MedicalResearch.com Interview with:
Jian Jin, Ph.D.
Mount Sinai Endowed Professor in Therapeutics Discovery
Professor, Department of Pharmacological Sciences
Professor, Department of Oncological Sciences
Director, Mount Sinai Center for Therapeutics Discovery
Co-leader, Cancer Clinical Investigation Program, Tisch Cancer Institute
Icahn School of Medicine at Mount SinaiMedicalResearch.com: What is the background for this study? Response: Triple-negative breast cancer (TNBC), a subtype of breast cancer that lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), represents 12-20% of all breast cancers. TNBC has poor prognosis, high recurrence, a low survival rate, and has higher incidence in African-American and Hispanic women. Currently, there are no effective therapies for treating a substantial portion of TNBC patients.
Enhancer of zeste homolog 2 (EZH2) is the main enzymatic subunit of the polycomb repressive complex 2 (PRC2) which catalyzes trimethylation of histone H3 lysine 27 (H3K27me3) to promote transcriptional silencing. EZH2 is overexpressed in multiple types of cancer including triple negative breast cancer (TNBC) and high expression levels correlate with poor prognosis. Several EZH2 inhibitors which inhibit the enzymatic activity of EZH2 have shown promise in treating sarcoma and follicular lymphoma in clinics. However, current EZH2 inhibitors are ineffective at blocking proliferation of TNBC cells even though they effectively inhibit the enzymatic activity of EZH2. While the proteolysis targeting chimera (PROTAC) technology for selective degradation of the target protein has been rapidly gaining momentum in the drug discovery field, the hydrophobic tagging approach for selective protein degradation has received considerately less attention from the scientific community.(more…)
MedicalResearch.com Interview with:Aditya Bardia, MBBS, MPH
Director, Precision Medicine, Center for Breast Cancer,
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston, MA 02114
MedicalResearch.com: What is the background for this study? Response: Metastatic triple negative breast cancer is associated with aggressive tumor biology, and tends to affect younger patients and African Amerians. The response rate with standard chemotherapy regimens in patients with pre-treated metastatic TNBC ranges from 10-15%, and median progression-free survival ranges from 3-4 months. The median survival of metastatic TNBC is around 12 months and has not changed in the past 20 years. Thus, treatment of metastatic triple negative breast cancer represents an unmet clinical need. (more…)
MedicalResearch.com Interview with:Roshni Rao, M.D
University of Texas Southwestern
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Triple negative breast cancer (TNBC) is characterized by not having estrogen, progesterone, or Her2Neu receptors. Although a less common type, it is aggressive, and leads to a disproportionate number of deaths from breast cancer.
TNBC is more common in young, African American women, but can be found in other ethnic groups as well.
This study performed mitochondrial DNA (mtDNA) analysis, to evaluate for patient genetic ancestry, in 92 patients with TNBC. In regards to self-identified ethnicity, there were 31 African-Americans, 31 Whites, and 30 Hispanics. Utilizing mtDNA, 13% of patients had discordance between self identified ethnicity and mtDNA analysis. Discordance was highest in the Hispanic group. The Hispanic patients were also much younger at initial age of diagnosis, and less likely to have a family history of breast cancer. Ancestry from Nigeria, Cameroon, or Sierre Leone were most common in the African-Americans with triple negative breast cancer.
MedicalResearch.com Interview with:
Melinda L. Telli, M.D. Assistant Professor of Medicine Stanford University Division of Medical Oncology Stanford, CA 94305-5826Medical Research: What is the background for this study? What are the main findings?
Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA damaging therapeutics. A second major goal was to identify predictors of response to this platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC).
Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR). This compares favorably to pCR rates commonly observed with anthracycline and taxane-based regimens in this group of patients. The response rate was higher among triple-negative breast cancer patients with a germline BRCA1 or BRCA2 mutation (56%).
Given the hypothesis of underlying DNA repair defects in sporadic triple-negative breast cancer, we also evaluated a novel measure of genomic instability to detect the accumulation of changes in the genomic landscape of a tumor attributable to defective homologous recombination DNA repair. Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. (more…)
Privacy & Cookies Policy
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.