bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of discordance in estrogen receptor, progesterone receptor, and Ki-67 after neoadjuvant chemotherapy in breast cancer on survival.
Authors: Ding Yu-Qin , Ding Xiaowen , Ding Kaijing , Cao Wen-Ming , Zou Dehong , Yang Hongjian , Zhang Fanrong , He Xiangming , Mo Wenju , Qin Chengdong , Zheng Yurong 
Published: May 2019

e12079 Background: The expression status of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 antigen (Ki-67) divides breast cancer into different subtypes. Changes in these biomarkers during treatment alter the overall treatment decision and affect prognosis. To date, few studies have investigated the effects of changes in these biomarkers throughout neoadjuvant chemotherapy (NAC) on patient prognosis. Methods: A total of 482 patients who received NAC were enrolled. The expression of ER, PR and Ki-67 between pre- and posttherapy specimens was studied by immunohistochemical methods. Physical and imaging examinations based on the Response Evaluation Criteria in Solid Tumors guidelines version 1.1 were utilized to assess the treatment response. The impact of these biomarkers status changes on survival was then tested for statistical significance using a Cox proportional hazards regression model for univariate and multivariate analyses. Results: The rate of discordance for ER, PR and Ki-67 was 10.37%, 17.01% and 77.39%, respectively, in which the PR positive-to-negative conversion was the most common change. A statistically significant differential overall survival (OS) related to biomarkers status throughout NAC (P<.01) was noted. The risk of death in patients with a PR positive-to-negative conversion was 6.58 times greater than that of stable PR expression (P=.002). The risk of disease recurrence in patients with increased Ki-67 expression was 1.91 times greater than that of stable Ki-67 expression (P=.02). Furthermore, we validated both of them as independent predictors of poor prognosis. Conclusions: We concluded that inconsistent expression of biomarkers can significantly affect patient prognosis. We suggest that biomarkers investigations during NAC may potentially improve patient management and survival. Survival result that compared with concordance and discondance in ER, PR and Ki-67. (N=482).*P<.05. [Table: see text]
Outcomes of Hispanic/Latino women with triple-negative breast cancer who achieve a complete pathologic response after neoadjuvant chemotherapy.
Authors: Philipovskiy Alexander , Corral Javier Chavez , Heydarian Rosalinda , Dwivedi Alok Kumar , Xiaoming Gong , Leelani Sajid , Gaur Sumit 
Published: May 2019

e12081 Background: The aim of this study was to determine the efficacy of neoadjuvant chemotherapy (NACT) versus adjuvant chemotherapy (ACT) in Hispanic/Latino (H/L) women with triple negative breast cancer (TNBC). Methods: We retrospectively reviewed 104 records of female patients diagnosed with TNBC, stages I–III, treated at Texas Tech Breast Care Center from 2006 to 2016. Pathological complete response (pCR), overall survival (OS) and progression-free survival (PFS) were estimated and compared between two treatment groups. Kaplan Meier survival curve and Cox proportional hazards regression analyses were conducted to determine unadjusted and adjusted effects of NACT compared to ACT. Results: Of 104 TNBC patients with median duration of follow up of 6 (range 2-11) years, 30 (29%) received NACT and 74 (71%) received ACT. Women undergoing NACT were mostly younger, with a mean age of 50.8 (range 40-67) years, compared with those in the ACT group, mean age of 53 (range 32-80) years. Additionally, women in the NACT group had more advanced cancer, stage III (61%) and stage II (33%), in contrast to the ACT group, who had stage III (23%) and stage II (55%). Of 30 patients received NACT,twelve (40%) had pCR. The (median 6 years/range 2-11 years Women who achieved pCR had better PFS and OS compared with patients who received ACT. On the other hand, women with residual cancer after NACT had worse survival outcomes compared with women who received ACT (Hazards Ratio-HR = 0.1, p = 0.001). Conclusions: In our study, we observed that the patients in the NACT group with residual cancer had statistically significantly worse survival outcomes compared with ACT group. Patients who received NACT and had pCR had no relapse over the observation period. Our study suggests that there is a need of a prospective study to better understand the biology of TNBC among H/L women in order to individualized NACT to population of patients with “chemosensitive” subtype of TNBC.
Quality of life after preoperative radio-/chemotherapy in locally advanced breast cancer patients.
Authors: Matuschek Christiane , Nestle-Kraemling Carolin , Wollandt Sylvia , Speer Vanessa , Boelke Edwin , Roth Stephan L. , Audretsch Werner , Tamaskovics Balint , Lammering Guido , DjiepmoNjanang Freddy Joel , Budach Wilfried , Haussmann Jan 
Published: May 2019

e12083 Background: Preoperative radiotherapy and chemoradiotherapy (PRT/PCRT) represents an increasingly used clinical strategy in different tumor sites. However, concerns regarding a possible unfavorable influence on the clinical outcome still exist. The aim of the current study was to examine the long-term global health status in our series of LABC patients treated with PRT/PCRT followed by breast-conserving surgery (BCS) or mastectomy (ME). Methods: Of the 315 patients treated with PRT/PCRT in the years 1991 and 1999, 203 patients were still alive at long-term follow up of mean 17.7 years (range 14-21). Thirty-seven patients were lost to follow up and 58 patients refused to be contacted, which resulted in 107 patients (64 patients after BCS and 43 after mastectomy) being available and willing to undergo further clinical assessment. PRT/PCRT consisted of external beam radiation therapy (EBRT) with 50 Gy (5 × 2 Gy/week) to the breast and the supra-/ infraclavicular lymph nodes combined with a consecutive electron boost or (in case of BCS) a 10-Gy interstitial brachytherapy boost with Ir-192 prior to EBRT. Overall, chemotherapy was administered either prior to RT or concomitantly in the majority of patients. Quality of life (QoL) was assessed by EORTC QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. Results are reported using functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and symptom-related items (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). The results were compared to a published reference cohort of n=2028 healthy adults (16-92 years), including n=1139 women (age 16-92 years). EORTC QLQ-C30 functional scales were also analyzed between different subgroups including an age-matched analysis with a two sided paired t-test. Results: In comparison with this healthy control group of 1139 women, we did not detect any significant differences for the functional scales measured by physical function, emotional well-being, cognitive, and social function as well as the symptom scales: fatigue, nausea, vomiting, pain, diarrhea and financial difficulties for both groups. However, significant inferior scores were found in the present study group regarding obstipation (p=0.013), loss of appetite (0.038), sleeping disorder (p=0.01) and dyspnoe (p=0.01). Conclusions: Taken together, retrospective as well as prospective data underline the feasibility of preoperative radiotherapy in breast cancer.
Nomogram for predicting axillary lymph node pathological complete response in node-positive breast cancer patients after neoadjuvant chemotherapy.
Authors: Wang Wenyan , Wang Xin , Wang Xiang , Liu Jiaqi , Zhang Pin 
Published: May 2019

e12090 Background: Pathological complete response (pCR) of axillary lymph nodes (ALNs) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC), and ALN status is an important prognostic factor for breast cancer patients. Our goal is to develop a new predictive clinical model to assess the axillary lymph node pCR rate after NAC. Methods: A retrospective series of 547 patients who had biopsy-proven positive ALNs at diagnosis and undergoing axillary lymph node dissection from 2007 to 2014 in National Cancer Center/Cancer Hospital of Chinese Academy of Medical Sciences. We analyzed the clinicopathologic features and developed a nomogram to predict the probability of ALN pCR. Univariate assessment was performed using a logistic regression model. A multivariate logistic regression stepwise model was used to generate a nomogram to predict ALN pCR in node positive patients Variables with P < 0.05 on multivariable analysis were included in the nomogram. The adjusted area under the receiver operating characteristic curve (AUC) was calculated to quantify the ability to rank patients by risk. Internal validation was estimated using 50-50 hold out validation method. Nomogram was validated externally with the prospective cohort of 167 patients from 2016 to 2018. Results: In retrospective study, there were 172 (31.4%) patients achieved axillary pCR after NAC. Multivariate analysis indicated that clinical nodal (N) stage, hormone receptor (HR) status and clinical response of primary tumor after NAC were significant independent predictors for axillary pCR ( P< 0.05). The NAC nomogram was based on these three variables. In the internal validation of performance, the AUCs for the training and test sets were 0.719 and 0.753, respectively. The nomogram was validated in an external cohort with an AUC of 0.734. Conclusions: We developed a nomogram to predict the likelihood of axillary pCR in node positive breast cancer patients after NAC. The predictive model performed well in prospective external validation. This practical tool could provide information to surgeons regarding whether to perform additional ALND after NAC.
Pathological complete response rate (pCR) in thirty-three women with triple-negative breast cancer (TNBC) treated with a neoadjuvant carboplatin-based regimen.
Authors: Chopra Avani , Wojtowicz Mark , Manikowski Jesse , Maddineni Bhumika , Kirchner Lester , Panikkar Rajiv Prasanna , Vogel Victor G. 
Published: May 2019

e12099 Background: The purpose of this retrospective case series was to assess pCR rate, progression-free survival and prognostic factors in TNBC. Methods: We reviewed medical records for 33 consecutive female patients with TNBC (41% node+) treated between July 2015 and April 2018 with neoadjuvant paclitaxel 80 mg/m2 IV weekly plus concurrent carboplatin (AUC 4) every 3 weeks for a total of 12 weeks followed by dose-dense doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 2 weeks for a total of 4 cycles. Surgical pathology was studied to determine the presence or absence of residual disease at surgery. Age at treatment, tumor stage, subsequent hospitalizations, and genetic testing were recorded. Patients with residual disease were treated with adjuvant capecitabine 1500 mg PO BID, one week on, one week off, for 6 monthly cycles ± radiation; some patients with a complete pathological response also received postoperative radiation. Results: Among 33 patients, 17 patients had pCR (52%, median age 58 yrs), 10 had a partial response and 6 had no response or progression (median age 63.5). After surgery 24 patients received radiation therapy (XRT). There were 6 hospitalizations, 3 that were treatment related, 2 for neutropenic fever and one for renal failure induced by carboplatin; all 3 resulted in chemotherapy dose reductions; all 3 had pCR. 3 progressions/recurrences were recorded: 2 after treatment and 1 progression during treatment. Two deaths occurred, 1 secondary to progressive disease. Median progression free survival time was 8.5 months (range 0.1 to 24.0 mos). Median time since diagnosis is 16.7 months (range 8.1 to 37.6 mos). There was no significant difference in the median age of patients who had a pCR compared with patients with residual disease. Conclusions: We observed pCR in patients with TNBC treated with a pre-operative carboplatin-containing regimen (superior to historical pCR rates in patients receiving taxanes and anthracyclines only). Although there are insufficient data to demonstrate increased overall survival, we show an improvement in prognosis with a carboplatin-containing regimen for TNBC.
Sequence of anthracyclines and taxanes in the neoadjuvant chemotherapy of HER2-negative breast cancer: Experience of a Brazilian oncological center.
Authors: Preto Daniel D’Almeida , Sanches André Octavio Nicolau , Barroso Alison Wagner Azevedo , Carbinatto Alessandra Caroline Moretto , Veneziani Ana Lima , Kons Georgia , BUDIB MARIA , Safro Maria Augusta Zaffari , Pinto Gustavo Sanches Faria , Bello Secco Alan Felipe , Zorzetto Marina Moreira Costa , Lacerda Domicio , Paiva Carlos Eduardo , Souza Cristiano de Pádua 
Published: May 2019

e12105 Background: The best sequence of anthracyclines and taxanes in the neoadjuvant chemotherapy of HER2-negative breast cancer is still unknown. The aims of this study were to assess the impact of the sequence order in the pathological complete response (pCR) rate, and in the disease free survival (DFS) and overall survival (OS). Methods: We retrospectively reviewed 235 HER2-negative breast cancer women treated with neoadjuvant chemotherapy from 2003 to 2011 at our cancer center. The patients were pooled in two groups: anthracycline-based followed by taxanes (AC-T) and the reverse sequence (T-AC). The chi-square test was performed to verify the homogeneity between the groups and to compare pCR rate among the treatment groups. Cumulative survival probabilities were calculated using the Kaplan-Meier method. Differences between survivals were tested using the log-rank test. Results: The AC-T (n = 161) and T-AC (n = 74) groups were balanced for age, staging, receptor profile and histologic grade. The follow-up was at least five years for each patient. The median age was 50.1 years. Most patients (97%) had stage III tumors and 72 (30%) had triple negative disease. pCR rate was higher in triple negative compared with luminal cases (16.3 vs. 7.3%; p = 0.049). Treatment sequence did not influence the occurrence of pCR (10.5 vs. 8.5%; p = 0.8) or median survival times (DFS: 87.9 vs. 64.1, p = 0.85; OS: 91.1 vs. 71.6 months, p = 0.15), in the AC-T and T-AC groups, respectively. Conclusions: The sequence of neoadjuvant taxane-anthracycline-based chemotherapy regimen in daily practice did not show difference in the evaluated clinical outcomes. The retrospective design and the low number of patients may limit the power of the study to detect statistically significant differences. Phase III trials should be stimulated in this context. [Table: see text]
Genomic profiling of residual tumor after neoadjuvant chemotherapy for breast cancer.
Authors: Hattori Masaya , Rajagopal Padma Sheila , Sveen Lise , Khramtsova Galina , Yoshimatsu Toshio , Beaubier Nike , Barber Mathew , Abboushi Taylor , Fang Liu , Zheng Yonglan , White Kevin , Huo Dezheng , Olopade Olufunmilayo I. 
Published: May 2019

e12106 Background: Patients who have residual disease after neoadjuvant chemotherapy (NAC) have a higher risk of metastatic recurrence. Residual disease likely includes therapy-resistant subclones of breast cancer cells, which untreated lead to metastases. The aim of this study was to identify additional adjuvant therapies based on genomic profiling of residual disease post NAC therapy. Methods: Next-generation sequencing of tumor samples from patients (pts) with residual invasive breast cancer after NAC was performed using a Tempus xT, 595 gene panel on matched tumor-normal samples. All samples were obtained from the University of Chicago Breast Cancer tissue bank. Clinical information was obtained from electronic health records and the cancer registry. Results: Of 23 evaluable patients enriched for African Americans, 65% were HER2-positive, 22% TNBC and 13% ER+/HER2-. At a median follow up of 2.9 years, 8 pts (35%) have recurred and 8 were dead. We identified 119 clinically actionable variants in 22 tumors, and the most commonly altered genes were TP53 (18 alterations, 74% of cases), ERBB2 (8, 26%), PIK3CA (7, 30%), CDK4 (4, 17%), MCL1 (4, 17%), and MDM2 (4, 17%). Of significance, 67% of HER2-positive pts had no detectable ERBB2 copy number gain in the residual tumor. 78% of pts had at least one potential druggable target according to CIViC and/or OncoKB: 19 variants in HER2-positive, 8 in HER2-negative. The mean estimated tumor mutation burden (TMB) was 4.34 m/MB (range: 0-26.7), and 13% were considered TMB-high ( > 9 m/MB). No patients had high-microsatellite instability type residual tumors. Conclusions: Many potentially targetable alterations reside in residual disease of both HER2-positive and -negative breast cancer after NAC. Post-NAC treatment targeting these harbored alterations and post-NAC immunotherapy could have impact on the prognosis of breast cancer patients who have residual disease after NAC. [Table: see text]
FDG uptake to reflect NLR and expression levels of TILs and PD-L1 in patients with primary breast cancer: Tumor inflammation and immunity.
Authors: Fujii Takaaki , Hirakata Tomoko , Kurozumi Sasagu , Katayama Ayaka , Yanai Keiko , Tokuda Naoko , Nakazawa Yuko , Obayashi Sayaka , Yajima Reina 
Published: May 2019

e12110 Background: 18F-Fluorodeoxyglucose-positron emission tomography(FDG-PET) is used to evaluate the glucose metabolic rates of cancers. Several studies have reported that high FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer (BC).However, FDG-uptake is influenced by many factors, including inflammation and immunity. In this study, we investigated the relationship between FDG uptake and inflammation and immunological factors, including Neutrophil/lymphocyte ratio (NLR) and degrees of Tumor-infiltrating lymphocytes (TILs), programmed cell death ligand 1 (PD-L1). Methods: We retrospectively investigated the cases of 96 consecutive invasive ductal carcinoma patients who underwent surgery andunderwent FDG-PET preoperatively. The evaluation of PET was determined using standardized uptake value max (SUVmax). We divided the cases into two groups based on the value of SUVmax; low (<2.5) and high (≥2.5) and the value of NRL; low (<1.7) and high (≥1.7). Grade of stromal-TILs was immunohistochemically (IHC) evaluated using the criteria of the International Working Group for TILs in BC: low (10-20%), intermediate (20-40%) and high (50-90%). PD-L1 positive were evaluated by IHC. The relationships between SUVmax and NLR and expressions of TILs, PD-L1 were investigated. Results: Among the 96 patients, 52 (54.2%) had high SUVmax in the primary tumor. The multivariate analysis revealed that large tumor size (p<0.001), high nuclear grade (p=0.016), high NLR (p=0.037), and PD-L1 (p=0.003) were significantly associated with high SUVmax in the primary tumor.There were associations between SUVmax and NLR(r=0.319, p<0.001) and TILs (r=0.298, p<0.001). Among the 96 cases with, there was 4 cases (4.2%) had recurrent disease, while 3 cases among the 4 cases with recurrent disease was low TILs and the one case was high TILs and PD-L1 psitive. disease recurrence.It is interesting to note that the group with high SUVmax and low NLR had no recurrent disease. Conclusions: The present study demonstrated thatthe finding of preoperative FDG uptake in BC may be reflective of poor prognosis and high NLR and the grades of high TILs and expression of PD-L1in the tumor. From these findings, preoperative high FDG uptake in BC may be reflective of tumor microenvironmentincluding inflammatory or immunological features in addition to aggressive features among patients with BC.
Circulating cell-free DNA (ctDNA) assessments before, during, and after neoadjuvant therapy (NAC) in nonmetastatic inflammatory breast cancer (IBC).
Authors: Hall Carolyn S. , Meas Salyna , Sarli Vanessa Nicole , Lucci Anthony 
Published: May 2019

e12113 Background: : IBC is a rare and aggressive subtype of breast cancer. A significant number of IBC patients who achieve pathologic complete response (no residual tumor in breast and axillary nodes, pCR) relapse after NAC. We hypothesized that circulating cell-free DNA (ctDNA) identified in blood before, during, and after NAC would identify novel ctDNA targets. Methods: Plasma ctDNA was extracted from 43 non-metastatic IBC patients (IRB: LAB04-0698) pre, mid, and post-NAC. The Oncomine Pan Cancer ctDNA Assay (ThermoFisher) was used for library preparation, and high throughput next generation sequencing was performed on a GeneStudio S5XL System (ThermoFisher), following manufacturer’s directions. ThermoFisher Ion Reporter 5.10 Software was used to analyze single nucleotide variants (SNVs), and copy number variants (CNVs). Results: Seventeen patients had pre-NAC ctDNA assessments; 7/17 (41%) had PIK3CA SNVs; 5/7 also had MYC or FGFR2 CNVs. Five of 17 (29%) had TP53 SNVs; 2/5 also had FGFR2 CNVs. Ten patients had mid-NAC ctDNA assessments; 9/10 (90%) had PIK3CA SNVs; 5/9 also had FGFR2 CNVs, 2/9 had FGFR2 and FGFR3 CNVs, 2/9 also had TP53 SNVs, 1/9 had FGFR2 and ERB2 CNVs. Thirty-one patients had post-NAC ctDNA assessments; 5/31 (16%) had PIK3CA SNVs; 2/5 had FGFR2 CNVs, 1/5 also had a TP53 mutation and an FGFR2 CNV, 1/5 had FGFR2 CNV, and FGFR3 CNV. Six of 31 (19%) had TP53 SNVs, 1/6 had CCND1 CNVs, no CNVs were detected in 6 patients with TP53 SNVs. Six of 31 (19%) had MAP2K1 SNVs. Three of 31 (10%) had MET SNVs; 1/3 had CCND3 CNVs, no CNVs were detected in 2 patients with MET SNVs. No SNVs or CNVs were detected in 10/31 (32%) of patients post NAC. Conclusions: ctDNA assessments before, during, and after NAC identified novel targets that could be tested in future adjuvant therapies trials in IBC patients who remain at high risk for relapse.
Efficacy and safety of intensified platinum-based neoadjuvant chemotherapy in locally advanced triple-negative breast cancer: Preliminary results of non-randomized phase II study.
Authors: Glazkova Elena , Frolova Mona , Stenina Marina , Ignatova Ekaterina , Rumyantsev Alexey , Petrovsky Alexander , Krohina Olga , Tjulandin Sergei 
Published: May 2019

e12116 Background: patients with locally-advanced triple negative breast cancer (TNBC) have dismal prognosis with current standard of care therapy. Pathologic complete response (pCR) is the most important prognostic factor for long-term survival of these patients. Methods: this was non-randomized prospective single-center phase II study. Key inclusion criteria were histologically verified locally advanced TNBC, non-eligibility for primary surgical treatment (ie, TNM stage Т2-4N 2-3M0) and no evidence of metastatic disease. Patients were treated with 8 cycles of neoadjuvant doxorubicine, paclitaxel and cisplatin chemotherapy (ATP; doxorubicine 40 mg/m2 day 1, paclitaxel 160 mg/m2 day 1 and cisplatin 50 mg/m2 day 1 every two weeks) with G-CSF support (filgrastim 5 mcg/kg day 2-6). After 8 cycles of chemotherapy patients were referred for surgical treatment; adjuvant radiation therapy was prescribed to all patients. Primary end point was pCR assessed in modified intention-to-treat population (ie, in patients who underwent surgical treatment). Key secondary endpoints were disease-free survival (DFS) and pCR rate according to BRCA status. Results: we enrolled 80 patients, 79 (98.7%) of them underwent surgical treatment and were included in the analysis. Median age was 46 years (25-68), 22 (27.1%) patients had BRCA1 mutations, 5382insC was the most common mutation (17 [77.2%] of patients); 1 (1.2%) patient had CHEK2 mutation. pCR was achieved in 51 (64.5%) patients. In with BRCA1-mutation carriers pCR rate was 61.9%, in patients with 5382insC – 81.2%. 2-year DFS was 77.3%; 2-year overall survival was 91.0% . Most common grade 3-4 adverse events were anemia (29.3%), neutropenia (17.8%), neuropathy (4.9%), stomatitis (3.7%) and thrombocytopenia (1.8%). Conclusions: the ATP regimen was effective in treatment of locally-advanced TNBC, especially in patients with founder 5382insC BRCA1 mutation for Slavic population and deserves further investigation.