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.

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.

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.

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.

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.

Randomized Trial Comparing Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF) Regimen with Rotational CMFEV Regimen (E=Epirubicin, V=Vincristine) as Adjuvant Chemotherapy in Moderate Risk Operable Breast Carcinoma

Objectives: The CMFEV (cyclophosphamide, methotrexate, 5-fluorouracil, epirubicin, vincristine) regimen is an innovative schedule, designed by our Group, aimed at administering five partially or totally no cross-resistant cytotoxic agents in breast carcinoma. It was randomly compared to CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as primary treatment in operable disease and demonstrated a short-term significant increase in clinical complete response rate and a long-term significant locoregional relapse-free survival in premenopausal patients. So, it seemed worth comparing this regimen with CMF as adjuvant chemotherapy in moderate risk operable breast carcinoma. Methods: Four hundred and eighty-nine patients with stage I or II moderate risk breast carcinoma were randomized to receive CMF or CMFEV regimen for 6 cycles after surgery. Main end points were overall survival (OS), invasive disease-free survival (IDFS) and recurrence-free interval (RFI), as estimated by Kaplan-Meier analyses and log-rank tests. Results: At a median observation time of 7.3 years (range 5.4 months-10.3 years), no significant differences in OS and IDFS were observed between the two arms. Deaths from breast carcinoma were more frequent with CMF (58.5%) than with CMFEV regimen (41.7%) as well as recurrences from breast carcinoma (58.8% with CMF and 41.2% with CMFEV). These differences were not statistically significant. Conclusion: CMFEV appears more effective than CMF in preventing recurrences from primary disease in patients with moderate risk stage I-II breast carcinoma. The lack of statistical significance of the observed differences was probably due to the limited number of patients enrolled which rendered the study underpowdered.

The advance of adjuvant treatment for triple-negative breast cancer

Triple-negative breast cancer(TNBC)is a subtype of breast cancer characterized by its highly aggressive behavior,early recurrence,and poor outcomes,when compared with other subtypes.Due to the absence of the estrogen receptor,progesterone receptor,and human epidermal growth factor receptor 2 expression,TNBC lacks meaningful biomarkers and an effective therapeutic strategy.Chemotherapy remains the main adjuvant treatment for patients with TNBC.Anthracycline/taxane-based regimens are the standard of care in adjuvant settings.The addition of capecitabine or platinum may offer extra benefits to patients with TNBC,but at the cost of increased toxicity or adverse events.Dose-dense chemotherapy may enhance treatment efficacy in patients who are able to tolerate the treatment regimen,especially in high-risk patients.As a heterogenous disease,TNBC can be classified into several molecular subtypes according to genomic or transcriptional features,which may indicate potential targets for more precise and individualized treatment strategies.With our increased understanding of signal pathways associated with TNBC,as well as the discovery of novel biomarkers indicative of TNBC prognosis,several new therapeutic options are under investigation,and some have already reported good results.In this review,we summarized the current conventional therapeutic strategies and emerging clinical trials regarding adjuvant treatment for TNBC.Furthermore,we evaluated the prognostic value of several potential targets and the progress of targeted therapy in TNBC,both in neoadjuvant and adjuvant settings.

The cardiotoxicity and long-term efficacy of different doses of epirubicin in the adjuvant treatment of breast cancer patients: A case control study

Abstract Objective： The aim of the study was to observe the cardiac toxicity caused by different doses of epirubicin in the adjuvant treatment of breast cancer and to evaluate the long-term efficacy. Methods： The 180 cases of breast cancer patients received epirubicin based adjuvant chemotherapy. The patients were randomly assigned to high-dosage group （90 rag/m^2）, medium-dosage group （70 mg/m^2） and low-dosage group （50 rag/m^2）, the primary endpoint was cardiac toxicity. The secondary outcomes were the 5-year overall survival （OS） and 5-year disease-free survival （DFS）. Results： During chemo- therapy, the clinical symptoms such as palpitation, dyspnea and paroxysmal nocturnal dyspnea occurred in 6 patients with the high-dosage group, 4 patients with the medium-dosage group and 3 patients with the low-dosage group. The number of patients who had changed in electrocardiogram （ECG） was 7, 5 and 4 in three groups, respectively. The echocardiographic showed each group had only one case with LVEF 〈 50%, there was no significantly difference （P 〉 0.05）. In the three groups, the 5-year DFS rates were 73.3% （44/60） in high-dose group, 53.3% （32/60） in medium-dose group and 41.6% （25/60） in low dose group. The 5-year OS rates were 85.0% （51/60）, 68.3% （41/60） and 58.3% （35/60） in three groups, respectively. The differences were statistically significant （P 〈 0.05）. Conclusion： The high-dose epirubicin in adjuvant chemotherapy with CEF （cyclophosphamide, epirubicin and fluorouracil） regimen could improve the 5-year OS rate and 5-year DFS rate on patients of breast cancer. The cardiotoxicity was mild-moderate and well tolerated.

Evaluating the benefit of adjuvant chemotherapy in patients with ypT0-1 rectal cancer treated with preoperative chemoradiotherapy

BACKGROUND Adjuvant chemotherapy(ACTx)is recommended in rectal cancer patients after preoperative chemoradiotherapy(PCRT),but its efficacy in patients in the early post-surgical stage who have a favorable prognosis is controversial.AIM To evaluate the long-term survival benefit of ACTx in patients with ypT0–1 rectal cancer after PCRT and surgical resection.METHODS We identified rectal cancer patients who underwent PCRT followed by surgical resection at the Asan Medical Center from 2005 to 2014.Patients with ypT0–1 disease and those who received ACTx were included.The 5-year overall survival(OS)and 5-year recurrence-free survival(RFS)were analyzed according to the status of the ACTx.RESULTS Of 520 included patients,413 received ACTx(ACTx group)and 107 did not(no ACTx group).No significant difference was observed in 5-year RFS(ACTx group,87.9%vs no ACTx group,91.4%,P=0.457)and 5-year OS(ACTx group,90.5%vs no ACTx group,86.2%,P=0.304)between the groups.cT stage was associated with RFS and OS in multivariate analysis[hazard ratio(HR):2.57,95%confidence interval(CI):1.07–6.16,P=0.04 and HR:2.27,95%CI:1.09–4.74,P=0.03,respectively].Furthermore,ypN stage was associated with RFS and OS(HR:4.74,95%CI:2.39–9.42,P<0.00 and HR:4.33,95%CI:2.20–8.53,P<0.00,respectively),but only in the radical resection group.CONCLUSION Oncological outcomes of patients with ypT0–1 rectal cancer who received ACTx after PCRT showed no improvement,regardless of the radicality of resection.Further trials are needed to evaluate the efficacy of ACTx in these group of patients.

Development and controversies of adjuvant therapy for pancreatic cancer

BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES: A Medline database search was performed to identify relevant articles using the keywords 'pancreatic neoplasm', and 'adjuvant therapy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identified. The results for adjuvant regimens based on systemic 5-fluorouracil with or without external radiotherapy were conflicting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS: Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

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.

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for devel- oping anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs~ Alt- hough liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin （PLD） and non-PLD （NPLD） in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on.

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.

A Predictive Model for Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy Using Machine Learning

Background: In patients with breast cancer after Neoadjuvant Chemotherapy (NAC), pathological Complete Response (pCR) was associated with better long-term outcomes. We here attempted to predict pCR using machine learning. Patients and Methods: From 2008 to 2017, 1308 breast cancer patients underwent NAC before surgery, of whom 377 patients underwent Cancer SCANTM for gene data. Of 377, 238 were analyzed here, with 139 excluded due to incomplete medical data. Results: The pCR (-) vs. (+) group had 200 vs. 38 patients. In our predictive model with gene data, the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve was 0.909 and accuracy was 0.875. In another model without gene data, the AUC of ROC curve was 0.743 and accuracy was 0.800. We also conducted internal validation with 72 patients undergoing NAC and Cancer SCANTM during July 2017 and April 2018. When we applied a 0.4 threshold value, accuracy was 0.806 and 0.778 in the predictive model with vs. without gene profiles, respectively. Conclusion: The present predictive model may be a useful and easy-to-access tool for pCR-prediction in breast cancer patients treated with NAC.

Adjuvant therapy for hormone receptor-positive breast cancer: Perspective from a survey on breast cancer physicians' acceptance of practice-changing data

A cross-sectional online survey was conducted.A high proportion of the Chinese breast cancer(BC)physician respondents(n=77)would prescribe extended adjuvant endocrine therapy(AET)with aromatase inhibitors(AI)beyond 5 years for postmenopausal females with BC,especially those with higher risk.Respondents with≥15 years of clinical experience were more likely to prescribe a longer duration of AET for low-risk patients.Half of the respondents considered intermittent letrozole as an acceptable option.Most respondents would prescribe adjuvant chemotherapy to genomic high-intermediate risk[Oncotype DX recurrence score(RS)21-25]females aged≤50 years regardless of the clinical risk classification.

The magnitude of benefit from adding taxanes to anthracyclines in the adjuvant settings of breast cancer:discussion of large trials and meta-analyses

The taxanes family of chemotherapy,which includes paclitaxel and docetaxel,has been incorporated in the adjuvant breast cancer treatments since 1990s.Sequential and concurrent use of taxanes was investigated with anthracyclines in many adjuvant early breast cancer randomized clinical trials.Results from taxanes trials showed inconsistent benefits.However,several meta-analyses showed significant survival benefit of adding taxanes.In this review article,data were collected and summarized from eleven large randomized trials and three meta-analyses to show and discuss the magnitude of benefit of taxanes-anthracyclines combination compared to anthracyclines only adjuvant regimens in early breast cancer.This article aims at providing the oncologists with a well-organized,inclusive and updated evidence.

Adjuvant Taxanes in Breast Cancer: A Critical Re-appraisal

Purpose: Several studies have reported a positive impact for taxanes in adjuvant breast cancer (BC) treatment in terms of reduced recurrence and mortality. However the impact of the magnitude on overall survival (OS) remains partially controversial. Methods: We examined the impact of taxane-containing adjuvant therapy for patients with early BC on OS, based on the number of deaths and on the calculated number of patients who need to be treated with taxanes to avoid one death (NNT). We classified patients in three different groups according to whether taxanes were administered concurrently or sequentially, and whether all treatment arms had the same or different duration. Results: 1) Taxanes in combination therapy: 8258 patients (4373 with taxanes and 3885 without taxanes), with 723 OS events. Overall survival for taxane-treated patients was 92.7% versus 89.6% for patients not receiving taxanes. NNT was 33. 2) Sequential treatment of unequal duration in the treatment arms: 14,228 patients (7970 with taxanes and 6256 without). Overall survival in taxane-treated patients was 86% compared with 83.2% for patients not receiving taxanes. NNT was 44. 3) Sequential treatment and similar duration in treatment arms: 9511 women (5093 with taxanes and 4418 without). Overall survival in patients treated with taxanes was 87% versus 85% in patients not receiving taxanes. NNT was 50. When the results of all these trials were considered together, the NNT stands at 43 patients. Conclusion: Taxanes afford a modest increase in overall survival in BC patients regardless of how they are given. Translational trials may well help to improve patient selection in the future.

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.

Adjuvant therapy for gastric cancer:What have we learned since INT0116?

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapsefree and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

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.