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.

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.

The landscape of palliative systemic therapy and overall survival analysis of elderly patients with advanced breast cancer in China National Cancer Center / 国际肿瘤学杂志

Objective To compare the survival data of elderly advanced breast cancer (ABC)patients in China National Cancer Center with USA and summarize the therapeutic characteristics in elderly ABC patients via real world study. Methods We summarized the clinicopathological characteristics,therapeutic regimens and survival outcome of 1425 females with ABC who were initially hospitalized between January 2003 and De-cember 2013 from Database in China National Cancer Center and compared with 21185 ABC patients in the Surveillance,Epidemiology,and End Results (SEER)database. Results The median overall survival (OS) of elderly patients was significantly shorter than that of the young group in China National Cancer Center (35. 5 months vs. 43. 9 months;χ2 = 8. 747,P = 0. 003),which was similar to the survival feature in SEER database (24. 0 months vs. 36. 0 months;χ2 = 540. 227,P < 0. 001). Compared with the young population, significantly more elderly patients suffered from the medical complications of hypertension [30. 3％ (67 / 221) vs. 9. 5％ (114 / 1204);χ2 = 73. 073,P < 0. 001],diabetes [14. 5％ (32 / 221)vs. 4. 7％ (57 / 1204);χ2 = 30. 220,P < 0. 001]and heart disease [6. 3％ (14 / 221)vs. 1. 7％ (20 / 1204);χ2 = 17. 638,P <0. 001]. In estrogen receptor (ER)and/ or progesterone receptor (PR)-positive patients,the percentage of re-ceiving first-line endocrine therapy in elderly patients was significantly larger than that of the young population [26. 9％ (43 / 160)vs. 9. 5％ (80 / 841);χ2 = 37. 599,P < 0. 001]. Moreover,in ER and/ or PR-positive population,the elderly patients underwent first-line endocrine therapy resulted in better OS than those under-went first-line chemotherapy (49. 9 months vs. 32. 6 months;χ2 = 4. 774,P = 0. 029),while no significant difference was observed between these two therapeutic modes in the young population (56. 9 months vs. 48. 8 months;χ2 = 1. 103,P = 0. 294). Conclusion The proportion of elderly ABC patients with the medical complication of hypertension,diabetes and heart disease is significantly larger than that of the young population, which may lead to the difference in treatment decision making. In ER and/ or PR-positive elderly ABC patients, receiving first-line endocrine therapy may result in better survival than first-line chemotherapy.

The landscape of palliative systemic therapy and overall survival analysis of elderly patients with advanced breast cancer in China National Cancer Center / 国际肿瘤学杂志

Objective@#To compare the survival data of elderly advanced breast cancer (ABC) patients in China National Cancer Center with USA and summarize the therapeutic characteristics in elderly ABC patients via real world study.@*Methods@#We summarized the clinicopathological characteristics, therapeutic regimens and survival outcome of 1 425 females with ABC who were initially hospitalized between January 2003 and December 2013 from Database in China National Cancer Center and compared with 21 185 ABC patients in the Surveillance, Epidemiology, and End@*Results@#(SEER) database. Results The median overall survival (OS) of elderly patients was significantly shorter than that of the young group in China National Cancer Center (35.5 months vs. 43.9 months; χ2=8.747, P=0.003), which was similar to the survival feature in SEER database (24.0 months vs. 36.0 months; χ2=540.227, P<0.001). Compared with the young population, significantly more elderly patients suffered from the medical complications of hypertension [30.3% (67/221) vs. 9.5% (114/1 204); χ2=73.073, P<0.001], diabetes [14.5% (32/221) vs. 4.7% (57/1 204); χ2=30.220, P<0.001] and heart disease [6.3% (14/221) vs. 1.7% (20/1 204); χ2=17.638, P<0.001]. In estrogen receptor (ER) and/or progesterone receptor (PR)-positive patients, the percentage of receiving first-line endocrine therapy in elderly patients was significantly larger than that of the young population [26.9% (43/160) vs. 9.5% (80/841); χ2=37.599, P<0.001]. Moreover, in ER and/or PR-positive population, the elderly patients underwent first-line endocrine therapy resulted in better OS than those underwent first-line chemotherapy (49.9 months vs. 32.6 months; χ2=4.774, P=0.029), while no significant difference was observed between these two therapeutic modes in the young population (56.9 months vs. 48.8 months; χ2=1.103, P=0.294).@*Conclusion@#The proportion of elderly ABC patients with the medical complication of hypertension, diabetes and heart disease is significantly larger than that of the young population, which may lead to the difference in treatment decision making. In ER and/or PR-positive elderly ABC patients, receiving first-line endocrine therapy may result in better survival than first-line chemotherapy.

The application of circulating tumor cells in the diagnosis and treatment of breast cancer / 国际肿瘤学杂志

In recent years,the clinical utility of circulating tumor cells (CTCs)analysis from peripheral blood has undoubtedly become a popular topic in the field of precision medicine.CTCs analysis is a noninvasive,easily obtained and highly repeatable testing approach,and could be carried out in a real-time manner,which has never failed to surprise us with great progression in the detection of early disease,assessing prognosis,treatment response monitoring and individualized therapeutic direction in breast cancer.