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INTRODUCTION: Completion of prescribed neoadjuvant chemotherapy (NACT) for breast cancer is paramount to patients obtaining full benefit from the treatment; however, factors affecting NACT completion are not known. We hypothesized that race is a predictor of completion of NACT in patients with breast cancer. METHODS: All patients with breast cancer treated with NACT from 2009-2016 at a single institution were stratified by completion of NACT and by race. Univariate analysis and multivariable logistic regression were used to identify patient and tumor characteristics which affected the rate of NACT completion. RESULTS: Ninety-two (74%) of 124 patients completed their prescribed NACT. On univariate analysis, white patients were more likely to complete NACT than non-white patients (76% vs 50%, p=0.006). Non-white patients were more likely to have government insurance and larger pre-chemotherapy tumors (both, p<0.05), but these factors were not associated with rates of NACT completion. After controlling for age, insurance status, tumor size, and estrogen receptor (ER) status, whites remained associated with completion of NACT (OR 3.65, p=0.014). CONCLUSION: At our institution, white patients with breast cancer were more likely than non-white patients to complete NACT. Further investigation into the underlying factors impacting this disparity is needed.

We are especially grateful to all the patients and their families who contributed the data that made this study possible. In addition, we thank the staff of the Clinical Research Unit of the Medical Oncology Service of the University Hospital of Jaen for their time and assistance, and the Fundacion MEDINA for their technical support. Lastly, we thank the Fundacion Bancaria Unicaja for the financial support. Jose Camacho is partly supported by the Agencia Andaluza del Conocimiento, Regional Government of Andalucia, in Spain, and ERDF (European Regional Development Fund) funds through project B-TIC-136-UGR20. ; Neoadjuvant chemotherapy (NACT) outcomes vary according to breast cancer (BC) subtype. Since pathologic complete response is one of the most important target endpoints of NACT, further investigation of NACT outcomes in BC is crucial. Thus, identifying sensitive and specific predictors of treatment response for each phenotype would enable early detection of chemoresistance and residual disease, decreasing exposures to ineffective therapies and enhancing overall survival rates. We used liquid chromatography high-resolution mass spectrometry (LC-HRMS)-based untargeted metabolomics to detect molecular changes in plasma of three different BC subtypes following the same NACT regimen, with the aim of searching for potential predictors of response. The metabolomics data set was analyzed by combining univariate and multivariate statistical strategies. By using ANOVA–simultaneous component analysis (ASCA), we were able to determine the prognostic value of potential biomarker candidates of response to NACT in the triple-negative (TN) subtype. Higher concentrations of docosahexaenoic acid and secondary bile acids were found at basal and presurgery samples, respectively, in the responders group. In addition, the glycohyocholic and glycodeoxycholic acids were able to classify TN patients according to response to treatment and overall survival with an area under the curve model > 0.77. In relation to luminal B (LB) and HER2+ subjects, it should be noted that significant differences were related to time and individual factors. Specifically, tryptophan was identified to be decreased over time in HER2+ patients, whereas LysoPE (22:6) appeared to be increased, but could not be associated with response to NACT. Therefore, the combination of untargeted-based metabolomics along with longitudinal statistical approaches may represent a very useful tool for the improvement of treatment and in administering a more personalized BC follow-up in the clinical practice. ; Fundacion MEDINA ; Fundacion Bancaria Unicaja ; Agencia Andaluza del Conocimiento, Regional Government of Andalucia ; European Commission B-TIC-136-UGR20

Purpose Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant chemotherapy. Methods Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant chemotherapy when indicated. Results The median follow-up duration was 28.9 months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The mean nodal ratio was 0.29 (range, 0-1.0; nodal ratio a parts per thousand currency sign0.25, 121 [59.0%] vs. > 0.25, 84 [41.0%]). Relapse free survival (RFS) of the patients who had a nodal ratio > 0.25 was significantly shorter (Hazard Ratio (HR) = 2.701, P = 0.001). A nodal ratio > 0.25 was also associated with a shorter overall survival (OS) (HR = 4.109, P = 0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P = 0.166, P = 0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR = 4.246, P < 0.001; HR = 7.764, P < 0.001). Conclusion Axillary nodal ratios have an independent prognostic value in stage II/III breast cancer treated with neoadjuvant chemotherapy. Nodal ratio might be a useful tool to identify the patients at high risk of relapse in the neoadjuvant setting. ; This study was supported by a Korean Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2006-531-E00034), a grant from the Seoul National University Hospital Research Fund (05-800- 20050148). ; N

The aim of this study was to evaluate the n-3 fatty acid supplementation effects in breast cancer patients. Methods: it was a prospective longitudinal study performed in breast cancer patients supplemented with fish oil during 8 weeks in neoadjuvant AC-T regimen. Anthropometric, Bioelectrical impedance (BIA) ((Lean Body Mass (LBM), and Phase Angle (PA)), food consumption, nutritional impact symptoms (NIS), metabolic and inflammatory profile were evaluated for 2 months. Results: supplemented patients presented weight gain of 1.4 kg, representing 1.8% of body weight. LBM was 42.3 Kg and PA 6.1º. Nausea, diarrhea and anorexia were the main NIS with reduction in incidence with the supplementation, but xerostomia and heartburn had increase. There was significant drop in hemoglobin values to 12.3 mg/dL, metabolic parameters and nutritional prognosis (CRP/albumin ratio) were not altered. Cytokines levels of TNF-? and interleukin-6 did not change, however interleukin-2 have shown significant increasing. Conclusion: Body weight gain was noticed in breast cancer patients, independent of food consumption. Fish oil supplementation during neoadjuvant chemotherapy was able to reduce NIS incidence, but not avoiding the decrease of hemoglobin levels, but it keeps the maintenance of pro-inflammatory parameters, except for increased the cytokine IL-2.

Background: Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients. Methods: Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR. Results: Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells. Conclusion: Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis. Copyright 2019 The Author(s). ; This work was supported by "Granada Research of Excellence Initiative on BioHealth (GREIB)", the PhD grant from the University of Granada and the PhD grant from the Spanish Government (FPU) 2014, REF FPU14/05461. ; https://dx.doi.org/10.1186/s13058-019-1109-0

Background: Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients. Methods: Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR. Results: Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells. Conclusion: Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis. ; This work was supported by "Granada Research of Excellence Initiative on BioHealth (GREIB)", the PhD grant from the University of Granada and the PhD grant from the Spanish Government (FPU) 2014, REF FPU14/05461

Abstract
The aim of the study was to evaluate the role of ultrasound guided fine needle aspiration cytology (FNAC) in the restaging of node positive breast cancer after neoadjuvant chemotherapy (NAC). From January 2016 – October 2018, 90 node positive stage IIA-IIIC breast cancer cases undergoing NAC were included in the study. The largest, most superficial and the most caudal axillary node metastasis confirmed by fine needle aspiration cytology (FNAC) was marked with clip. After NAC, restaging of axilla was performed with ultrasound and FNAC of the marked and/or the most suspicious axillary node. Of the 90 cases, 58 with available ultrasound guided percutaneous needle biopsy data were further evaluated. Axilla conserving surgery was performed in 37 of 58 cases and axillary lymph node dissection (ALND) in 21 of 58 cases. False Positive Rate (FPR) of FNAC after NAC was 12%, False Negative Rate (FNR) — 58%, sensitivity — 54%, specificity — 82%, accuracy 62%. FNAC after NAC had low FPR and was found to be useful in predicting residual axillary disease and to streamline surgical decision making regarding ALND. However, FNR was unacceptably high and FNAC alone was not able to predict ypCR and omission of further axillary surgery.

Xin Zhang,1,* Hejing Huang,2,* Ziran Wei,1,* Zhenxin Zhu,1 Dejun Yang,1 Hongbing Fu,1 Jiapeng Xu,1 Zunqi Hu,1 Yu Zhang,1 Qing You,1 Xin Huang,1 Ronglin Yan,1 Weimin Wang,1 Qingping Cai1 1Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Ultrasound, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China*These authors contributed equally to this workCorrespondence: Qingping Cai; Ronglin Yan Tel +86-21-81885601; +86-21-81885603Fax +86-21-81886000Email caiqingping@smmu.edu.cn; yanronglin@smmu.edu.cnBackground: What is the optimal neoadjuvant chemotherapy (NAC) regimen for locally advanced gastric cancer (LAGC) remains debatable. The objective of this study was to compare the efficacy of docetaxel+oxaliplatin+S-1 (DOS) vs oxaliplatin+S-1 (SOX) as NAC for LAGC.Methods: Data of 248 LAGC patients who received either DOS or SOX as NAC in our hospital between January 2010 and January 2018 were reviewed retrospectively. Propensity score matched (PSM) analysis was applied to minimize the selection bias in both groups. Prognostic factors were screened by univariate and multivariate Cox regression analyses.Results: Of the 248 LAGC patients included, 180 patients were subjected to the PSM analysis. Patients in DOS group showed a better tumor response to NAC, higher radical resection rate and R0 resection rate than those in SOX group. The overall survival (OS) rate in DOS group was better than that in SOX group, although the overall incidence of Grade 3/4 NAC-related toxicity in DOS group was higher, as represented by leukopenia and neutropenia. Multivariate analysis revealed that the NAC regimen, cTNM stage and the R0 resection rate were independent prognostic factors. In addition, patients with TLND less than 16 population showed a worse OS rate. Subgroup analysis indicated that patients benefited from the addition of docetaxel regardless of the clinical T stage, but those with high clinical N stages (N2-3) did not.Conclusion: DOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.Keywords: locally advanced gastric cancer, neoadjuvant chemotherapy, radical gastrectomy, propensity score matched analysis, docetaxel

OBJECTIVE: Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC. DESIGN: Transcriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025). CONCLUSION: The DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC. ; This work was supported by the Gastrointestinal Cancer Research Charitable Fund administered by the Belfast Health and Social Care Trust, the Cancer Research UK Experimental Cancer Medicine Centre Initiative, Invest Northern Ireland and Almac Diagnostics. Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) was funded by a programme grant from Cancer Research UK (RG66287). We would like to thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre from Addenbrooke's Hospital. Additional infrastructure support was provided from the CRUK funded Experimental Cancer Medicine Centre. RF has programmatic funding from the Medical Research Council and infrastructure support from the NIHR Biomedical Research Centre and the Cambridge Experimental Medicine Centre. Tissue samples used in this research were received from the Northern Ireland Biobank, which is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast Cancer Research UK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from the Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory has received funding from Cancer Research UK, the Friends of the Cancer Centre and the Sean Crummey Foundation. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no 721906. The OCCAMS Study Group is a multicentre UK collaboration.

Purpose: The aim of this study was to report the experience of Military Teaching Hospital Mohamed V (MTHM V) in the management of NPC treated with volumetric modulated arc therapy (VMAT) Materials and Methods: This is a retrospective study conducted between January 2013 and December 2017. All patients with a nasopharyngeal cancer were included. Patients who had distant metastasis at the time of diagnosis were excluded. The volumetric arc therapy modulation of intensity (VMAT) is the technique radiotherapy used in all our patients. Results: one hundred and one (101) patients with nasopharyngeal cancer were treated in our department. The average age was 42.95?16.36. The predominant histological type is undifferentiated carcinoma (UCNT) in 93 % of cases. Tumors were classified according to the American Joint Committee on Cancer (AJCC) classification of 2010 in Stage I : 1%, Stage II in 10.9%, Stage III in 45.5%, Stage IVa in 32.7% and stage IVb in 9.9%. The treatment consisted of neoadjuvant chemotherapy followedby concomitant radio chemotherapy (RCC) at 79.2 % of patients, an RCC immediately in 12.8 % of cases and 8 % of patients received neoadjuvant chemotherapy followed by exclusive radiotherapy. The therapeutic tolerance was good with 16.8% of acute radiomucite Grade 3, 8.9% of acute dermatitis Grade 3 and no complication Grade 4. The overall survival was 98.8% and 84.8% at 2 and 5 years respectively, and the PFS was 85.6% and 76.8% at 2 and 5 years, respectively. N3 and time to relapse were significant in multivariate analysis for OS. Neoadjuvant chemotherapy and N3 were significant in multivariate analysis for PFS. Conclusion: volumetric modulated arc therapy with concurrent chemoradiotherapy with additional neoadjuvant chemotherapy has good response and outcomes. Our findings are in good accordance with other series but further large studies are warranted to improve prognostic of this potentially curable malignancy.

BACKGROUND: This randomised, double-blind study compared pharmacokinetics, efficacy, safety and immunogenicity of PF-05280014 (potential trastuzumab biosimilar) and trastuzumab reference product (Herceptin) sourced from the European Union (trastuzumab-EU) as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: Patients (N = 226), stratified by primary tumour size and hormone receptor status, were randomised 1:1 to PF-05280014 or trastuzumab-EU (8 mg/kg loading dose; 6 mg/kg thereafter), each with docetaxel and carboplatin, every 3 weeks for six treatment cycles. Primary endpoint was percentage of patients with trough plasma concentration (C(trough)) >20 μg/ml at Cycle 5 (Cycle 6 predose). Efficacy endpoints included pathological complete response and objective response rate. Non-inferiority of PF-05280014 to trastuzumab-EU was declared if the lower limit of the 95% confidence interval for the stratified difference between groups in the percentage of patients with Cycle 5 C(trough) >20 μg/ml was above the prespecified non-inferiority margin of – 12.5%. RESULTS: For PF-05280014 vs trastuzumab-EU patients, respectively, 92.1% vs 93.3% had Cycle 5 C(trough) >20 μg/ml; the lower limit of the 95% confidence interval (− 8.02%, 6.49%) for the stratified difference between groups was above the non-inferiority margin (– 12.5%). Pathological complete response (47.0% vs 50.0%) and central radiology review-assessed objective response (88.1% vs 82.0%) rates were comparable. Incidence of all-causality, grade 3–4 treatment-emergent adverse events was 38.1% vs 45.5%; antidrug antibody rates were 0% vs 0.89%. CONCLUSIONS: PF-05280014 demonstrated non-inferior pharmacokinetics and comparable efficacy, safety and immunogenicity to trastuzumab-EU in patients with operable HER2-positive breast cancer receiving neoadjuvant chemotherapy.

PURPOSE: Time to surgery (TTS) is a potentially modifiable factor associated with survival after breast cancer diagnosis and can serve as a proxy for quality of oncologic care coordination. We sought to determine whether factors associated with delays in TTS vary between patients who receive neoadjuvant systemic therapy (NST) vs upfront surgery and whether the impact of these delays on overall survival (OS) varies with treatment sequence. METHODS: Women ≥18 years old with Stage I-III breast cancer were identified in the National Cancer Database (2004–2014). Multivariate linear regression stratified by treatment sequence (upfront-surgery vs NST [neoadjuvant chemotherapy {NAC}, neoadjuvant endocrine therapy {NAE}, or both {NACE}]) was used to identify factors associated with TTS. Cox proportional hazards models were used to estimate the effect of TTS on overall survival (OS). RESULTS: Of 693,469 patients, 14.8% (n=102,326) received NST (NAC n=85,143, NAE n=10,004, NACE n=7179). Non-White race/ethnicity, no or government-issued insurance, more extensive surgery (i.e., mastectomy and contralateral prophylactic mastectomy vs breast-conserving surgery), and post-mastectomy reconstruction were associated with significantly longer adjusted TTS for NAC and upfront-surgery recipients, but only upfront-surgery patients had progressively worse OS with increasing TTS (>180 vs ≤30 days: HR=1.31, all p<0.001). CONCLUSIONS: Surgery extent, race/ethnicity, and insurance were associated with TTS across treatment groups, but longer TTS was only associated with worse OS in upfront-surgery patients. Our findings can help inform surgeon-patient communication, shared decision-making, care coordination, and patients' expectations throughout both NST and in the perioperative period.

This study is being supported by grant no 04-2012-0290 from the SNUH Research fund and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP)(No. 2013005540). Letrozole and metformin are being supplied by the pharmaceutical company, Shin Poong Pharm. Co., Ltd. ; Background : Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design : Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion : This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration : ClinicalTrials.gov Identifier NCT01589367 ; Peer Reviewed