Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Overcoming resistance to endocrine therapy in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR / 医学前沿

New targeted therapies have been developed to overcome resistance to endocrine therapy (ET) and improve the outcome of HR

Progress in systemic therapy for triple-negative breast cancer / 医学前沿

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a heterogeneous genetic profile. Chemotherapy exhibits substantial activity in a small subset of these patients. Drug resistance is inevitable. Major progress has been made in the genetic analysis of TNBC to identify novel targets and increase the precision of therapeutic intervention. Such progress has translated into major advances in treatment strategies, including modified chemotherapy approaches, immune checkpoint inhibitors, and targeted therapeutic drugs. All of these strategies have been evaluated in clinical trials. Nevertheless, patient selection remains a considerable challenge in clinical practice.

Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease / 中华肿瘤杂志

The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.

Progress on clinical trials of cancer drugs in China, 2019 / 中华肿瘤杂志

Objective@#To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019.@*Methods@#The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted.@*Results@#There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019.@*Conclusions@#Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.

The clinical reports on adrenal insufficiency of patients with advanced solid tumors accepting anti-PD-1 antibody, SHR-1210 therapy / 中华肿瘤杂志

Objective@#To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy.@*Methods@#The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency.@*Results@#Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210.@*Conclusions@#The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.

Feasibility and toxicity of EC-T dose-dense adjuvant chemotherapy: A real world study in Chinese early-stage breast cancer patients with high recurrence risk / 中华肿瘤杂志

Objective@#We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk.@*Methods@#370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed.@*Results@#370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282).@*Conclusions@#EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Genetic variation in DNA polymerase kappa gene is associated with the prognosis after platinum-based chemotherapy in small cell lung cancer patients / 中华肿瘤杂志

Objective@#To investigate the associations between genetic variations of DNA polymerase kappa (POLK) and treatment response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival.@*Methods@#Five haplotype-tagging single nucleotide polymorphisms (htSNPs) of POLK were genotyped by Sequenom MassARRAY methods in 1 030 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between SNPs and treatment response were analyzed by computing the odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios (HRs) and 95% CIs.@*Results@#Among 1 030 cases, 558 (54.2%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Seven hundred and eighty eight patients were chemotherapy responders in the study with a response rate of 76.5%. The median follow-up time of these patients was 22.0 months. Patients were followed up to get their survival information. The median survival time of these patients was 22.5 months. Six hundred and seventy three patients (65.3%) had died by the last date of follow-up to get their survival information (Dec 21, 2017). Five htSNPs of POLK were not associated with the chemotherapy response of SCLC patients who received platinum-based chemotherapy (all P>0.05). Multivariate Cox proportional hazards regression model analysis showed that, rs73120833 of POLK was significantly associated with the overall survival (OS) of SCLC patients, compared with POLK rs73120833 T allele, C allele can prolong OS (adjusted HR=0.87, 95% CI=0.77-0.97, P=0.021). The remaining 4 SNPS, including rs10077427, rs3756558, rs4549504 and rs5744545, were not significantly associated with overall survival. Age≤56, KPS> 80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (all P<0.05).@*Conclusion@#These results suggest that POLK genetic polymorphism rs73120833 plays an important role on the prognosis of SCLC patients, which can be potential genetic biomarker for SCLC personalized treatment.

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.

Comprehensive management guideline for breast cancer follow-up and concomitant diseases / 中华肿瘤杂志

In recent years, with the emphasis on breast cancer screening and the improvement of breast cancer diagnosis and treatment, five-year survival rate and the overall survival time of breast cancer patients have been significantly improved in China. The adverse events caused by patients′ age, changes in hormone levels or anti-cancer treatment during follow-up have become new challenges in the management of patients with breast cancer, not only affecting the quality of life, but also impacting disease recurrence and death. The management of patients should not be restricted to the diagnosis and treatment of breast cancer, but to a most comprehensive management. This could improve the therapeutic efficacy of anti-cancer treatment and the quality of life of patients. Based on the current landscape of treatment and follow-up of breast cancer patients in China, the experts committee drafted the "Comprehensive Management Guideline for Breast Cancer Follow-up and Concomitant Diseases" according to the literature and relevant guidelines. This guideline is composed of four parts: path diagram, follow-up management, concomitant diseases and adverse events management. It aims to standardize the long-term follow-up of breast cancer patients, guide clinicians to deal with the concomitant diseases and adverse events, and further improve the prognosis and quality of life of breast cancer patients in China.

Profile of gene mutations and targeted treatment of brain metastases in breast cancer / 国际肿瘤学杂志

Brain metastasis (BM) is considered one of the major causes of mortality in breast cancer patients.BM develops more frequently in triple-negative breast cancer and human epidermal growth factor receptor 2 (HER2)-positive breast cancers,while the incidence of BM in hormone receptor positive is much lower.Mutations and expression of BM of breast cancer are differ from their primay tumors.Importantly,some therapeutic actionable mutations can be present in the BM while not in the primary tumors.Current targeted therapeutics in BM of breast cancers are limited,and drugs used have proven effects on the primary tumors but lack specificity for the BM.The identification of genomic and expressional alterations specific to BM are crucial to the development of BM specific targeted therapies.

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.

Clinical observation of thyroid-related adverse events induced by anti-PD-1 antibody SHR-1210 in patients with advanced solid tumor / 中华肿瘤杂志

Objective@#To assess the incidence and characteristics of thyroid dysfunction during anti-Programmed cell death 1 receptor (PD-1) antibody SHR-1210 therapy in patients with advanced solid tumor.@*Methods@#The medical records of 98 patients who initiated SHR-1210 treatment between April 27, 2016 and June 8, 2017 in the phase 1 trial to evaluate the safety, efficacy, and pharmacokinetics of SHR-1210 in patients with advanced solid tumors were retrospectively reviewed. Serological tests of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at baseline and prior to each SHR-1210 administration.@*Results@#A total of 86 patients had normal thyroid function before the first dose of SHR-1210 treatment. Nine out of 86 (10.5%) patients developed new onset hypothyroidism from euthyroid state. 12 patients presented thyroid dysfunction at baseline, 10 of whom were subclinical hypothyroid and 2 were hypothyroidism. Four out of 10 patients developed hypothyroidism from subclinical hypothyroid. Most patients with hypothyroidism were asymptomatic. Thyroid dysfunction occurred early (median, 55days) after the initiation of SHR-1210. The severity of hypothyroidism were all grade 1-2. No grade 3-4 hypothyroidism occurred. No patients discontinue the treatment of SHR-1210 due to clinical impact of the thyroid dysfunctions.@*Conclusions@#Thyroid-related adverse events were common during anti-PD-1 antibody SHR-1210 treatment . The incidence of hypothyroidism is lower in patients with euthyroid state than in patients with thyroid dysfunction at baseline during SHR-1210 treatment . Thyroid function can be improved after thyroid hormone replacement. During SHR-1210 treatment, it is necessary to pay attention to monitor the thyroid function, especially in the patients with thyroid dysfunction at baseline.@*Trial registration@#Chinese Clinical Trial Registry, 2016L01455

Clinical outcome of receptor expression discordance between primary and metastatic breast cancer / 中华肿瘤杂志

Objective@#To investigate the clinical outcome of expression discordance of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) in primary breast cancer and the corresponding metastatic lesions.@*Methods@#A retrospective analysis was performed on 178 breast cancer patients with metastasis confirmed by the National Cancer Center & Cancer Hospital, Chinese Academy of Medical Sciences in the past 6 years. The data of expressions of ER, PR and HER-2 in primary and metastatic breast cancer, the metastatic sites, disease progression were collected and the relationships of the expression discordance of receptors with prognosis were analyzed.@*Results@#The discordance rates of ER, PR and HER-2 between the primary tumor and the metastatic sites were 27.0%, 39.8% and 18.7%, respectively. The discordance rates of ER, PR and HER-2 of patients with locoregional recurrence were 21.9%, 36.6% and 12.7%, respectively, while those of patients with distant metastases were 31.3%, 42.7% and 23.8%. The median progression free survivals (PFS) of ER+/+、ER+/-、ER-/+、ER-/- of primary tumor and metastatic sites were 17.7 months, 10.3 months, 14.0 months and 9.0months, respectively (P=0.025). The median PFS of PR+/+, PR+/-, PR-/+, PR-/- were 23.0 months, 10.7 months, 14.0 months and 9.2months, respectively (P=0.002). The median PFS of HER-2+/+, HER-2+/-, HER-2-/+, HER-2-/- were 14.9 months, 15.2 months, 12.3 months and 14.0 months, respectively, without significant differences (P=0.588).@*Conclusions@#This study confirms that expression discordances of ER, PR and HER-2 between primary breast cancer and the corresponding metastatic lesions are dramatic, especially in the patients with distant metastasis. The unstable levels of ER and PR seem to be significantly associated with prognosis of breast patients.

Clinical value of heat shock protein-90α on diagnosis, prediction of treatment response, and monitoring of relapse in breast cancer / 中国肿瘤临床

To explore the prognostic value of heat shock protein-90α (HSP-90α) plasma levels on breast cancer and non-breast malignant tumors, monitoring the response of chemotherapy, and the predictive value of cancer recurrence and metastasis. Methods: A total of 615 female patients were enrolled between June 2016 and September 2016 in Cancer Hospital, Chinese Academy of Medical Sciences, who were divided into the examination (n=389) and control (n=216) groups. The former group consisted of static (n=289) and dynamic (n=110) groups, which were analyzed by stages, histological and molecular type, and so on. The latter group in-cluded healthy people (n=103), and those with breast benign tumors (n=51) and non-breast malignant tumors (n=62). In all the plasma samples, HSP-90α was detected using a double-antibody enzyme-linked immunosorbent assay. The receiving-operating characteristic curve was used to analyze the effectiveness of plasma HSP-90α in the diagnosis of breast cancer. Wilcoxon＇s rank test and the Kruskal-Wallis test were used to analyze the association between clinical characteristics and levels of plasma HSP-90α. Results: The levels of plasma HSP-90α were significantly higher in patients with breast cancer than in healthy controls (P<0.001). When the cut-off value was set as 59.7 ng/mL for the diagnosis of breast cancer and 43.22 ng/mL for disease recurrence, the areas under the curve were 0.834 and 0.877, sensitivities were 90.3% and 95.7%, and specificities were 78.6% and 74.5%, respectively. The levels of plasma HSP-90α sig-nificantly decreased after achieving a response to neoadjuvant chemotherapy or surgery (P<0.05). Conclusions: Plasma HSP-90α has good clinical value in the diagnosis and monitoring of response and recurrence in breast cancer.

Genetic polymorphisms of autophagy-related gene 5 (ATG5) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy / 癌症

BACKGROUND@#Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy.@*METHODS@#We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom's MassARRAY system. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.@*RESULTS@#Three genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence (P = 0.024). Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 (P = 0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04-2.87; P = 0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele (P = 0.027).@*CONCLUSION@#ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.

The treatment and prognosis of peripheral primitive neuroectodermal tumor / 中华肿瘤杂志

Objective@#To evaluate the treatment and prognosis of peripheral primitive neuroectodermal tumor (pPNET).@*Methods@#From March 2006 to April 2015, 47 patients with pPNET who had undergone chemotherapy in our hospital were enrolled. The clinical data and survival information of these patients were collected and interpreted retrospectively to analyze the effect of each treatment on the survival of patients.@*Results@#The median overall survival (OS) for whole group was 23.5 months, and 5-year survival rate was 33.8%. In the patients who underwent radical surgery, the median OS was 70.4 months, the 5-year survival rate was 54.4%, the median disease-free survival (DFS) was 23.1months, and 5-year DFS rate was 34.4%. Sixteen patients had recurrences or metastasis after surgery. Eighty-one percent of them (13/16) occurred within 2 years after surgery. The difference of median OS between patients who got adjuvant chemotherapy and those who did not was statistically significant (P=0.04). But the difference of median PFS between these two groups was not statistically significant (P=0.057). There was no statistically significant difference for median OS (P=0.619) and median DFS (P=0.191) between patients who got adjuvant radiotherapy and those who did not. The recurrence rate between these two groups was not statistically significant (P=0.40). The median OS and PFS for 34 patients who received first-line palliative chemotherapy was 10.7 months and 3.2 months. 1-year and 2-year survival rates were 48.0% and 17.8%. The response rate and clinical benefit rate for first-line chemotherapy was 53.1% and 75.0%. The median PFS and OS for patients who received platinum-based regimens were 3.3 months and 14.5 months. The median PFS and OS for patients who got non-platinum regimens were 2.7 months and 10.3 months. There was no significant difference of PFS and OS between platinum-based and non-platinum regimens. Palliative surgery and radiotherapy did not improve the OS of pPNET this cohort.@*Conclusions@#Comprehensive treatment including chemotherapy, radiotherapy and surgery is the standard treatment model for early pPNET patients. Adjuvant chemotherapy significantly improved the overall survival of early pPNET patients. Chemotherapy is the main treatment for patients with advanced pPNET. Platinum-based chemotherapy seem to be a good option.

Correlations between genetic variations of glutathione synthetase gene and the response to platinum-based chemotherapy and prognosis of small cell lung cancer patients / 中华肿瘤杂志

Objective@#To explore the associations between genetic variations of glutathione synthetase gene (GSS) and response to platinum-based chemotherapy of small cell lung cancer(SCLC), and to analyze the influencing factors on survival.@*Methods@#Four haplotype-tagging single nucleotide polymorphisms (htSNPs) of GSS were genotyped by Sequenom MassARRAY methods in 903 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were measured by odds ratios (OR) and 95% confidence intervals (CI), adjusted for sex, age, smoking, KPS, staging and chemotherapy regiments, by unconditional logistic regression model. The hazard ratios (HR) were estimated by Cox proportional hazards regression model.@*Results@#Among the 903 patients, 462(51.2%) cases received cis-platinum and etoposide treatment while others were treated with carboplatin and etoposide. 656 patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time (MST) of these patients was 25.0 months.We found that rs725521 located in the 3′ near gene region of GSS was significantly associated with chemotherapy response. Compared with the T allele, patients with C allele had a worse chemotherapy response and an increased risk of no-responders (P=0.027). Rs7265992 and rs725521 of GSS were associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy (HR=1.16, 95% CI=1.02-1.33, P=0.027; HR=1.17, 95% CI=1.05-1.31, P=0.006, respectively). The patients carrying 1 or 2 risk alleles and the patients carrying 3 or 4 risk alleles had worse MST than the patients without the rs7265992A and rs725521C risk alleles (24.0 and 22.0 versus 30.0 months), with the HR for death being 1.26 (95% CI=1.04-1.54) and with the HR of 1.52 (95%CI=1.18-1.97, P=0.001). Rs2025096 and rs2273684 were not associated with the OS of SCLC patients who received platinum-based chemotherapy. Age ≤ 56, KPS> 80, limited-stage, chemotherapy response and radiation therapy had a remarkably prolonged OS (all P<0.05).@*Conclusions@#These results suggest that GSS genetic polymorphism rs725521 plays an important role in the response to platinum-based chemotherapy, while rs7265992 and rs725521 have important effect on the prognosis of SCLC patients, which may be potential genetic biomarkers for personalized treatment of SCLC.

Clinical progress and future of targeted therapy for breast cancer / 中国肿瘤临床

Targeted therapy is one of the most important treatments for breast cancer. In recent years, an increasing number of target-ed therapeutic drugs have been developed for different subtypes of breast cancer. The clinical application of these drugs has greatly improved the efficacy and changed the clinical practice for breast cancer. Overcoming drug resistance and developing new drugs that can go beyond the efficacy of traditional targeted drugs are two of the most important research directions in the future.

Advances of fulvestrant in treatment of advanced breast cancer in hormone receptor-positive postmenopausal women / 中国癌症杂志

Endocrine therapy targeting estrogen pathway is one of the ifrst-line treatment choices of advanced breast cancer. Fulvestrant is a pure estrogen antagonist that blocks and downgrades estrogen receptor, which makes it effective in the treatment of progression after prior endocrine therapy. Fulvestrant 250 mg per month regime was approved for postmenopausal women with hormone-positive advanced breast cancer after progression or recurrence on antiestrogen therapy. Fulvestrant 500 mg per month regime was approved by the EMA and the US FDA in the same population based on the CONFIRM trial which proved improved efifcacy and similar tolerance compared with 250 mg regime. Recent trials were focused in the ifrst-line treatment and combination use with other therapeutics. This review discusses the advances of fulvestrant in postmenopausal women with hormone-positive advanced breast cancer.