scholarly journals Injectable hydrogels for the sustained delivery of a HER2-targeted antibody for preventing local relapse of HER2+ breast cancer after breast-conserving surgery

Theranostics ◽  
2019 ◽  
Vol 9 (21) ◽  
pp. 6080-6098 ◽  
Author(s):  
Xiaobin Chen ◽  
Maoli Wang ◽  
Xiaowei Yang ◽  
Yaoben Wang ◽  
Lin Yu ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 902
Author(s):  
Florence Lerebours ◽  
Luc Cabel ◽  
Jean-Yves Pierga

Endocrine therapy is the mainstay of treatment in HR+/HER2- breast cancers, which represent about 70% of all breast cancers. Neoadjuvant therapy has been developed since the 1990s to address several issues, including breast-conserving surgery (BCS) and improvement of survival rates. For a long time, neoadjuvant endocrine therapy (NET) was confined to frail patients in order to improve surgery outcome. Since the 2000s, NET now plays a central role as a research tool for predictive endocrine sensitivity biomarkers and targeted therapies. One of the major issues in early HR+/HER2- breast cancer is to identify patients in whom chemotherapy can be safely withheld. In vivo assessment of response to NET might be the best treatment strategy to address this issue.


2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 147-147
Author(s):  
Kerry Lynn Reynolds ◽  
XingXing Cheng ◽  
Ashmeet Bhatia ◽  
Michelle Connolly Specht ◽  
Barbara Lynn Smith ◽  
...  

147 Background: Dual neoadjuvant HER2 directed therapy is offered only in a clinical trial setting and is not standard of care, but emerging data suggests targeting multiple mechanisms may be more effective. We conducted a comprehensive systematic review and meta-analysis to evaluate the impact of neoadjuvant dual and single agent HER2 blockade on breast conserving surgery (BCS), and on pathological complete response (pCR) for estrogen receptor (ER)+ and ER- tumors, as well as the impact of pCR on disease-free survival (DFS) and overall survival (OS) for HER2+ breast cancer. Methods: MEDLINE, EMBASE, and Cochrane Controlled Clinical Trials Register databases were queried to identify eligible trials. Inclusion criteria were prospective, neoadjuvant trials that had at least one arm with HER2 directed therapy, and reported pCR. Pooled relative risk ratios (RRs) and p values were estimated for endpoints using the random effects statistical model. Results: We identified 36 trials (N = 4130). High pCR rates (> 40%) were seen with anthracycline-based chemotherapy and trastuzumab alone, and non-anthracycline based dual HER2 blockade. The addition of trastuzumab to chemotherapy did not improve BCS rate (RR 1.40, p = 0.15), but significantly increased rates of pCR (RR 1.91, p = 0.0001). Similarly, dual HER2 blockade compared to trastuzumab alone did not improve BCS rate (RR 1.03, p = 0.84), but significantly increased rates of pCR overall (RR 1.39, p < 0.00001), in both ER+ (RR 1.72, p = 0.01) and ER- subsets (RR 1.91, p = 0.0001), with no increase in grade 3/4 toxicity (RR:1.13, p = 0.16). Dual HER-2 blockade without chemotherapy was associated with pCR in a subset (11.2% - 27%) with minimal toxicity (incidence of grade 3/4 toxicity:1-5%). Higher pCR was associated with improved DFS (RR 2.29, p = 0.006) and OS (RR 4.61, p = 0.009). Conclusions: Neither the addition of trastuzumab to chemotherapy, nor the dual-HER2 blockade compared to trastuzumab, improves rates of BCS. However,both significantly improve rates of pCR, which is associated with improved DFS and OS. Dual HER2 blockade,with endocrine therapy for ER+, could potentially lessen or even obviate the use of chemotherapy.


2021 ◽  
Vol 27 ◽  
Author(s):  
Katalin Boér ◽  
Zsuzsanna Kahán ◽  
László Landherr ◽  
Tibor Csőszi ◽  
Károly Máhr ◽  
...  

Purpose: The neoadjuvant use of pertuzumab and trastuzumab with chemotherapy improves the pathologic complete response (pCR) in early HER2+ breast cancer. The aim of this study was to determine the pCR rate obtained with dual HER2 blockade in routine clinical practice. The secondary and tertiary objective was to investigate the impact of neoadjuvant systemic therapy (NST) on performing breast-conserving surgery and survival data.Methods: This was a multicentre, retrospective, observational study in patients with stage II and III HER2+ early breast cancer who received pertuzumab and trastuzumab-based NST. Data were collected from patients’ medical records.Results: Eighty-two patients were included in the study treated in 8 cancer centers in Hungary between March 2015 and January 2020. The study included women with a median age of 50.3 years. The majority of the patients (95%) received a sequence of anthracycline-based chemotherapy followed by docetaxel. pCR was achieved in 54% of the cases. As a result of NST a significant increase of conservative breast surgeries (33% vs. 3.6% planned, p = 0.0001) was observed. Ki67 expression and neutrophil-to-lymphocyte ratio (NLR) significantly predicted pCR. None of the variables were independent predictors of DFS.Conclusion: The pCR rate achieved in our study demonstrates the reproducibility of trial data in a real-world population. The rate of breast-conserving surgery was significantly increased.


2021 ◽  
Vol 12 (1) ◽  
pp. 30-38
Author(s):  
A. D. Zikiryahodjaev ◽  
M. V. Ermoshchenkova ◽  
A. R. Bosieva ◽  
J. F. Omarova ◽  
N. N. Volchenko ◽  
...  

Aim. To determine the frequency of local recurrence of breast cancer (BC) after performing breast-conserving surgery (BCS) during and after complex treatment, to study the risk factors for local recurrence and survival.Materials and methods. A retrospective cohort study of 675 patients with breast cancer who underwent BCS followed by remote radiotherapy was conducted. The frequency of local relapse and risk factors were studied, 3- and 5-year local-free survival. The odds ratios (OR) and 95% confidence intervals (CI) were calculated, and the Kaplan–Meyer curves were constructed.Results. Radical breast resections (RBR) were performed in 46.7% of patients, and oncoplastic breast resections (OBS) in 53.3% of patients. The most common histological type in both groups was invasive cancer with no signs of specificity: 76.9% and 84.1% – in the OBS and RBR groups, respectively. The incidence of cancer in situ was higher in the OBS group: 14.7% vs. 3.3% in the RBR group (p < 0.001), metastases in regional lymph nodes were more frequent in the RBR group: 34.3% against 20.3% in OBS (p < 0.001). According to the immunohistochemical type and degree of differentiation, the groups did not differ. For 3 years, the relapse-free survival rate was 99.7% in both groups, and for 5 years – 99.2% in the OBS group. and 99.7% in the RBR group, 6 years – 98.3% and 98.7%, respectively; no significant differences were found between the groups. There were no statistically significant differences in the frequency of relapses depending on the width of the resection edges from <1 to ≥10 mm. The risk of relapse was increased with a preserved menstrual status (OR 20.05; 95% CI 2.52–159.33), Her2/neu–positive (OR 5.11; 95% CI 1.04–25.09) and triple-negative types (OR 4.02; 95% CI 1.02–15.95), the degree of differentiation of G3 (OR 5.58; 95% CI 1.59–19.64).Conclusion. BCS is characterized by oncological safety; the rate of local relapse within 6 years is 1.5%. Risk factors for relapse include active menstrual status, highly aggressive immunohistochemical types of breast cancer, and low degree of differentiation.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 571-571
Author(s):  
Neil Chandrabhan Chevli ◽  
Waqar Haque ◽  
Kevin Thomas Tran ◽  
Andrew M. Farach ◽  
Mary R. Schwartz ◽  
...  

571 Background: Based on the results of the CALGB 9343 trial, patients age ≥70 with T1N0 ER/PR+ HER2- breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). This trial predated the 21- gene RT-PCR recurrence score (RS) test, which is an assay now available for patients with hormone receptor positive, HER2 negative, node negative breast cancer to determine who will benefit from chemotherapy. Whether the RS can predict for patients most likely to benefit from radiation therapy (RT) following BCS has not been previously examined. The purpose of this study was to use a large database of patients age ≥70 with T1N0 ER/PR+ HER2- disease to determine if RS could predict who would benefit from RT following BCS. Methods: The National Cancer Database (NCDB) was queried (2004-2017) for female patients age ≥70 with pT1N0 ER+ PR+ HER2- breast cancer treated with BCS and ET and who had an available RS. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). For survival analysis, propensity score matching (PSM) was conducted overall and for each group to create 1:1 matched cohorts of patients who received radiotherapy and patients who did not. Kaplan-Meier analysis with log-rank testing was used to evaluate overall survival (OS). Univariable (UVA) and multivariable (MVA) analysis were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for OS. Results: A total of 13,614 patients met the selection criteria: 3,840 in the LR cohort, 8,383 in the IR cohort, and 1,391 in the HR cohort. A total of 79% received RT: 77% in the LR cohort, 79% in the IR cohort, and 85% in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, overall the 5-year OS was 90% for those who received RT and 88% for those who did not (p = 0.03). The 5-year OS in the LR cohort was 89% for those who received RT and 89% for those who did not (p = 0.517). In the IRHR cohort, the 5-year OS was 93% for those who received RT and 88% for those who did not (p = 0.004). On MVA in the overall cohort, RT (p = 0.037) was predictive of improved OS while increasing age (p < 0.001) and CDCC comorbidity score (p < 0.001) were predictive of worse OS. On MVA in the LR cohort, RT (p = 0.602) was not predictive of improved OS. However, on MVA in the IRHR cohort, RT (p = 0.004) was a positive prognostic factor for OS. Conclusions: This is the first study investigating the role of RS in this subset of patients eligible for omission of radiotherapy. There is an OS benefit with the use of RT in patients with IRHR RS, but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.


2020 ◽  
Vol 99 (11) ◽  

Introduction: The aim of this pilot retrospective study is to evaluate the complication rate in patients after axillary dissection comparing preparation with harmonic scalpel vs traditional ligation technique, and to analyse risk factors for complications occurrence. Methods: 144 patients with 148 axillary dissections operated in a single centre between January 2014 and 2019 were included into the study. Axillary dissection was performed using harmonic scalpel in 73 and absorbable ligations in 70 cases. Results: Seroma formation was observed in 41 patients (56.2%) in the harmonic scalpel group and in 21 patients (30.0%) in the ligations group (p=0.003). The mean period from the surgery to drain removal was 4.0 days in the harmonic scalpel group and 3.0 days in the ligations group (p<0.001). The mean amount of the drained fluid after mastectomy was 300.9 ml in the harmonic scalpel group and 168.7 ml in the ligations group (p=0.005); after breast conserving surgery, it was 241.9 ml and 107.4 ml, respectively (p =0.023). Conclusion: In comparison with traditional ligations with absorbable material, axillary dissection using harmonic scalpel significantly increases the risk of postoperative seroma formation, prolongs the time from the surgery to drain removal, and increases the amount of drained fluid.ut any suspicion of nodal involvement, hemithyroidectomy is considered to be a sufficient procedure or the method of choice, respectively.


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