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Recently, programmed cell death 1(PD-1) inhibitors have shown a significant curative effect in the treatment of most solid cancers and some hematological malignancies. The effects of PD-1 inhibitors in recurrent head and neck squamous cell carcinoma (HNSCC) have also been confirmed. However, there is a lack of reliable clinical evidence to confirm the safety and efficacy of PD-1 inhibitors in patients after allogeneic hematopoietic stem cell transplantation, especially when the patient has a second primary cancer. Generally, graft-versus-host disease (GVHD) is unpredictable among these patients. Here we report the case of a patient who successfully used nivolumab without any GVHD or other immune-related adverse events for HNSCC after allogeneic bone marrow transplantation because of the Philadelphia chromosome-positive T cell acute lymphoblastic leukemia.

Objective Fluzoparib (SHR3162) is a novel, potent poly(ADP-ribose) polymerases (PARP)1, 2 inhibitor that showed anti-tumor activity in xenograft models. We conducted a phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial in patients with advanced solid cancer. Methods This was a 3+3 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China. Eligible patients for D-Esc had advanced solid tumors refractory to standard therapies, and D-Ex enrolled patients with ovarian cancer (OC). Fluzoparib was administered orally once or twice daily (bid) at 11 dose levels from 10 to 400 mg/d. Endpoints included dose-finding, safety, pharmacokinetics, and antitumor activity. Results Seventy-nine patients were enrolled from March, 2015 to January, 2018 [OC (47, 59.5%); breast cancer (BC) (16, 20.3%); colorectal cancer (8, 10.1%), other tumors (8, 10.1%)]; 48 patients were treated in the D-Esc arm and 31 in the D-Ex arm. The maximum tolerated dose (MTD) was 150 mg bid, with a half-life of 9.14 h. Grade 3/4 adverse events included anemia (7.6%) and neutropenia (5.1%). The objective response rate (ORR) was 30% (3/10) in patients with platinum-sensitive OC and 7.7% (1/13) in patients with BC. Among patients treated with fluzoparib ≥120 mg/d, median progression-free survival (mPFS) was 7.2 [95% confidence interval (95% CI), 1.8-9.3] months in OC, 9.3 (95% CI, 7.2-9.3) months in platinum-sensitive OC, and 3.5 (range, 2.0-28.0) months in BC. In patients with germline BC susceptibility gene mutation (gBRCA Mut) (11/43 OC; 2/16 BC), mPFS was 8.9 months for OC (range, 1.0-23.2; 95% CI, 1.0-16.8) and 14 and 28 months for BC (those two patients both also had somaticBRCA Mut). Conclusions The MTD of fluzoparib was 150 mg bid in advanced solid malignancies. Fluzoparib demonstrated single-agent antitumor activity in BC and OC, particularly in BRCA Mut and platinum-sensitive OC.

Breast cancer is the most common malignant tumor in Chinese women. Early screening is the best way to improve the rates of early diagnosis and survival of breast cancer patients. The peak onset age for breast cancer in Chinese women is considerably younger than those in European and American women. It is imperative to develop breast cancer screening guideline that is suitable for Chinese women. By summarizing the current evidence on breast cancer screening in Chinese women, and referring to the latest guidelines and consensus on breast cancer screening in Europe, the United States, and East Asia, the China Anti-Cancer Association and National Clinical Research Center for Cancer (Tianjin Medical University Cancer Institute and Hospital) have formulated population-based guideline for breast cancer screening in Chinese women. The guideline provides recommendations on breast cancer screening for Chinese women at average or high risk of breast cancer according to the following three aspects: age of screening, screening methods, and screening interval. This article provides more detailed information to support the recommendations in this guideline and to provide more direction for current breast cancer screening practices in China.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It is still unclear that the mechanisms by which long non-coding RNA (lncRNA) regulates tumorigenesis of TNBC. In this study, we explored the function and regulation of lncRNA in TNBC. Methods: The differentially expressed and overlapped lncRNAs were obtained from two microarray datasets of breast cancer. The Cancer Genome Atlas data was applied to validate the roles of top differentially expressed lncRNAs. The potential relationship among lncRNAs, miRNAs, and mRNAs and the effects of them on the TNBC tumorigenesis were further explored through multiple bioinformatic methods. Results: Long intergenic non-protein coding RNA 1351 (LINC01351) was first discovered to play an oncogenic role in TNBC. The highly expressed LINC01351 was significantly related to poor prognosis, aggressive subtypes, advanced stages and metastasis of breast cancer. LINC01351 was found to negatively regulate ELK4 which was involved in the transcriptional regulation in cancer. The high expression of ELK4 showed favorable prognosis of patients with basal-like 1 subtype and luminal androgen receptor subtype of TNBC.Conclusion: The dysregulation of LINC01351 played an important role in triple-negative breast cancer. LINC01351 could be a poor prognostic marker and a potential target for patients with TNBC.

S-1 is a multicomponent capsule containing tegafur, gimeracil, and oteracil potassium that has shown anticancer activity against numerous tumor types. However, S-1 capsules from different manufacturing companies have shown variations in pharmacokinetics and safety. Therefore, this multicenter, single-dose, randomized-sequence, open-label, two-way, self-crossover study was conducted to evaluate the bioequivalence of a newly developed generic S-1 (New Times Pharmaceutical Co., Ltd., Shandong, China) and the original brand-name S-1 capsule (Taiho Pharmaceutical Co., Ltd., Japan). Furthermore, the safety profiles of both products were compared. A total of 70 patients with 18 types cancer including breast, lung, gastric, and colorectal recruited at 5 hospitals who were randomly and alternatively administered 50 mg of the reference and test S-1 with a 7-day interval. Plasma concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), oteracil potassium, and 5-fluorouracil were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters, including maximum drug concentration (Cmax), time to achieve Cmax (Tmax), half-life (t1/2, area under the concentration-time curve from 0–time t (AUC0–t), and AUC from 0–infinity (AUC0–∞) were determined using non-compartmental analysis with DAS2.0 software. Bioequivalence of the reference and test S-1 was evaluated according to 90% confidence intervals (CIs) for ratios of AUC and Cmax of S-1. Adverse events were evaluated by monitoring symptoms, physical and laboratory examinations, electrocardiogram, and subject interviews. No significant difference was observed in plasma concentrations and pharmacokinetic profiles of tegafur, CDHP, oteracil potassium, or 5-fluorouracil (p > 0.05) among cancer patients treated with the reference or test S-1 formulation. The 90% CIs of Cmax, AUC0–t, and AUC0–∞ ratios were within the 80%–125% limit. The generic S-1 caused eight mild adverse events including liver dysfunction, diarrhea, nausea, fatigue, abnormal blood electrolytes, hyperglycemia, and dermal toxicity. Similarly, 18 mild adverse events were observed including dysarteriotony, diarrhea, nausea, fatigue, fever, hematotoxicity, abnormal blood electrolytes, hyperglycemia, dermal toxicity, and joint pain. There were no differences in the adverse event incidence between the two formulations. In conclusion, the newly developed generic S-1 showed similar pharmacokinetics to those of an original brand-name S-1 in cancer patients, thereby indicating bioequivalence. Furthermore, both treatments were well tolerated, suggesting that the cost-effective generic S-1 should be considered as a feasible option when treating patients.

Many biosimilars of monoclonal antibodies (mAbs) are becoming increasingly available as anticancer therapies, such as the rituximab, bevacizumab, and trastuzumab biosimilars. However, no comprehensive summary of their efficacy and safety is available. This study synthesized current evidence on the efficacy and safety of mAb biosimilars relative to their reference biologics among cancer patients. We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, the ISI Web of Science, and several Chinese databases from their inception dates to December 31, 2018, for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of biosimilars with reference biologics used in oncology. The binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs), continuous outcomes using weighted mean difference (WMD) with 95% CIs, and time-to-event outcomes using hazard ratios (HRs). Subgroup and sensitivity analyses were conducted following this. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the evidence. We did not find any comparative observational studies that fit the criteria. Twenty-three RCTs were identified for biosimilars of three mAbs, of which eight RCTs examined rituximab biosimilars (total N = 1534), six RCTs were for bevacizumab biosimilars (total N = 1897), and nine were for trastuzumab biosimilars (total N = 4953), respectively. The quality of the GRADE evidence for efficacy and safety outcomes was moderate or low. The findings were robust for all pre-specified subgroup and sensitivity analyses. The existing evidence suggests highly comparable efficacy and safety profiles between mAb biosimilars and their reference biologics in oncological drugs.

2044 Background: Management of advanced gliomas including glioblastoma multiforme (GBM) remains as an unmet medical need. Here we report our clinical experience with ACT001, or dimethylamino micheliolide, a synthesized derivative from parthenolide (a natural product of sesquiterpene lactone class), in Han Chinese patients with advanced glioma. Methods: Adult patients were enrolled in a 3+3 dose escalation phase 1 study with the following pre-defined ACT001 cohorts: 100mg, 200mg, 400mg, 600mg and 900mg, twice a day (BID). Pharmacokinetics and adverse events were evaluated during the study. Imaging studies were performed using RANO criteria to assess the therapeutic afficacy. Results: 16 patients with advanced glioma were enrolled in this single agent dose escalation study including 8 primary GBM, 4 astrocytoma (grade 2-3) and 4 other advanced glioma. The median age was 49 years (range: 31-70). Safety evaluation was performed in five cohorts and 13 of the 16 subjecst were evaluable for drug tolerability analysis. ACT001 was tolerated very well and no DLT or MTD was identified. Other than grade 1 adverse reactions (AE) in most cases and grade 2 AEs in other clinical findings, no drug-related grade 3 AE was noted. Pharmacokinetic analysis indicates that there was approximately linear correlate between the drug exposure (Cmax, AUC0-t and AUC0-inf) and study drug dosages evaluated. T1/2 is 4 hours with mean Cmax increased from approximate 300ng/ml to 5000ng/ml in a dose dependent manner with no significant dose accumulation during repeated dosing challenge. Post baseline MRI scans were performed in 11 out of 16 subjects. Among these 11 subjects, 1 GBM patient had a partial response (PR) at end of cycle 2 but had disease progressed at end of cycle 4; two non-GBM patients had a stable disease (SD) lasting for 5 or 6 cycles respectively before being taken off study due to disease pregression (PD) and other 8 patients had a PD. Of note, 9 out of these 11 subjects had stable or even improved clinical performance by the time they were taken off study due to PD. Five other subjects withdrew their consents or were taken off study due to clinical disease progression. Of note, subject S12 with diffusive astrocytoma was taken off study due to PD while still with a stable clinilcal performance and stereotactic biopsies targeting the progressed lesion didn’t reveal viable tumor tissues other than presence of macrophage/microglia. This subject was still alive 666 days after being taken off study. The mode of ACT001 actions is proposed to be at least partially related to its effects on tumor immune microenvironment. Conclusions: ACT001 was safe and tolerated well in patients. Clinical response was observed including a pathologic response in a subset of patients dosed at lower dose cohorts. iRANO criteria will be used in future studies based on its impacts on tumor immune microenvitonment. Clinical trial information: ChiCTR-OIC-17013604.

e15051 Background: Dysregulation of fibroblast growth factor receptor (FGFR) is strongly associated with establishment and progression of cancer. Pemigatinib is a selective FGFR1–3 inhibitor that are active in a targeted manner against cancers with activated FGFR pathway. The study was aimed at evaluating the tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) of pemigatinib in Chinese patients (pts) with advanced malignancy. Moreover, potential efficacy of pemigatinib was explored in a broad spectrum of FGFR alteration in variety of cancer types. Methods: In this phase 1 study, Chinese patients with advanced, recurrent or metastatic malignancy that were histologically or cytologically confirmed and harboring FGF/ FGFR 1-3 variation were enrolled. Pemigatinib was self-administered orally at 13.5 mg QD on a 3-week cycle (2-weeks-on/1-week-off schedule). Adverse events and other safety factors were monitored throughout the study. Blood samples were obtained at prespecified time points for PK and PD analysis and efficacy was assessed every 9 weeks per RECIST v1.1 guideline. Results: As of Jan 31, 2021, 12 patients with 5 different cancer types (colorectal cancer (4 pts), gastric and gastroesophageal junction carcinoma (3 pts), cholangiocarcinoma (2 pts), esophageal carcinoma (2 pts) and breast cancer (1pts)) were enrolled. Documented FGF/ FGFR1-3 alterations were FGFR amplification (6), FGFR point mutation (5), FGFR2 fusion (2) and FGF alteration (4) with 2 subjects had more than one alteration types. All the subjects were failed to at least 1 line of prior standard therapy. All patients had at least 1 treatment related adverse events (TRAE) and the most common ones were hyperphosphatemia (100%), decreased appetite (50%) and diarrhea (33.3%). Two patients (16.7%) reported ≥ grade 3 TRAEs, which were hyponatremia (8.3%) and proteinuria (8.3%). There were no TEAEs leading to death or treatment discontinuation. Among 11 efficacy evaluable patients, 2 of them had partial responses (PR) as evaluated by investigators with 1 cholagiocarcinoma harboring FGFR2 point mutation (p.F276C) and the other esophageal carcinoma carrying FGFR1 mutation (p.A354V). 3 patients had a best overall response of stable disease (SD). The objective response rate (ORR) was 16.7% (95%CI: 2–48%) and disease control rate was 41.7% (95%CI: 15–72%). Conclusions: Pemigatinib had an acceptable and manageable toxicity and demonstrated a possible anti-cancer benefit in Chinese patients with advanced malignancy that accompanied with FGF/FGFR1-3 aberrance. A significant implication of the data is that it extended the population that potentially benefit from pemigatinib other than FGFR2 fusion/rearrangement. Clinical trial information: NCT04258527.

e12569 Background: Breast cancer (BC) is one of the most common malignant tumors among women in the world. Although under 7% of all BC cases, young BC is more difficult to diagnose and can be aggressive and less likely to respond to treatment. Exploring and identifying potential biomarkers for the diagnosis and prognosis of younger BC patients is necessary. Methods: A total of 1,202 BC patients under 35 years old (YD) were enrolled. Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Statistical analysis was performed by Fisher’s exact test. Results: Of 1,202 young BC patients, 3 were under 20 YD, 85 were 20-25 YD, 371 were 26-30 YD, and 747 were 31-35 YD. Based on pathological, there were 899 infiltrative duct carcinomas, 10 infiltrative lobular carcinomas, and 292 BCs with unclear pathological type. According to molecular features, 587 HR+/HER2- (group I), 118 HR+/HER2+ (group II), 75 HR-/HER2+ (group III) and 193 HR-/HER2- (group IV) were included. Chemotherapy, radiotherapy, endocrine therapy and targeted therapy were received and 1074 patients were followed up. The median overall survival (OS) was 76 (5-156) months. There was no significant difference in OS between different treatments. The median OS was 81 (range 5-156) months, 67 (range 10-153) months, 76 (range 14-146) months, and 78 (range 13-151) months for group I, II, III, and IV, respectively. The significantly lower OS was observed in group II ( P=0.044). Although group II and group III had similar proportion of targeted treatment (43.22% vs 43.24%, respectively), the OS rate was different (67 vs 76 months, P=0.064). Samples from 46 young BC patients were performed on deep sequencing targeting 450 cancer genes. The most common mutations were TP53 (56%), GATA3 (29%), ERBB2 (27%), CDK12 (20%), and FGFR1 (20%). Different from previous studies, only 4.35% (2/46) of BRCA1/2 mutations were detected in this cohort. The mutation frequency of GATA3 in group II was significantly lower than that in group III (0% vs 71.43%, P=0.017). Conclusions: The most common pathological type of young BC was infiltrative duct carcinoma. The OS of HR+/HER2+ patients were significantly lower than that of others. Our results showed that GATA3 could be a potential biomarker for OS prediction for BC with HER2+, which help to further guide targeted therapy in young BC patients.

Apatinib (YN968D1) is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a single-arm, nonrandomized phase II study (NCT03121846) to assess the efficacy and safety of apatinib in patients with stage IV sarcoma. We recruited 64 patients with stage IV sarcoma who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were evaluated. Fifty-nine patients were assessed for efficacy and 64 patients for AEs. The median PFS was 7.93 months. At 12 weeks, the PFR was 74%, the ORR was 16.95% (10/59), and the DCR was 86.44% (51/59). The final ORR was 15.25% (9/59) and the DCR was 57.63% (34/59). Notably, 22 patients (34.38%) who developed hypertension, hand-foot-skin reaction, or proteinuria had significantly longer OS than those without these AEs (18.20 vs. 10.73 months; P = 0.002). We conclude that apatinib is effective and well tolerated in patients with advanced sarcoma. The development of hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in sarcoma patients., Cancer: Starving sarcomas into submission A drug that inhibits blood vessel growth offers a potentially promising treatment for a class of tumors with a poor prognosis. Sarcomas form in bone and connective tissue, and patients with advanced disease have a five-year survival rate of less than 10%. Researchers led by Jilong Yang of the Tainjin Medical University Cancer Institute & Hospital in China tested apatanib, a drug that starves tumors by preventing blood vessel development, in late-stage sarcoma patients. Strikingly, 15% of the patients experienced tumor reduction after treatment, and more than half overall achieved at least partial disease control. Adverse events were generally mild, but Yang and colleagues observed that patients who experienced certain side-effects achieved a greater survival benefit from treatment. These results support further investigation of this drug, and offer hints of possible biomarkers to predict response.

Background: To compare survival and side-effects between patients with metastatic breast cancer (MBC) treated with paclitaxel/carboplatin (TP) or paclitaxel/epirubicin (TE) chemotherapy. Patients and methods: From June 2009 to April 2012, 121patients were randomly assigned, 61 of whom were randomized to TP and 60 to TE. Baseline characteristics were relatively well-balanced in the two treatment arms. Table 1 Baseline patient characteristicsCharacteristicTP(n=61)TE(n=60)P(χ2 test)Median age,years(range)53.5(35-68)51.8(32-69)0.614ECOG performance status Results: After a median follow-up of 21.3 months, there was no significant difference between the two treatment arms in objective response rate(ORR) (68.5 % vs. 73.3%, respectively;). And both the progression-free survival (P=0.704)and overall survival (P=0.403)were very similar between the two arms. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions and alopecia. There was more grades 3–4 alopecia and more nausea with TE(p Table 2 Summary of adverse events per patient; p-values are given overallTP (n=61)TE (n=60)P valueAdverse eventsGrades 1-4Grades 3-4Grades 1-4Grades 3-4Neutropenia46133870.149Leukopenis50114070.054Anemia40410.981Thrombocytopenia41300.714Lymphocytopenia20410.391Vomiting1532060.289Nausea2724150.010Diarrhea40300.714Alopecia441560310.000Cardiotoxicity30600.523Hypersensitivity reaction0000-ALT increase50700.523Peripheral neurotoxicity2001900.895Overall p value for the comparison of grades 1-4 are given Conclusion: This study did not found significant differences in ORR, PFS and OS between TP and TE arms. Both arms were well tolerated. TP has some advantages in less side-effects, especially alopecia and nausea.This combination can be safely prescribed to patients in which anthracyclines have the potential of being harmful such as those previously exposed to anthracyclines in the adjuvant setting. Citation Format: Zhongsheng Tong, Shufen Li, Yehui Shi, Xu Wang, Chunfang Hao, Lihong He, Guolei Dong, Xiaorui Wang, Yongsheng Jia, Li Zhang. Phase III trial evaluating paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-10-05.

A postmenopausal patient with a diagnosis of estrogen receptor (ER) (+), progesterone receptor (PR) (+), and human epidermal growth factor receptor-2 (HER2) (-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient’s tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases (PI3K) signaling pathway were detected via next-generation sequencing (NGS)-based liquid biopsy, including a p. G1007R missense mutation in exon 21 of PIK3CA (33.61%), a p.L70fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten (PTEN) (49.14%), and a p. D1542Y missense mutation in exon 32 of mammalian target of rapamycin (mTOR) (1.66%). Therefore, only the mTOR inhibitor everolimus was administered to the patient. Partial remission (PR) was observed after 2 months, and sustained stable disease (SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3CA decreased to 4.17%, and that the PTEN and mTOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3K/ARK/mTOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.

Yongsheng Jia,1,* Chunze Zhang,2,* Liyan Zhou,1,* Huijun Xu,3 Yehui Shi,1 Zhongsheng Tong1 1Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Colorectal Surgery, Tianjin Union Medicine Center, Tianjin, People’s Republic of China; 3Department of Oncology, Anhui Provincial Tumor Hospital, Hefei, People’s Republic ofChina *These authors contributed equally tothis work Abstract: Micheliolide (MCL) is a promising novel compound with broad-spectrum anticancer activity. However, little is known regarding its action and mechanism in breast cancer. To explore the potential therapeutic application of MCL as a chemosensitivity modulator, this study investigated the effects of MCL on cisplatin sensitivity in breast cancer and the underlying mechanisms. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay and a xenograft tumor model, MCL enhanced the cisplatin sensitivity of the breast cancer cell line MCF-7 both in vitro and in vivo. Treatment of MCF-7 cells with low-dose cisplatin (10 µM) was sufficient to enrich the proportion of ALDH+ cells and upregulate Krüppel-like factor 4 (KLF4) expression. The results obtained from knockdown and overexpression experiments demonstrate that KLF4 is both necessary and sufficient to induce a cisplatin resistance phenotype in breast cancer cells. Furthermore, the glutathione (GSH) content was elevated in MCF-7 cells after overexpression of KLF4. KLF4-mediated resistance to cisplatin was found to be abrogated by treatment with buthionine sulfoximine, an inhibitor of GSH synthesis. MCL induced GSH depletion and severe cell death in KLF4-overexpressing MCF-7 cells following exposure to cisplatin. Therefore, these results suggest that MCL-mediated direct depletion of GSH represents a major mechanism in reversing KLF4-induced cisplatin resistance in MCF-7 cells. Keywords: KLF4, cisplatin resistance, glutathione, breast cancer, Micheliolide

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

Objective: The objective of the study was to compare disease-free survival and overall survival in a group of matched males and females with breast cancer, and to analyze possible treatment- and gender-related differences. Methods: We retrospectively analyzed the data of 150 operable male breast cancer patients treated in our hospital from December 1980 to June 2012. Each male breast cancer patient recorded in the database was matched with two female breast cancer patients of equal stage. Prognosis in terms of disease-free survival and overall survival was evaluated. Results: The mean age at diagnosis was 58.6+9.7 years for males and 57.2+10.3 years for females. The median follow-up was 69 months for males and 81 months for females. Significant differences were identified for tumor location, hormone receptor status, molecular subtypes and hormone therapy between the two groups. Monofactorial analysis demonstrated that tumor size, lymph node state, American Joint Committee on Cancer stage, molecular subtypes and adjuvant chemotherapy treatment were prognostic factors in male breast cancer patients. The 5- and 10-year disease-free survival rates were 65.6 and 40.1% for males, and 74.9 and 51.5% for females, respectively. The 5- and 10-year overall survival rates were 72.9 and 53.9% for males, and 83.2 and 68.5% for females, respectively. There was significantly difference in disease-free survival and overall survival between the two matched groups (P ¼ 0.002). Conclusions: Male breast cancer patients had inferior outcome despite of equal stage in comparison with matched female breast cancer patients, which demonstrates that biological differences may contribute to the worse prognosis.

This study aimed at analyzing the therapeutic function of the chemokine RANTES on the H22 hepatoma ascites model and preliminarily explore the mechanism of RANTES in malignant ascites to provide an important reference for applying chemokines in anti-tumor therapy. The murine H22 hepatoma ascites model was used. Three treatment groups were analyzed: a RANTES treatment group, an IL-2 control group, and an NS control group. Two regimens of early treatment and late treatment were designed, and the therapeutic effect of RANTES on malignant ascites was studied by measuring changes in mouse body weight and abdominal circumference and observing the survival time. The expression of TNF-α, IFN-γ, TGF-β1, and MCP-1 in mouse ascites was detected by ELISA, and the chemotactic function of RANTES on B lymphocytes and T lymphocytes was analyzed by flow cytometry. In the early and late treatment regimens, RANTES could effectively inhibit the increase in mouse body weight and abdominal circumference in the murine H22 hepatoma ascites model. The secretion of TNF-α and IFN-γ, which had anti-tumor effects, was higher in the RANTES treatment group than in the control groups (P

Objectives: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. Methods: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were ââpemetrexedââ or ââLY231514ââ or âAlimtaâ, âmetastatic breast cancerâ, and âadvanced breast cancerâ. Results: There were 15 studies (n = 1002) meeting our criteria for evaluation. Eight single-agent trials (n = 551) and seven using combinations with other agents (n = 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. Conclusion: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists. Keywords: Metastatic breast cancer, Chemotherapy, Pemetrexed, Anthracycline, Taxane