Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2(HER2)-positive early-stage breast cancer: A real-world retrospective study in Chinese patients

Objective: To assess the long-term effectiveness and safety of trastuzumab in adjuvant therapy for Chinese patients with early-stage human epidermal growth factor 2(HER2)-positive breast cancer in a real-world setting.Methods: This retrospective observational study analyzed the medical records of HER2-positive breast cancer patients between 2000 and 2012 at the Chinese Academy of Medical Sciences. Patients who received adjuvant chemotherapy alone or adjuvant chemotherapy followed by/combined with trastuzumab were included. The Kaplan-Meier method was used to estimate disease-free survival(DFS) and overall survival(OS). Hazard ratios(HR) and 95% confidence intervals(95% CI) were calculated using the Cox regression model.Results: Of the 1,348 patients analyzed, 909 received chemotherapy alone and 439 received chemotherapy plus trastuzumab. The 3-year, 5-year and 10-year DFS rates were 83.70%, 76.38% and 68.94%, respectively, in the chemotherapy-alone cohort, and 90.21%, 86.19% and 83.45% in the chemotherapy plus trastuzumab cohort. The3-year, 5-year and 10-year OS rates were 96.10%, 91.40% and 81.88% in the chemotherapy-alone cohort, and98.17%, 94.91% and 90.01% in the chemotherapy plus trastuzumab cohort. The chemotherapy plus trastuzumab group had a significantly lower risk of disease recurrence and death than the chemotherapy-alone group(DFS:HR=0.50, 95% CI, 0.37-0.68;P<0.001;OS: HR=0.53, 95% CI, 0.34-0.81;P=0.004) after adjusting for covariates.In the 439 patients treated with trastuzumab, multivariate analysis suggested that lymph node positivity, higher T stages, and hormone receptor-negative status were significantly associated with higher risks of disease recurrence,and lymph node positivity and hormone receptor-negative status were significantly associated with higher risks of death. Grade 3/4 adverse events(incidence ≥1%) were more common in patients receiving trastuzumab(54.44% vs.15.73%).Conclusions: Early-stage HER2-positive breast cancer patients treated with trastuzumab plus adjuvant chemotherapy have a significant survival benefit compared with chemotherapy-alone in real-world settings. Lymph node positivity, hormone receptor-negative status, and higher T stages may be associated with higher risks of recurrence, and effective therapy for patients with these factors is required.

Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines

Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960 s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclinesin the adjuvant setting for patients with breast cancer. We consulted Pub Med, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.

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.

Dose-dense paclitaxel plus carboplatin vs.epirubicin and cyclophosphamide with paclitaxel as adjuvant chemotherapy for high-risk triple-negative breast cancer

Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.

Accuracy of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients;Single Center Experience

Purpose: Most important factor affecting prognosis of breast cancer is axillary nodal involvement. Several studies evaluated the accuracy of Sentinel lymph node biopsy in breast cancer patients post neoadjuvant chemotherapy. In this study, we will examine accuracy and feasibility of using Sentinel lymph node biopsy in predicting axillary lymph node status in breast cancer patients after neoadjuvant chemotherapy. Methods: 45 female patients with resectable, nonmetastatic breast carcinoma cases who received neoadjuvant chemotherapy were enrolled in this study according to the routine Mansoura Oncology Center—guidelines of management of breast cancer. Methylene blue dye used for detection of Sentinel lymph node. Results: Successful Sentinel lymph node detection was 82.2%. Skin involvement (T4 disease) were linked to a low identification (P = 0.005). False negative rate equals 11/27 = (40.7%).With advancement of the stage of the tumor, the incidence of false negative results increases significantly (p = 0.012) with 95% confidence interval;1.2 - 5.4. Conclusion: Sentinel lymph node should be adopted to be the standard method for axillary staging with T1-3 tumors after receiving neoadjuvant chemotherapy, in T4 patients, it is associated with low detection rate & high false negative rate making it doubtful technique for axillary staging.

Impact of adjuvant chemotherapy delay on survival in cancer breast patients

Objective： The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. It is usually prescribed within 2-3 months after definitive surgery. The aim of this retrospective study was to assess the impact of adjuvant chemotherapy （CT） delay beyond 3 weeks （ 21 days） in premenopausal patients with ER-absent tumors being treated for early stages breast cancer on overall survival （OS） and disease-free survival （DFS）. Methods： This retrospective study was conducted through revision of medical records of premenopausal patients diagnosed with early stage ｜-｜IIA breast cancer and ER-absent tumors who received adjuvant CT after definitive surgery at the Department of Clinical Oncology, Ain-Shams University Hospitals. Results： Between 2005 and 2008, 105 patients were retrospectively analyzed and included. Patients were divided into 2 groups： Group A including 48 patients who started adjuvant CT 〈 21 days of surgery and group B which included 57 patients who had CT delay 〉 21 days. Both groups were matched demographically. Comparisons of overall survival, and disease-free survival between group A and group B patients all favored group A. At 5-year the OS rates were 87% and 73% for groups A and B respectively （P = 0.001）, while DFS rates were 85% and 64% in groups A and B respectively （P = 0.001）. Analysis of other prognostic factors （age, T, N, grade, HER2 status, surgery type, CT type, local radiotherapy received） were analyzed. Only nodal status predicted for worse DFS （P = 0.05） and OS （P = 0.006）. Conclusion： Delay in initiating adjuvant chemotherapy for early stage breast cancer patients with ER-absent tumors was associated with a decrease in both OS and DFS rates.

Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery？

Objective: Survival and treatment of patients with microinvasive breast cancer(MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy.Methods: In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer(AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups.We compared the 5-year disease-free survival(DFS) and overall survival(OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months(13-104months).Results: The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the nonchemotherapy group were 89.7% and 100%. Results indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS(P=0.223) or OS(P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2% vs. 86.5% between low Ki-67(≤20%) and high Ki-67(>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval(CI), 1.969-139.724; P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149(95% CI, 3.702-99.057; P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients(P=0.014), but not those who overexpress Ki-67(P=0.105).Conclusions: Patients with MIBC who overexpress Ki-67 and with negative hormonal receptors have relatively substantial risk of relapse within the first five years after surgery. However, adjuvant chemotherapy can only improve the outcomes of ER(-)/PR(-)patients, but not those who overexpress Ki-67. Further studies with prolonged follow-up of large cohorts are recommended to assess the prognostic significance and treatment of this lesion.

A nomogram to predict adjuvant chemotherapy recommendation in breast cancer patients with intermediate recurrence score

Objective： The indication of adjuvant chemotherapy recommendation（ACR） in breast cancer patients with intermediate recurrence score（RS） is controversial. This study investigated the relationship between routine clinicopathological indicators and ACR, and established a nomogram for predicting the probability of ACR in this subset of patients.Methods： Data for a total of 504 consecutive patients with intermediate RS from January 2014 to December2016 were retrospectively reviewed. A nomogram was constructed using a multivariate logistic regression model based on data from a training set（378 cases） and validated in an independent validation set（126 cases）. A Youdenderived cut-off value was assigned to the nomogram for accuracy evaluation.Results： The multivariate logistic regression analysis identified that age, histological grade, tumor size, lymph node（LN） status, molecular subtype, and RS were independent predictors of ACR. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.286. The area under the curve（AUC） values were 0.905 [95% confidence interval（95% CI）： 0.876–0.934] and 0.883（95%CI： 0.824–0.942） in the training and validation sets, respectively. The accuracies of the nomogram for ACR were84.4% in the training set and 82.1% in the validation set.Conclusions： We developed a nomogram to predict the probability of ACR in breast cancer patients with intermediate RS. This model may aid the individual risk assessment and guide treatment decisions in clinical practice.

Systemic oncological therapy in breast cancer patients on dialysis

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.

Neoadjuvant endocrine therapy: A potential strategy for ER-positive breast cancer

A potential strategy for patients with estrogen receptor(ER)-positive breast cancer is necessary to replace neoadjuvant chemotherapy which has limited benefit.Neoadjuvant endocrine therapy(NAE)has been indicated to be a favorable alternate approach to downstage large or locally advanced breast cancer in ER-positive,human epidermal growth factor receptor 2(HER2)-negative(ER+/HER2-)patients,especially postmenopausal women.Previous studies have demonstrated the efficacy of various endocrine agents in NAE.Aromatase inhibitors(AIs)have proven superiority over tamoxifen as a suitable choice to optimize treatment efficacy.Fulvestrant was recently reported as an effective agent,similar to AIs.Furthermore,the addition of targeted agents exerts synergistic antiproliferative effects with endocrine agents and rapidly improves response rates in both endocrine sensitive and resistant tumors.The neoadjuvant platform provides a unique opportunity to define the appropriate strategy and address the mechanisms of endocrine resistance.In addition,the predictive value of biomarkers and genomic assays in NAE is under investigation to evaluate individual effects and validate biomarker-based strategies.In this review,we discuss the most relevant evidence on the potential of NAE for ER+breast cancer.The current understanding also offers new insights into the identification of the optimal settings and valuable predictive tools of NAE to guide clinical treatment decisions and achieve beneficial therapeutic effects.

Metronomic chemotherapy for non-metastatic triple negative breast cancer: Selection is the key

Triple negative breast cancer(TNBC) accounts for 15%-20% of all breast cancer, and is still defined as what it is not. Currently, TNBC is the only type of breast cancer for which there are no approved targeted therapies and maximum tolerated dose chemotherapy with taxanes and anthracycline-containing regimens is still the standard of care in both the neoadjuvant and adjuvant settings. In the last years, metronomic chemotherapy(MC) is being explored as an alternative to improve outcomes in TNBC. In the neoadjuvant setting, purely metronomic and hybrid approaches have been developed with the objective of increasing complete pathologic response(p CR) and prolonging disease free survival. These regimens proved to be very effective achieving pC R rates between 47%-60%, but at the cost of great toxicity. In the adjuvant setting, MC is used to intensify adjuvant chemotherapy and, more promisingly, as maintenance therapy for high-risk patients, especially those with no pC R after neoadjuvant chemotherapy. Considering the dismal prognosis of TNBC, any strategy that potentially improves outcomes, specially being the oral agents broadly available and inexpensive, should be considered and certainly warrants further exploration. Finally, the benefit of MC needs to be validated in properly designed clinical trials were the selection of the population is the key.

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.

Adjuvant Chemotherapy of Gemcitabine plus Carboplatin versus Paclitaxel plus Carboplatin in Patients with Resected Non-Small Cell Lung Cancer

Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29;PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%;PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%;PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%;PC: 13/15, 86.7%, p 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.

Beneficial effects of auricular acupressure on preventing constipation in breast cancer patients undergoing chemotherapy:evidence from systematic review and meta-analysis

Objective： To evaluate the available evidence from randomized controlled trials （RCTs） of auricular acupressure （AA） therapy for preventing constipation in breast cancer patients undergoing chemotherapy. Methods： The following databases were searched from their inception until August 2017： Ovid Medline, Embase, the Cochrane Central Register of Controlled Trials （CENTRAL）, and Allied and Alternative Medieine （AMED）. We also searched four Chinese databases： Chinese BioMedical Database （CBM）, China National Knowledge Infrastructure （CNKI）, WANFANG Data, and Chinese VIP Database. Only the RCTs related to the effects of AA therapy on preventing constipation in breast cancer patients undergoing chemotherapy were included in this study. Quantitative syntheses of data from RCTs were conducted using RevMan 5.3 software. Study selection, data extraction, and validation were performed independently by two authors. Cochrane criteria for risk of bias were used to assess the methodological quality of the trials. Results： Four RCTs met the inclusion criteria, and most were of low methodological quality. Study participants in the AA plus routine care group showed significantly greater improvements in the response rate （risk ratio [RR] = 1.27, 95% confidence interval [CI] [1.14, 1.42], P 〈 0.01） with low heterogeneity （x2=2.31, P =0.31, F = 14%）. In addition, when compared with routine care alone, one RCT suggested favorable statistically significant effects of AA plus routine care on Constipation Assessment Scale （CAS; mean difference [MD] =-5.07, 95% CI [-6.86, -3.28], P 〈 0.01）. Furthermore, when compared with routine care alone, one RCT suggested positive statistically significant effects of AA plus routine care on Patient Assessment of Constipation-Quality of Life （PAC-QOL; MD = -1.26, 95% CI [-1.59, -0.93], P 〈 0.01）. Conclusions： Overall, as a potential safety therapy, only weak evidence can support the hypothesis that AA can effectively prevent constipation in breast cancer patients undergoing chemotherapy.

Increased Mortality Risk among Early Stage Hormone Receptor Positive Breast Cancer Patients Who Did Not Receive Adjuvant or Neoadjuvant Therapy

Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer. Although adjuvant therapy has demonstrated a survival benefit in clinical trials, its use is poorly understood in the real-world among elderly breast cancer patients since age is a barrier to receiving adjuvant therapy. An examination of treatment patterns and outcomes associated with receipt of adjuvant/neoadjuvant therapy among elderly HR + HER2-breast cancer patients was undertaken. Methods: There were 18,470 HR + HER2-breast cancer patients from the linked SEER-Medicare database. Patients were diagnosed with stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, enrolled in Medicare Parts A, B and D, and underwent breast cancer surgery after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival. Results: There were 13,670 (74%) patients treated with adjuvant/neoadjuvant therapy and 4800 (26%) untreated. Compared to treated patients, untreated patients were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity score, and less use of a 21-gene recurrence score (RS) assay (p < 0.0001). In the survival model, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of an RS assay was associated with lower risks. The Cox model showed a 48% higher risk of death in untreated compared to treated patients. In a subset of 8967 patients with stage I disease, tumor size < 2.0 cm and grade 1/2;untreated patients had a 22% higher risk of death compared to treated patients. Conclusions: Older patients with favorable clinical characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to adjuvant/neoadjuvant treated patients. An unmet need among older breast cancer patients persists.

Edmonton Symptom Assessment Scale may reduce medical visits in patients undergoing chemotherapy for breast cancer

BACKGROUND Adjuvant chemotherapy is recommended in high-risk breast cancer. However, no universally accepted guidelines exist on pre-chemotherapy assessment. In particular, the number and frequency of medical visits vary according to each institution’s policy. We hypothesised that the Edmonton Symptom Assessment Scale(ESAS) may have a favourable impact on the pre-treatment assessment in candidates for adjuvant chemotherapy.AIM To investigate whether the ESAS can be used to safely reduce the number of medical visits in women with breast cancer undergoing adjuvant chemotherapy.METHODS In a retrospectively prospective matched-pair analysis, 100 patients who completed the ESAS questionnaire before administration of adjuvant chemotherapy(ESAS Group) were compared with 100 patients who underwent chemotherapy according to the traditional modality, without ESAS(no-ESAS Group). Patients of the ESAS Group received additional visits before treatment if their ESAS score was > 3. The primary endpoint was the total number of medical visits during the entire duration of the chemotherapy period. The secondary endpoints were the occurrence of severe complications(grade 3-4) and the number of unplanned visits during the chemotherapy period.RESULTS The study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group(age P = 0.880;breast cancer stage P = 0.56;cancer histology P = 0.415;tumour size P = 0.258;lymph node status P = 0.883;immunohistochemical classification P = 0.754;type of surgery P = 0.157), except for premenopausal status(P = 0.015). The study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group regarding age, cancer stage, histology, tumour size, lymph node status, immunohistochemical classification, and type of surgery. Unplanned visits during the entire duration of chemotherapy were 8 in the ESAS Group and 18 in the no-ESAS Group visits(P = 0.035). Grade 3-4 toxicity did not differ between the study groups(P = 0.652). Forty-eight patients of the ESAS Group received additional visits due to an ESAS score > 3. The mean number of medical visits was 4.38 ± 0.51 in the ESAS Group and 16.18 ± 1.82 in the no-ESAS group(P < 0.001). With multivariate analysis, women of the ESAS group were more likely to undergo additional visits for an ESAS score > 3 if they were aged 60 or older, received a mastectomy, or had tumour stage Ⅱ/Ⅲ.CONCLUSION The ESAS score may safely reduce the number of medical visits in candidates for adjuvant chemotherapy for early breast cancer. Our results suggest that the ESAS score may be used for selecting a group of breast cancer patients for whom it is safe to reduce the number of medical visits in the setting of adjuvant chemotherapy. This may translate into several advantages, such as a more rational utilization of human resources and a possible reduction of coronavirus pandemic infection risk in oncologic patients.

A retrospective clinical study of safety and efficacy of vinorelbine/epirubicin/fluorouracil(NEF) regimen as a postoperative chemotherapy for breast cancer

Objective： We aimed to investigate the safety and efficiency of vinorelbine/epirubidn/fluorouracil （NEF） regimen as adjuvant chemotherapy for breast cancer. Methods： From 2005 to 2008, 227 female breast cancer patients were treated with the NEF regimen： vinorelbine 25 mg/m^2 iv on days 1 and 8; epirubicin 60 mg/m2 iv gtt on day 1; 5-Fu 500 mg/m2 iv gtt on day 1. Chemotherapy was repeated every 21-28 days for a total of 6 cycles. Results： The major side effects were neutrope- nia and gastrointestinal syndrome, with a 5-year survival rate of 85.4%, Conclusion： NEF regimen is safe and guarantees a high survival rate which could be recommended as a adjuvant chemotherapy regimen for breast cancer,

Impact of regular enteral feeding via jejunostomy during neo-adjuvant chemotherapy on body composition in patients with oesophageal cancer

BACKGROUND Malnourishment and sarcopenia are well documented phenomena in oesophageal cancer.Patients undergoing neo-adjuvant chemotherapy prior to oesophagectomy have complex nutritional needs.AIM To examine the effect of regular nutritional support via feeding jejunostomy on overall body composition in patients undergoing neo-adjuvant chemotherapy prior to oesophagectomy for oesophageal cancer.METHODS Retrospective data were collected for 15 patients before and after neo-adjuvant chemotherapy.All patients had feeding jejunostomies inserted at staging laparoscopy prior to neo-adjuvant chemotherapy and underwent regular jejunostomy feeding.Changes in body composition were determined by analysis of computed tomography imaging.RESULTS Patient age was 61.3±12.8 years,and 73%of patients were male.The time between start of chemotherapy and surgery was 107±21.6 d.There was no change in weight(74.5±14.1 kg to 74.8±13.1 kg)and body mass index(26.0±3.8 kg/m^2 to 26.1±3.4 kg/m^2).Body composition analysis revealed a statistically significant decrease in lumbar skeletal muscle index despite regular feeding(45.8±8.0 cm^2/m^2 to 43.5±7.3 cm^2/m^2;P=0.045).The proportion of sarcopenic patients increased(33.3% to 60%).Six patients(40%)experienced dose-limiting toxicity during chemotherapy.CONCLUSION Regular jejunostomy feeding during neo-adjuvant chemotherapy can maintain weight and adipose tissue.Feeding alone is not sufficient to maintain muscle mass.Further insight into the underlying processes causing reduced muscle mass in cancer patients may help to provide targeted interventions.

Perioperative chemotherapy for resectable gastric cancer:MAGIC and beyond

Over the last 15 years, there have been major advances in the multimodal treatment of gastric cancer, in large part due to several phase Ⅲ studies showing the treatment benefits of neoadjuvant and adjuvantchemotherapy and chemoradiation protocols. The objective of this editorial is to review the current highlevel evidence supporting the use of chemotherapy, chemoradiation and anti-HER2 agents in both the neoadjuvant and adjuvant settings, as well as to provide a clinical framework for use of this data based on our own institutional protocol for gastric cancer. Major studies reviewed include the SWOG/INT 0116, Medical Research Council Adjuvant Gastric Infusional Chemotherapy(MAGIC), CLASSIC, ACTS-GC, Adjuvant Chemoradiation Therapy in Stomach Cancer(ARTIST) and Trastuzumab for Gastric Cancer trials. Although these studies have demonstrated that multiple approaches in terms of the timing and therapy for gastric cancer are effective, no standard of care is widely accepted and questions regarding the optimal timing of chemotherapy, the benefit of radiotherapy, the minimum required extent of lymphadenectomy and optimal chemotherapy regimen still exist. Protocols from the upcoming ARTIST Ⅱ, CRITICS, TOPGEAR, Neo-AEGIS and MAGIC-B studies are outlined, and results from these studies will provide critical information regarding optimal timing and treatment regimen. Additionally, the future directions of gastric cancer research predicated on molecular profiling and tailored therapies based on targetable genetic alterations in individual patient's tumors are addressed.

Recent developments in palliative chemotherapy for locally advanced and metastatic pancreas cancer

In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil.Since then,clinical trials have explored the pharmacokinetic modulation of Gem by fixed dose administration and the combination of Gem with other cytotoxic or the biologically"targeted"agents.However,promising trial results in small phaseⅡtrials have not translated into survival improvements in larger phaseⅢrandomized trials in the advanced disease setting.Two trials have recently reported modest survival improvements with the use of combination treatment with Gem and capecitabine(United Kingdom National Cancer Research GEMCAP trial) or erlotinib(National Cancer Institute of CanadaClinical Trials Group PA.3 trial) .This review will focus on the use of systemic therapy for advanced and metastatic pancreatic cancer,summarizing the results of several recent clinical trials and discuss their implications for clinical practice.We will also discuss briefly the second-line chemotherapy options for advanced pancreatic cancer.