Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
Humans ; Female ; Phthalazines/adverse effects* ; Piperazines/administration & dosage* ; Middle Aged ; Ovarian Neoplasms/genetics* ; Retrospective Studies ; Adult ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage* ; China ; Maintenance Chemotherapy ; BRCA2 Protein/genetics* ; Antineoplastic Agents/adverse effects* ; Progression-Free Survival ; BRCA1 Protein/genetics*

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.
BRCA1 Protein/genetics* ; BRCA2 Protein/genetics* ; Breast Neoplasms/pathology* ; Cross-Sectional Studies ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Mutation ; Recombinational DNA Repair ; Triple Negative Breast Neoplasms/pathology*

Asian Continental Ancestry Group ; BRCA1 Protein/genetics* ; Breast Neoplasms/surgery* ; China ; Female ; Genetic Testing ; Humans ; Mastectomy

Asian Continental Ancestry Group/genetics* ; BRCA1 Protein/genetics* ; China ; Consensus ; Humans

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

OBJECTIVETo investigate the knowledge and willingness of breast cancers patients from Shanghai for genetic counseling and gene testing.

METHODSA total of 428 patients filled out the questionnaire and the data was statistically analyzed.

RESULTSMost of the patients were unaware of genetic counseling and gene testing. But after a brief introduction, a majority of them were willing to accept genetic counseling and recommend their family members to participate. The willingness was education- and age-related. When told that gene testing may benefit themselves, 92.1% of the patients were willing to be tested. However, when told that gene testing may only benefit their family, only 33.9% of the patients were willing to join the testing. The acceptance was also age-, education- and family income-related. The difference was statistically significant. Moreover, the willingness ratio to participate the gene testing was lower than expected. Overall, 74.1% of the patients were willing to accept cheaper preliminary gene screening, whilst only 19.2% were willing to accept genetic testing of higher price. Despite of being told that testing results will be maintained as confidential, still 43.2% worried about adverse effects. Such patients tended to younger, from low-income families, with a family history of associated cancers, or personal history of other cancers. The difference was statistically significant.

CONCLUSIONThe majorities of patients do not know but are willing to accept genetic counseling and gene testing and recommend their family to participate. Lack of genetic knowledge, cost for the testing and concerns about discrimination are the obstacles for patients to participate in genetic counseling and gene testing. To spread the knowledge about breast cancer and establish a follow-up screening system for high-risk population may improve the tertiary prevention for breast cancer.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; statistics & numerical data ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Breast Neoplasms ; diagnosis ; ethnology ; genetics ; Chi-Square Distribution ; China ; Educational Status ; Female ; Genetic Counseling ; Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Social Class

No abstract available.
BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Base Sequence ; DNA/chemistry ; Databases, Genetic ; Female ; Hereditary Breast and Ovarian Cancer Syndrome/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

OBJECTIVETo explore the clinicopathologic characteristics and biological markers of breast carcinomas in young women.

METHODSImmunohistochemical SP method was used to study breast cancer susceptibility gene (BRCA1) and WWOX in breast carcinomas of patient ≤ 35 years of age (107 cases) and ≥ 60 years of age (112 cases). The findings were correlated with clinicopathological features. In addition, PCR amplification and direct sequencing were performed to detect the BRCA1 gene mutation of exons 2 and 20 using fresh frozen tissue samples in other 10 patients who were ≤ 35 years of age.

RESULTSThe positive rate of BRCA1 protein expression was higher in the young age group [65.4% (70/107)] than that of the old age group [35.7% (40/112)]. ER, PR, HER2, and WWOX protein expression and proliferation marker Ki-67 were no statistically different in the two groups (all P > 0.05). BRCA1 expression was significantly correlated with pTNM and axillary lymph node metastasis (both P < 0.05), but not with ER, PR, HER2 and WWOX protein expression (all P > 0.05). Ki-67 and histological grading showed no statistical correlation (P > 0.05). WWOX protein expression showed no correlation with clinicopathologic characteristics (all P > 0.05). Mutation of exons 2 and 20 of the BRCA1 gene was not detected in any of 10 cases studied.

CONCLUSIONBRCA1 cytoplasmic expression statistically correlates with the development and prognosis of breast cancer of young patients.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; BRCA1 Protein ; genetics ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; surgery ; Exons ; Female ; Genes, BRCA1 ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Middle Aged ; Mutation ; Neoplasm Staging ; Oxidoreductases ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Tumor Suppressor Proteins ; metabolism ; WW Domain-Containing Oxidoreductase ; Young Adult

Age of Onset ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Receptors, Progesterone ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer.

METHODSPrimary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated.

RESULTSThe BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively.

CONCLUSIONSBRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; BRCA1 Protein ; genetics ; metabolism ; CA-125 Antigen ; blood ; Carboplatin ; administration & dosage ; DNA-Binding Proteins ; genetics ; metabolism ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms, Glandular and Epithelial ; drug therapy ; metabolism ; surgery ; Ovarian Neoplasms ; drug therapy ; metabolism ; surgery ; Paclitaxel ; administration & dosage ; RNA, Messenger ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Tubulin ; genetics ; metabolism