Systemic chemotherapy for metastatic breast cancer

Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer （MBC）. Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metasta- sis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combi- nation agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel- bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and catuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall sur- vival with maintenance chemotherapy according to a Korean phase III clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy （X-based X） appears favorable based on a series of domestic studies.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

Efficiency and safety of trastuzumab plus chemotherapy in Her-2 overexpressing metastatic breast cancer patients

Objective： The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer （MBC） patients. The primary endpoint was overall response rate （ORR） and the second endpoint was clinical benefit rate （CBR） and toxcities. Methods： Estrogen recep- tor （ER） （-）, progesterone receptor （PR） （-）, Her-2 （＋＋＋） patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group （H group） and 75 of them were assigned to the Control group （C group）. They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results： Response rate （RR） of the H group and the C group were 51.0% and 24.0% separately, and the difference were statistically significant （P 〈 0.05）. CBR of the two groups were 76.4% （H group） and 64.0% （C group）, had significant difference （P 〈 0.05）. Complete response rate （CRR） of the two groups were 21.5% and 6.6%, there were no significant difference between the two groups （P = 0.055）. Grade 3-4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy （17.6%） and 4 patients with chemotherapy （5.4%）, with no statistical significance （P = 0.054）. In the subgroup of antharcycline-containing regimens, Grade 1-4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracyciine contained chemotherapy （H ＋ ACCT arm; 40.9%, g/22）], and 4 patients in the antharcycline- containing chemotherapy arm （ACCT arm; 12.5%, 4/32）. There was statistical significant difference between the two arms （P 〈 0.05）. Grade 3--4 cardiac toxicity, the occurance rates were 18.1% （4/22） in H ＋ ACCT arm and 6.3% （2/32） in ACCT arm, and there was no significant statistical difference （P = 0.352）. Grade 3-4 granulocytopenia in the H group and C group were 27.5% （14/51） and 26.7% （20/75）, with no significant difference （P = 0.922）. Conclusion： The efficiency of trastuzumab combining with chemotherapy using as first line regimen in Her-2 overexpressing MBC patients were exact. However, the long-term cardiac toxicity can be hidden troubles of trastuzumab using.

Treatment patterns for adjuvant docetaxel-based chemotherapy in early-stage breast cancer in China：A pooled retrospective analysis of four observational studies

Objective：Adjuvant docetaxel-based chemotherapy is frequently used for operable early breast cancer（EBC）.This study investigated patterns of use of docetaxel（T）in real-life clinical practice in China.Methods：This was a retrospective pooled analysis of the Asia-Pacific Breast Initiatives（APBI）Ⅰ（2006–2008）and Ⅱ（2009–2011）registries,and two Chinese observational studies;BC STATE（2011–2014）and BC Local Registry（2007–2010）.Female Chinese adults（≥18 years）with operable breast cancer treated with docetaxel-based adjuvant chemotherapy were included in the analysis.Patients with metastatic disease were excluded.The primary endpoint was assessment of treatment patterns and patient profiles.A logistic regression analysis was conducted to identify factors associated with choice of adjuvant chemotherapy regimen.Results：Data from 3,020 patients were included.The most frequently used adjuvant regimen was docetaxel/anthracycline combination[n=1,421（47.1%）;of whom 52.0%received T/epirubicin（E）/cyclophosphamide（C）],followed by docetaxel/other[n=705（23.3%）;of whom 72.8%received TC],docetaxel/anthracycline sequential[n=447（14.8%）;of whom 40.9%and 39.6%received 5-Fu/EC-T and EC-T,respectively],and＂other＂[n=447（14.8%）;of whom 91.5%received T].A significant association was found between adjuvant therapy with docetaxel/anthracycline combination and patient weight,menopausal status and estrogen receptor status.Conclusions：Real-world data revealed that docetaxel/anthracycline combination is the most commonly used category of docetaxel-based adjuvant therapy for patients with operable breast cancer in China;of which TEC is the most frequently used regimen.

Surface-enhanced Raman spectroscopy of serum predicts sensitivity to docetaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

Docetaxel-based chemotherapy,as the first-line treatment for metastatic castration-resistant prostate cancer(mCRPC),has succeeded in helping quite a number of patients to improve quality of life and prolong survival time.However,almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially.This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy(SERS).A total of 32 mCPRC patients who underwent docetaxel chemo-therapy at our center from July 2016 to March 2018 were included in this study.Patients were dichotomized in prostate-specific antigen(PSA)response group(n=17)versus PSA failure group(n=15)according to the response to docetaxel.In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline(q0)and after 1 cycle of docetaxel chemotherapy(ql).Comparing Raman peaks of serum samples at baseline(q0)be-tween two groups,significant differences revealed at the peaks of 638,810,890(p<0.05)and 1136cm^(-1)(p<0.01).The prediction models of peak 1363 cm^(-1)and principal component anal-ysis and linear discriminant analysis(PCA-LDA)based on Raman data were established,re-spectively.The sensitivity and specificity of the prediction models were 71%,80%and 69%,78%through the way of leave-one-out cross-validation.According to the results of five-cross-valida-tion,the PCA-LDA model revealed an accuracy of 0.73 and AUC of 0.83.

Low-Dose Metronomic Chemotherapy in Metastatic Breast Cancer: A Retrospective Analysis of 40 Patients

Purpose: Low-dose metronomic chemotherapy is an emergent treatment schedule in which low doses of cytotoxic agents are given orally continuously, with no or short drug-free intervals. In general, it provides better tolerance, especially in patients who have been previously exposed to other oncologic treatments, with a favorable cost-effectiveness profile. It is well known that all these low-dose schedules have a favorable safety profile and may provide an adequate tumor control in patients with metastatic breast cancer. However, there are no data in literature reporting the patient’s tolerance and response to subsequent lines of chemotherapy after receiving metronomic regimens. Methods: We retrospectively analyzed 40 patients with metastatic breast cancer treated with low doses of Cyclophosphamide and/or Methotrexate and/or Capecitabine in a single center from June 2009 to April 2014. The following data were collected: age, hormone and epidermal growth factor receptor 2 (HER-2) status, number of lines of chemotherapy prior to and after low-dose metronomic treatment, duration of metronomic treatment, toxicity reason for treatment discontinuation. Duration of low-dose metronomic chemotherapy was also correlated with the variables analyzed and treatment outcomes. Results: The median time on metronomic chemotherapy was 5.4 months. The most frequent drugs administered were cyclophosphamide, methotrexate and capecitabine alone. Asthenia, myelotoxicity, gastrintestinal symptoms and handfoot syndrome were the most commonly recorded treatment related toxicity. Twenty six (65%) patients had the opportunity to receive a classic chemotherapy regimen following metronomic regimen interruption. Although patients who developed toxicity to low-dose metronomic chemotherapy remained less time (<6 months) in subsequent chemotherapy, there was no statistically significant difference among those who received more lines of chemotherapy. Discussion: This is the first report in the literature describing the efficacy of low-dose metronomic regimens and the tolerance to subsequent lines of treatments following a period of metronomic chemotherapy. Most of our patients were able to tolerate conventional chemotherapy regimens administered in full doses. Several patients received as many as three lines of additional chemotherapy for periods that exceeded 6 months of treatment, which suggests that the use of prolonged metronomic treatment does not affect a patient’s ability to tolerate subsequent therapy.

BRCA1 and EGFR as prognostic biomarkers in triple negative metastatic breast cancer patients treated with cisplatin plus docetaxel

Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressive chemotherapy regimens. This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer, and the possibility of using breast cancer susceptibility genel （BRCA1） expression as a predictive marker of chemotherapy response, and epidermal growth factor receptor （EGFR） as prognostic marker. Method： Between January 2006 and March 2009, 40 eligible patients with TN MBC were included in the study. We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry. The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks, TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study. Results： The median age of the treated patients was 43.5 years. Nearly half of the patients had an ECOG performance status of 0 or 1, and about third of them had one metastatic site. These metastatic sites were predominantly visceral in 80% of the patients. Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR. Positivity for both markers was significantly associated with grade III tumors （P = 0.004）, OS, and PFS （P = 0.001 and 0.009） respectively. Overall, the regimen was well tolerated as Gill vomiting and neurological side effects were observed in 20% of the patients. Other toxiciUes were generally mild and medically manageable; with no treatment mortality was recorded. The overall disease control rate （ODCR） was 60%; the median PFS was 8 months, with a median overall OS of 17.5 months; while the median OS among responders was 23 months （95% CI 21.35 to 25.32）. The patients with negative EGFR had a significantly better OR, PFS, and OS than EGFR positive cases. There was no significant difference concerning OR, PFS, and OS, between positive and negative BRCA1 cases, which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases. Conclusion： This chemotherapy regimen is effective with tolerable toxicity profile, our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response, and EGFR as prognostic marker, which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.

Quality of Life of Patients with Metastatic Breast Cancer Treated with Epirubicin and Docetaxel

This phase II study assessed the clinical response and short-term quality of life of patients receiving first-line chemotherapy with epirubicin-docetaxel combination for metastatic breast cancer. Thirty-one breast cancer patients were treated with epirubicin (75 mg/m2 for 15 minutes) followed one hour later by a one-hour infusion of docetaxel (75 mg/m2) q3w. EORTC QLQ-C30 and EORTC QLQ-BR23 forms were filled in at baseline, and at the second and eighth cycle of chemotherapy. The combination of epirubicin and docetaxel provided a high degree of clinical benefit. Clinical response was observed in 17 patients (55%), including five (16%) complete responses and 12 (39%) partial responses. Of responding and stable patients 23 (74%) maintained the same status for at least six months (clinical benefit). The mean survival time was 40.8 months. During the treatment the emotional functioning improved and the concerns about the future were relieved. Some aspects of quality of life were impaired, with slightly decreased physical and cognitive functioning, distress related to body image and hair loss, and adverse effects of chemotherapy. Overall, the global quality of life was maintained.

Docetaxel and cisplatin combination chemotherapy in anthracyclines-resistant advanced breast cancer

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.

Significance of serum carcinoembryonic antigen in metastatic breast cancer patients:A prospective study

BACKGROUND Carcinoembryonic antigen(CEA)is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours.About 36%-70%of breast cancers have elevated serum CEA.And the available studies show discrepancy in addressing the prognostic significance of CEA in advanced breast cancer.AIM To estimate the serum CEA level in our metastatic breast cancer patients and correlate it with response to treatment and clinical outcome.METHODS This was a prospective clinical study conducted on 50 metastatic breast cancer patients treated at breast clinic,with newly diagnosed metastatic breast cancer planned for palliative chemotherapy,targeted therapy,and hormonal treatment.We estimated the proportion of patients with elevated serum CEA level at baseline and after palliative treatment and also studied the association of serum CEA levels with known prognostic factors.The response to treatment was correlated with the serum CEA levels in the context of responders and nonresponders.RESULTS The median pre-treatment and post-treatment CEA levels were 7.9(1.8-40.7)ng/mL and 4.39(1.4-12.15)ng/mL,respectively,in the whole study population(P=0.032).No statistically significant difference was seen in baseline serum CEA between responders and non-responders.Even in the luminal group,pretreatment serum CEA was not a predictor of response,but post-treatment CEA was a significant predictor of tumour progression.In patients with liver and lung metastases,post-treatment CEA level difference was not statistically significant in both responders and non-responders though the values were higher in nonresponders.Among those with bone metastases,69.5%had elevated post-treatment serum CEA,and only 37.5%had elevated serum CEA in those with no bone metastases.CONCLUSION Elevated post-treatment serum CEA levels are associated with disease progression and poor response to therapy.Persistently elevated post-treatment serum CEA levels are significantly associated with bone metastases.Elevated serum CEA and hormonal status are significant predictors of treatment response.

Inetetamab combined with sirolimus and chemotherapy for the treatment of HER2‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR pathway after trastuzumab treatment

Background:We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2(HER2)‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR(PAM)pathway after trastuzumab treatment.Methods:For this prospective multicenter clinical study,HER2‐positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022.Patients were randomly assigned to a trial or control group.The patients in the trial group received inetetamab combined with sirolimus and chemotherapy,while the control group patients received pyrotinib and chemotherapy.The RECIST v1.1 standard was used to evaluate efficacy.Descriptive statistics were used to summarize the clinicopathological features,and the Kaplan–Meier method was used to generate survival curves.The log‐rank test was used to compare progression‐free survival(PFS)between the two groups.Results:A total of 59 HER2‐positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included,of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment.The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group,with no statistically significant difference(p=0.507).The objective response rates were 27.3%for the inetetamab group and 29.4%for the pyrotinib group.The safety assessment indicated that the adverse event(AE)incidences were 86.1%(31/36)in the inetetamab group and 78.9(15/19)in the pyrotinib group,with 9(25%)and four(21.1%)Grade 3/4 AEs in the inetetamab and pyrotinib groups,respectively.Conclusions:For metastatic HER2‐positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment,the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy.Therefore,this regimen could be a treatment option for PAM pathway‐activated metastatic HER2‐positive breast cancer patients.

Capecitabine combined with weekly docetaxel in Chinese patients 〉65 years with anthracycline-resistant metastatic breast cancer

Background There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer （MBC） in older Chinese patients. Methods MBC patients aged 〉65 years pretreated with 1-5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m^2 twice daily, days 1-14, plus docetaxel 30 mg/m^2 on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles （median 4, range 2-8） and were evaluable for efficacy. Results The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia （12%）, alopecia （7%）, grade 3 nausea and vomiting （2%） and grade 3 nail toxicity （2%）. Conclusions Capecitabine 825 mg/m^2 twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women 〉65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.

Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience

BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer.There are currently few reports on the pattern of use and value of Pertuzumab in real world settings.Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted.Demographic and clinical data were extracted from electronic medical records.Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.RESULTS Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline therapy.With a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)cardiotoxicity.The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group.The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity.However,the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.

The clinical observation of neoadjuvant chemotherapy in locally advanced breast cancer with DX regimen

The recent clinical curative effect and adverse events of docetaxel and capecitabine （DX） of neo- adjuvant chemotherapy in patients with locally advanced breast cancer was discussed. Methods： The data of 72 cases of neoadjuvant chemotherapy （DX） in locally advanced breast cancer after 4 cycles were retrospectively analyzed. Docetaxel 75 mg/m^2 by infusion 1 h on dl, capecitabine 2000 mg/m^2 by oral for twice daily on d1-14, 21 days was a cycle. Results： All 72 patients were assessed for efficacy and adverse events. The total effective rate was 80.5% （58/72）, including pathological complete response （pCR） was 7 （9.7%）, clinical complete remission （cCR） was 15（20.8%）, clinical partial response （PR） was 43 （59.7%）, stable disease （SD） was 8 （11.1%） and progressive disease （PD） was 6 （8.3%）. The main adverse events were gastrointestinal reactions and bone marrow suppression. The 3 to 4 degrees of adverse reactions including granulocytopenia in 7 patients （20.6%）, hand-foot syndrome in 6 patients （15.2%）. Conclusion： The DX regimen provide a favorable efficacy and safety profile in patients with locally advanced breast cancer for neoadjuvant chemotherapy.

Impact of Diabetes Mellitus on the Treatment Outcomes of Chemotherapy in Women with Breast Cancer——A Population-Based Prospective Cohort Study

There are few population-based data in investigating the impact of diabetes on chemotherapy adverse effects and treatment outcomes of non-metastatic breast cancer. The purpose of this study is to evaluate whether diabetes affects the patterns of use in chemotherapy, toxic effects of chemotherapy, and treatment outcomes for non-metastatic breast cancer in Taiwan. The study results can provide physicians for making a decision whether or not to use chemotherapy based on the individual patients＇ condition.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer

Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

Real-world evaluation of upfront docetaxel in metastatic castrationsensitive prostate cancer

BACKGROUND The majority of patients with newly diagnosed metastatic prostate cancer(PC)initially respond to androgen deprivation therapy(ADT)and are classified as metastatic castration-sensitive PC(mCSPC).Following months to years of ADT,the disease tends to become resistant to ADT.Recent randomized phase-III trials demonstrated a survival benefit with the addition of upfront docetaxel to ADT in mCSPC.Following its implementation in routine care,this combined treatment strategy requires more detailed evaluation in a real-world setting.AIM To assess the real-world outcome and safety of upfront docetaxel treatment in mCSPC.METHODS A multicenter retrospective cohort study in the Southeast Health Care Region of Sweden was performed.This region includes approximately 1.1 million citizens and the oncology departments of Linköping,Jönköping,and Kalmar.All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included.The primary endpoint was progression-free survival(PFS)at 12 mo,and the secondary endpoints were PFS at 24 mo,overall survival(OS),treatment intensity,adverse events,and unplanned hospitalizations.Exploratory analyses on potential prognostic parameters were performed.RESULTS Ninety-four patients were eligible and formed the study cohort.PFS at 12 and 24 mo was 75%(95%CI:66–84)and 58%(46–70),respectively.OS at 12 and 24 mo was 93%(87–99)and 86%(76–96).A total of 91%of patients(n=86)were given docetaxel according to the standard protocol of 75 mg/m2 every 3 wk(6 cycles),while 9%(n=8)received a modified protocol of 50 mg/m2 every 2 wk(9 cycles).The average overall dose intensity for those commencing standard treatment was 91%.Univariate Cox regression analyses show that baseline PSA>180 vs<180 and the presence of distant metastases vs locoregional lymph node metastases were only negative prognostic factors(HR 2.86,95%CI:1.39–5.87,P=0.0041 and 3.36,95%CI:1.03–10.96,P=0.045).Following multivariate analysis,statistical significance remained for PSA(2.51,95%CI:1.21–5.19,P=0.013)but not for metastatic status(2.60,95%CI:0.78–8.65,P=0.12).Febrile neutropenia was recorded in 21%(n=20)of patients,and 26%(n=24)had at least one episode of unplanned hospitalization under and up to 30 d after the treatment course.CONCLUSION Results from this study support the implementation of upfront docetaxel plus ADT as part of the standard of care treatment strategy in mCSPC.

Albumin-based multidrug delivery system enriched in Golgi apparatus against metastatic breast cancer

Breast cancer and metastasis remain great challenges in clinical therapy.Compared with monotherapy,combination therapy,especially mediated by nanomedicine delivery strategy,significantly improves the therapeutic efficacy and reduces undesired toxicity.Cyclooxygenase-2(COX-2)inhibitors are widely used for adjuvant chemotherapy because COX-2 is overexpressed in virtually all cancer cell lines to regulate tumor progression by catalyzing prostaglandin E2(PGE2)synthesis.This drug combination strategy is still required to be improved due to some unsatisfactory clinical trial results.Intricate processes of tumor growth and metastasis are orchestrated by multiple proteins in addition to COX-2,which are modified and transported by Golgi apparatus.Hence,disrupting the structure and function of Golgi apparatus can inhibit the secretion of tumor-related proteins and further suppress carcinoma progression and metastasis.Since COX-2 is also enriched within Golgi apparatus in tumor cells,COX-2 inhibitors and Golgi disrupting agents can be co-delivered to Golgi apparatus to maximize the synergy.In this work,we developed a human serum albumin(HSA)nanoparticle encapsulating pirarubicin(THP),retinoic acid(RA),and indomethacin(IMC),called TIR-HSA,which was observed to be localized in Golgi complex of 4T1 cells.Owing to the synergistic effect of these three drugs,TIR-HSA inhibited the proliferation,migration,and invasion of tumor cells,enhanced the apoptotic rate,and improved the immunosuppressive tumor microenvironment,which remarkably regressed the tumor growth and metastasis and prolonged the survival period of 4T1-bearing mice.

Safety and efficacy of first-line bevacizumab combined with taxane therapy in Chinese patients with HER2-negative locally recurrent or metastatic breast cancer： findings from the ATHENA study

Background Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer （LR/mBC）. However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.

Oral etoposide monotherapy is effective for metastatic breast cancer with heavy prior therapy

Background Treatment option for metastatic breast cancer （MBC） patients pre-treated with chemotherapy is limited. Oral etoposide has shown some promises in these patients. However, patients who received heavy prior chemotherapy may have poor tolerance to prolonged oral etoposide exposure. This study is a single-arm clinical trial that evaluates the efficacy and safety of short-term oral etoposide in Chinese patients with MBC who had received heavy prior therapy.