2 therapy plus immune checkpoint blockade. The safety tolerability of trastuzumab emtansine (T-DM1) combined with pembrolizumab is unknown. Methods This was a single-arm phase Ib trial (registration date January 26, 2017) T-DM1 in metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Eligible patients had HER2-positive, metastatic cancer previously treated taxane, trastuzumab,...
BACKGROUNDHER2-targeting therapies have great efficacy in HER2-positive breast cancer, but resistance, part due to HER2 heterogeneity (HET), is a significant clinical challenge. We previously described that phase II neoadjuvant trastuzumab emtansine (T-DM1) and pertuzumab (P) trial early-stage none of the patients with HER2-HET tumors had pathologic complete response (pCR).METHODSTo investigate cellular molecular differences among according pCR, we performed RNA sequencing ERBB2 FISH 285...