BRCA mutations

Human epidermal growth factor receptor-2 (HER2)-targeting drugs are increasingly being incorporated into therapeutic paradigms for non-breast cancers, yet studies on HER2 expression in ovarian cancer (OC) are inadequate. Here, we studied the HER2 status and dynamic changes in OC by reviewing the records of patients who underwent HER2 testing at a single institution. Clinical parameters, including histology, BRCA status, and immunohistochemistry (IHC), were evaluated alongside HER2 expression, timing, and anatomical location...

Whole genome doublings (WGD), a hallmark of human cancer, is pervasive in breast cancer patients. However, the molecular mechanism of the complete impact of WGD on survival and treatment response in breast cancer remains unclear. To address this, we performed a comprehensive and systematic analysis of WGD, aiming to identify distinct genetic alterations linked to WGD and highlight its improvement on clinical outcomes and treatment response for breast cancer. A linear regression model along with weighted gene co-expression network analysis (WGCNA) was applied on The Cancer Genome Atlas (TCGA) dataset to identify critical genes related to WGD...

KEY CLINICAL MESSAGE: In a patient with metastatic breast cancer, an acquired BRCA mutation in the BRCA gene was detected, resulting in benefits from olaparib treatment. This underscores the importance of ongoing genetic phenotype testing after paclitaxel chemotherapy. ABSTRACT: Triple-negative breast cancer (TNBC) is associated with a poor prognosis and elevated mortality risk. BRCA mutations are commonly regarded as prevalent mutations in TNBC patients, strongly associated with congenital familial heredity...

PURPOSE: We compared 21-gene recurrence score (RS) distribution and expression of the single-gene/gene groups within this assay between BC patients with pathogenic variants (PV) in BRCA1/2 vs the general 21-gene-tested BC population. METHODS: This retrospective study included consecutive 21-gene-tested female ER + HER2-negative BC patients with germline PVs in BRCA1/2. RS/gene expression data were compared to a previously described commercial use database (CDB, N = 799,986)...

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han...

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Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in various tumors. A significant therapeutic challenge with either ICIs or PARP inhibitors as monotherapy is treatment failure from intrinsic primary resistance or the development of secondarily acquired resistance after a period of responsiveness. The combination of PARP inhibitors and ICIs could mitigate this by potentiating treatment response. We describe an 83-year-old male patient who initially presented with abdominal pain, and weight loss along with alternating constipation and diarrhea...

Male breast cancer (MBC) is a rare entity, underrepresented in population studies and clinical trials, resulting in management of MBC to be informed by current research on female breast cancer (FBC). A literature review was conducted by accessing relevant articles on 2 databases, by searching keywords "male breast cancer". A total of 29 articles from year 2011 to 2022 were selected for this review. The authors found that male breast cancer generally occurs later in life with higher stage, higher grade, and more estrogen receptor (ER) positive tumours...

Human epidermal growth factor receptor 2 (HER2)-targeted therapy has transformed the treatment paradigm for early-stage HER2-positive breast cancer, providing personalized and effective interventions. This comprehensive review delves into the current state of HER2-targeted therapies, emphasizing pivotal clinical trials that have demonstrated their substantial impact on long-term outcomes. Combination therapies that integrate HER2-targeted agents with chemotherapy exhibit enhanced tumor responses, particularly in neoadjuvant settings...

OBJECTIVE: We aimed to revalidate the chemotherapy response score (CRS) system as a prognostic factor for ovarian cancer patients with breast cancer gene ( BRCA ) mutations or those receiving frontline poly-ADP ribose polymerase (PARP) inhibitors or bevacizumab as maintenance therapy. METHODS: A retrospective analysis was performed using medical records of patients with high-grade serous carcinoma who received neoadjuvant chemotherapy followed by interval debulking surgery between January 2007 and December 2021 at 5 tertiary medical institutions in South Korea...

OBJECTIVES: Given the high response to platinum based chemotherapy in BRCA 1/2 mutated high grade serous ovarian cancers, there is uncertainty about the relative benefits of primary cytoreductive surgery versus neoadjuvant chemotherapy in this population. We aimed to compare the survival outcomes for women with BRCA 1/2 mutated high grade serous ovarian cancers undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy. METHODS: We conducted a retrospective cohort study of all stage III/IV BRCA mutated high grade serous ovarian cancers treated with primary cytoreductive surgery or neoadjuvant chemotherapy at a single tertiary cancer center between 1991 and 2020...

BACKGROUND: Breast cancer (BC) is the primary cause of cancer mortality. Herein, we aimed to establish and verify a prognostic model consisting of endoplasmic reticulum stress and apoptosis related genes (ERAGs) to predict patient survival. METHODS: The Cancer Genome Atlas (TCGA) database was used to download gene expression and clinical data to identify the differentially expressed genes (DEGs). Using univariate Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis, the prognostic ERAGs were screened...

Ten percent of patients with breast cancer, and probably somewhat more in patients with ovarian cancer, have inherited germline DNA mutations in the breast and ovarian cancer genes BRCA1 and BRCA2 . In the remaining cases, the disease is caused by acquired somatic genetic and epigenetic alterations. Targeted therapeutic agents, such as poly ADP-ribose polymerases (PARP) inhibitors (PARPi), have emerged in treating cancers associated with germline BRCA mutations since 2014. The first PARPi was FDA-approved initially for ovarian cancer patients with germline BRCA mutations...

Triple-negative breast cancer (TNBC) poses a serious therapeutic challenge due to the occurrence of frequently aggressive, heterogenic, and metastatic tumours. The absence of therapeutic targets for traditional therapies is a hindrance to establishing a standardised therapy for TNBC. There is limited TNBCs epidemiological and real-world data about TNBC treatment regimens in Poland. We retrospectively analysed clinical data from our hospital registry from 2015 and 2020. A total of 8103 individuals with breast cancer were admitted to the MSCI, while 856 (10...

Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers. We also aimed to identify population specific BRCA1/2 mutation hotspots, to enable the development of more affordable testing strategies...

INTRODUCTION: Breast cancer is the leading cause of neoplasm mortality among women. Several prevention strategies have been implemented to early detect and prevent the cancer occurrence. The most effective protocol includes prevention mastectomy for the high-risk patients. In our study, we have compared the efficacy of subcutaneous mastectomy (SCM) and skin sparing mastectomy (SSM) in long-term follow up. METHODS: We have included 201 female patients who have been treated at our department over the course of 20 years between 2000 and 2019...

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(1) Background: Somatic and germline alterations can be commonly found in prostate cancer (PCa) patients. The aim of our present study was to perform a comprehensive review of the current literature in order to examine the impact of BRCA mutations in the context of PCa as well as their significance as genetic biomarkers. (2) Methods: A narrative review of all the available literature was performed. Only "landmark" publications were included. (3) Results: Overall, the number of PCa patients who harbor a BRCA2 mutation range between 1...

Loss-of-function mutations in the Breast Cancer Susceptibility Gene (BRCA1 and BRCA2) are often detected in patients with breast cancer. Poly(ADP-ribose) polymerase-1 (PARP1) plays a key role in the repair of DNA strand breaks, and PARP inhibitors have been shown to induce highly selective killing of BRCA1/2-deficient tumor cells, a mechanism termed synthetic lethality. In our previous study, a novel PARP1 inhibitor─( E )-2-(2,3-dibromo-4,5-dimethoxybenzylidene)- N -(4-fluorophenyl) hydrazine-1-carbothioamide (4F-DDC)─was synthesized, which significantly inhibited PARP1 activity with an IC50 value of 82 ± 9 nM...

About 50% of High Grade Serous Ovarian Cancer exhibit a high degree of genomic instability due to mutation of genes involved in Homologous Recombination (HRD) and such defect accounts for synthetic lethality mechanism of PARP inhibitors (PARP-i). Several clinical trials have shown how BRCA and HRD mutational status profoundly affect first line chemotherapy as well as response to maintenance therapy with PARP-i, hence Progression Free Survival and Overall Survival. Consequently, there is urgent need for the development of increasingly reliable HRD tests, overcoming present limitations, as they play a key role in the diagnostic and therapeutic process as well as have a prognostic and predictive value...