Clinical application of PARP inhibitors in breast cancer / 国际肿瘤学杂志

Poly adenosine diphosphate ribose polymerase (PARP) inhibitors lead to synthetic lethality in homologous recombination repair-deficient (HRD) tumors by inhibiting DNA damage repair. Two PARP inhibitors, olaparib and talazoparib, have been approved for the salvage treatment of breast cancer susceptibility gene (BRCA) mutation, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer, and adjuvant treatment of early breast cancer. PAPR inhibitor single agent shows good antitumor activity and controllable safety. A number of clinical studies on PAPR inhibitors combined with chemotherapy, radiotherapy, antiangiogenic therapy and immunotherapy are being carried out. The indications of PARP inhibitors also extend from BRCA mutation to HRD, from ovarian cancer and breast cancer to other solid tumors, promising to benefit more patients in the future.

Genetic susceptibility genes and clinical features of early-onset breast cancer / 国际肿瘤学杂志

Objective:To explore the germline mutation frequency of genetic susceptibility genes and clinical characteristics in early-onset breast cancer (onset age ≤35 years) in China.Methods:Clinical information and peripheral blood of 150 patients aged 35 and younger diagnosed with breast cancer in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to December 31, 2019 were collected. Then DNA was extracted to detect germline mutations in breast cancer susceptibility gene (BRCA) 1, BRCA2, ataxia telangiectasia mutated (ATM) , partner and localizer of BRCA2 (PALB2) , tumor protein 53 (TP53) and cell cycle checkpoint kinase 2 (CHEK2) genes. Mutations were interpreted as pathogenic, likely pathogenic, uncertain significance, likely benign and benign according to the classification criteria and guidelines for genetic variation. Patients were divided into mutation group ( n=18) and non-mutation group ( n=132) according to the presence or absence of pathogenic or probable pathogenic germline mutations, and the χ2 test was used to analyze the relationships between genetic susceptibility gene mutations and clinicopathological characteristics. Results:Eighteen pathogenic or likely pathogenic germline mutations were detected in 150 patients with early-onset breast cancer, for an overall mutation frequency of 12.0%. Among them, there were 8 (5.3%) BRCA2 mutation, 7 (4.7%) BRCA1 mutation, 1 (0.7%) PALB2 mutation, and 2 (1.3%) TP53 mutation. There were no pathogenic or likely pathogenic variants in ATM and CHEK2 genes. The mutation type was dominated by frameshift mutation (9/18, 50.0%) , followed by nonsense mutation (7/18, 38.9%) , missense mutation (1/18, 5.6%) and splice acceptor mutation (1/18, 5.6%) . Among the molecular subtypes of 18 mutation carriers, 9 cases were Luminal B, 6 cases were triple negative breast cancer (TNBC) , 2 cases were Luminal A, and only 1 case was human epidermal growth factor receptor-2 (HER-2) amplification. Among them, 8 BRCA2 mutation carriers were Luminal type, and 6 of 7 BRCA1 mutation carriers were TNBC type. There were no statistical differences in family history of breast cancer ( P=0.343) , estrogen receptor (ER) status ( χ2=0.16, P=0.688) , HER-2 status ( χ2=2.89, P=0.089) , molecular subtype ( χ2=1.99, P=0.575) , and initial diagnosis TNM stage ( χ2=2.49, P=0.115) between the mutation group and the non-mutation group. Conclusion:The patients with early-onset breast cancer have high frequency of germline mutations. It is recommended that patients with early-onset breast cancer undergo genetic counseling and multigene testing.

Blood biomarkers for breast cancer screening and early diagnosis / 国际肿瘤学杂志

Breast cancer screening is an economical, effective, and simple screening measure for asymptomatic people to achieve the goals of early detection, early diagnosis and early treatment. Existing screening methods are mainly based on breast cancer X-rays and ultrasound, which are less sensitive to early lesions and cannot assess the risk of breast cancer in asymptomatic people. Breast cancer susceptibility genes, DNA methylation, microRNAs and circulating tumor cells, as blood biomarkers for breast cancer screening and early diagnosis, can identify high-risk breast cancer populations and improve the early diagnosis rate of breast cancer.

Antibody-drug conjugates in HER2-positive breast cancer / 中华医学杂志(英文版)

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

Interpretation of guidelines for the diagnosis and treatment of breast cancer during the COVID-19 outbreak / 中国肿瘤临床

The worldwide outbreak of a novel coronavirus (COVID-19) in December 2019 significantly affected the routine diagnosis and treatment of breast cancer due to resource and staffing constraints. In addition, breast cancer patients have poor immunity and are, therefore, more susceptible to COVID-19. If they are infected, the risk of severe illness is extremely high. Therefore, finding a balance between the effective prevention and control of COVID-19 and diagnosing and treating patients with breast cancer is a significant clinical issue during the pandemic. Therefore, the National Cancer Quality Control Center Breast Cancer Expert Committee brought together experts to urgently compile a "Guideline for the Rationalized Diagnosis and Treatment of Breast Cancer during the Outbreak of Corona Virus Disease 2019". Here, we will interpret the core recommendations in the guideline for breast cancer diagnosis and treatment.

Clinicopathologicai characteristics and susceptibility genes of early-onset breast cancer / 国际肿瘤学杂志

Early-onset breast cancer has aggressive clinicopathological characteristics and worse prognosis.However,there are few studies about it at home and abroad,which restricts the improvement of diagnosis and treatment level of breast cancer.Compared with older breast cancer,early-onset breast cancer has high mutation frequency and wide mutation spectrum.The study of unique susceptibility genes of early-onset breast cancer not only helps elucidate the difference of germline mutation spectrum between early-onset breast cancer and older breast cancer,but also will be helpful to study the diagnostic and prognostic marker for breast cancer,which provides evidence for screening and precision therapy.

Bladder tissue engineering scaffold：its application and vascularized strategies / 中国组织工程研究

BACKGROUND:Along with the increasing improvement of bladder tissue engineering research, the vascularization of tissue-engineered bladder after implantation becomes an issue of concern. OBJECTIVE: Combined with relevant literature in recent years, to review the choice, design and application of scaffold materials for bladder tissue engineering as wel as vascularized strategies folowing implantation. METHODS:The first author retrieved PubMed database and CNKI databases for articles relevant to biological scaffold materials in bladder tissue engineering and vascularization of tissue-engineered bladder published between January 2000 to September 2014 using the keywords of “tissue engineering; bladder; biomaterials/scaffolds; vascularization” in English and Chinese, respectively. RESULTS AND CONCLUSION: Recently, the biological scaffolds for bladder tissue engineering include two main categories: natural biomaterials and synthetic polymers. The major target of bladder tissue engineering remains to prepare the best cel-seeded scaffolds, to determine the best source of stem cels, to explore the best differentiation way of stem cels, and to promote angiogenesis and nerve regeneration of implanted scaffolds. Thereinto, promoting vascularization of scaffold materials and building complex tissues is most chalenging. At present, it is stil difficult to precisely control the directional proliferation, migration and differentiation of the attached endometrial cels. Although the vascular network is necessary for the nutrient supply and metabolic waste removal of cels or tissues, strategies to promote angiogenesis or vasculogenesis are stil limited.

Adipose-derived stem cells for repair of urinary system injury:current situation and problems in application / 中国组织工程研究

BACKGROUND:Although there is no report of adipose-derived stem cells in ureteral repair, but with the deepening of the research of adipose stem cells, the differentiation conditions of adipose-derived stem cells to the vascular endothelial cells, smooth muscle cells and urothelial cells are more mature, and the experimental research of adipose-derived stem cells in the repair and reconstruction of kidney and bladder is also increasing. OBJECTIVE:To summarize the adipose-derived stem cells research and its application in damage and repair of urinary system in recent years. METHODS:The first author retrieved PubMed database and CNKI databases for articles relevant to adipose-derived stem cells in the repair of urinary system published between January 2001 to September 2013 using the keywords of“adipose tissue-derived stem cel/adipose tissue-derived stromal cells/ADSCs;tissue engineering;kidney;ureter;ureathra;bladder;urology”in English and Chinese, respectively. Final y, 52 articles were included for further analysis. RESULTS AND CONCLUSION:Adipose-derived stem cells which can be found easily and have the unique advantages of multi-directional differentiation ability have been used for repairing and constructing the urinary system. Adipose-derived stem cells provide a new model of treatment for the urinary tract, which solves the traditional problems, including immune rejection, source of organs and ethical issues, and become an ideal cellsource in repair of urinary system. Accumulated data related to adipose-derived stem cells and its experiment and clinical application in repair of urinary system injuries have been reported. But before the cells are widely used in clinic, the fol owing problems need to be solved:its specific surface marker identification, specific conditions and control of celldifferentiation, mechanisms of action.