bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methods for selection of neoadjuvant treatment with chemotherapy for patients with hormone receptor-positive and HER2-negative with early breast cancer.
Authors: Gasol Cudos Ariadna , Morales Murillo Serafin , Tuset Der-abrain Noemí , Arbones Cid Laura , Morera Morillo Ester , Vilardell Felip , Sanchez Guzman Douglas , Canosa Morales Carles , Olivé Jordi Melé 
Published: June 2023

e12591 Background: Neoadjuvant chemotherapy (NCT) in hormone receptor positive and HER2 negative early breast cancer used to achieve a poor pathological response although patients with residual tumor inferior to 10 mm had a better significant survival. Methods: We analyzed the pathologic response (complete or major response if the residual tumor is inferior to 10 mm) in a consecutive series of 333 patients treated in our center considering clinicopathological classical variables, oncotype RS score, and non-response to previous sort course of hormonotherapy measured by the decrease in the Ki67 index. Results: Median age was of 51 years (24-87), median tumor size of 32mm (9-10) and 54% had nodal involvement. Pathologic complete response (pCR) was achieved in 16,5% and pathologic response according Symmans method type 0 and I in 33,6 %. Variables associated with pCR were initial tumor size < 30 mm (OR: 0,409; p: 0,004), progesterone receptor < 100 by histoscore (OR: 0,289; p: 0,00001) and Ki67 index > 30 (OR: 2,23; p: 0,008). When these 3 variables have been associated, the pCR increases by 45%. When use the ONCOTYPE RS score to select patients to NCT the pCR found was 23,5% that increases to 42% if the RS score was superior to 32 in a series of 136 patients. Considering the RCB pathologic response, RS>32 achieved a total of 73% of RCB 0-1 response. Finally, using the hormone non-response in patients with short course of hormonotherapy with non-decreases the Ki67 index, we found a 30% of pCR and 63% of RCB type 0-1 pathologic response. Conclusions: Selecting patients with early breast cancer with positive hormone receptors for neoadjuvant treatment with chemotherapy achieves a high response rate, going from 16% and reaching 40% in selected cases. The genomic platform and hormonal testing through Ki67 changes are very useful tools to select these patients. [Table: see text]
Role of plasma circulating HER2/EFTUD2 ratio in predicting pathological complete response (pCR) after neoadjuvant dual anti-HER2 therapy in HER2-positive breast cancer (HER2+ BC).
Authors: Chan Jeffrey CH , Cho William CS , Chow James CH , Bao Kelvin K H , Leung Alex KC , Szeto Michelle OY , Ho Connie HM , Yiu Harry HY 
Published: June 2023

e12592 Background: Achieving pCR following neoadjuvant chemo and anti-HER2 therapy is associated with a significantly better survival in HER2+ BC. There is currently a lack of a robust biomarker to predict pCR in HER2+ BC. Using EFTUD2 as chromosome 17 reference probe, circulating HER2/EFTUD2 plasma DNA copy number ratio (H-ratio) detected by droplet digital PCR (ddPCR) was shown to have high concordance with the tumor HER2 status. We aim to evaluate whether the change in H-ratio is associated with response to neoadjuvant dual anti-HER2 therapy. Methods: We prospectively recruited patients with HER2+ BC who received neoadjuvant taxane, trastuzumab and pertuzumab followed by radical surgery from May 2019 to April 2022. Serial plasma samples (n = 49) were collected at pre-treatment (Tpre), at 4th cycle (Tmid) and at completion of neoadjuvant treatment (Tpost). H-ratio was determined in each plasma sample using droplet ddPCR (QX200 ddPCR system, Bio-rad). H-ratio responders were defined as patients having a declining Tpost H-ratio, whereas patients having a rising or persistent Tpost H-ratio were defined as H-ratio non-responders. The relationship between pCR, H-ratio and various clinicopathological characteristics were evaluated by Spearman’s correlation, Fisher’s exact test and Wilcoxon signed-rank test. Results: Eighteen clinical stage II or III HER2+ BC patients with a median age of 56 years old (range 33 - 71) were included. The median H-ratio at Tpre, Tmid and Tpost were 1.27, 1.12 and 1.10, respectively. Higher Tpre H-ratio was significantly associated with larger tumor size (p = 0.004) and higher tumor grade (G1-2 vs G3; median H-ratio 1.15 vs 1.78; p = 0.024). Six patients (33.3%) were H-ratio responders. Ten (55.6%) of 18 patients achieved pCR after completion of neoadjuvant treatment. The pCR rate in H-ratio responders was significantly higher than the H-ratio non-responders (100% vs. 36.4%; p = 0.017). In predicting pCR, H-ratio response outperformed hormonal receptor (HR) negativity (HR- vs HR+; 72.7% vs 28.6%; p = 0.088) or high tumor grade (G1-2 vs G3; 66.7% vs 33.3%; p = 0.201). There was no association between pCR and Tpre/Tmid/Tpost H-ratio. With a median follow up of 22.8 months (range 8.2 - 41.8), there were no relapse or death. Conclusions: A high pre-treatment plasma circulating HER2/EFTUD2 ratio is associated with large tumor size and high tumor grade in HER2+ BC. The decline of HER2/EFTUD2 ratio after neoadjuvant dual anti-HER2 therapy predicts pCR, and may serve as a potential biomarker for treatment de-escalation.
Homologous recombination deficiency (HRD) status to predict the efficacy and prognosis of platinum-based neoadjuvant chemotherapy in patients with triple-negative breast cancer.
Authors: Jin Xuan , Chen Minyan , Chen Hanxi , Chen Lili , Lin Yuxiang , Wu Long , Tang Ganghuai , Li Weiwei , Huang Zhan , Li Qian , Zhu Changbin , Guo Wenhui , Fu Fangmeng , Wang Chuan 
Published: June 2023

e12605 Background: Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, and the predictive role of homologous recombination deficiency (HRD) in TNBC treated with platinum-based neoadjuvant chemotherapy (NCT) is not well described. Here, we sought to assess the association of HRD with pathological complete response (pCR) and survival outcomes in TNBC patients treated with NCT. Methods: 123 patients with stage II to III TNBC received one type of NCT regimen, including paclitaxel followed by anthracycline and cyclophosphamide-based NCT, and platinum-based NCT were enrolled in this study. The optimal cutoff of HRD score was determined by the Youden’s index on the ROC curve. HRD status was defined by either HRD score ≥ threshold or BRCA1/2 [tumor BRCA (t BRCA) and/or germline BRCA (g BRCA)] mutation. Logistic regression analysis was used to analyze the relationship between HRD and pCR. The Kaplan-Meier method, log-rank test and Cox regression were used for survival analysis. Results: A total of 104 FFPE and paired blood samples were successfully profiled from the 123 patients. The optimal cutoff for the HRD score of 58 was calculated based on the maximum Youden index value (0.235). HRD-High (HRD-H) was defined by either HRD score ≥ 58 or BRCA1/2 mutation. Of the 104 patients, 11.54 % (12) demonstrated BRCA mutation (g BRCA1 = 4, g BRCA2 = 4, t BRCA1=2 and t BRCA2 = 2), and another 46.15% (48) demonstrated HRD-H. In univariate logistic regression analysis, HRD status was significantly associated with a better pCR (p = 0.025, OR = 3.071, 95% CI: 1.154-8.175). Patients with HRD-H (p = 0.0103) or BRCA1/2 mutation (p = 0.0199) were all associated with superior event-free survival (EFS). There was a trend toward improved distant disease-free survival (DDFS), breast cancer–specific survival (BCSS), and overall survival (OS) in patients with HRD-H or BRCA1/2 mutation compared with HRD-Low or BRCA1/2 wild-type, although the differences did not reach statistical significance. Homologous recombination repair (HRR)-related genes mutation status was only associated with EFS (p = 0.0458). In multivariate logistic regression, Stromal tumor-infiltrating lymphocytes (sTILs) (p = 0.033, OR = 3.134, 95% CI:1.096-8.963) and HRD status (p = 0.015, OR = 4.014, 95% CI: 1.306-12.332) were both significantly associated with pCR. Conclusions: TNBC patients with HRD-H or BRCA1/2 mutation were more likely to benefit from platinum-based standard NCT.
INSIGHT-HER2BC: Real-world evidence of TCHP regimen to describe the best patient profile and open up questions—The interim results.
Authors: Zhukova Lyudmila , Sorokina Irina , Danilova Anastasia , Yurchenkov Alexander , Pokataev Ilya , Alekseenko Irina , Stroyakovsky Daniil 
Published: June 2023

e12607 Background: Neoadjuvant therapy (NAT) of TCHP regimen is approved for standard therapy for early and locally advanced HER2-positive breast cancer (eHER2+ BC) based on encourage TRYPHAENA and KRISTINE trials results. There are limited data regarding patients (pts) treatment outcomes after NAT TCHP in the routine clinical practice. Here we presented the 1st results of ambispective observational program to assess the efficacy and safety of cancer therapy in patients with solid tumors. Early HER2+ breast cancer group: INSIGHT-HER2BC. Methods: We ambispectively reviewed medical records of pts with eHER2+ BC who underwent NAT 6xTCHP (6 docetaxel/carboplatin + trastuzumab/pertuzumab) at three Moscow oncology centers since Jan’2017. This ongoing trial has launched in Feb’22. Here is presented descriptive analyses of pCR (ypT0/is, ypN0) rate for pts who completed NAT and 1-3 yrs. disease-free survival (DFS). Results: At the data cut-off (Jan’2023) 934 pts with HER2+ eBC underwent ≥ 1 cycle of NAТ. The median age is 54.3 y.o. (range: 22-78) where 36% pts were older 60 y.o.; 14% pts - younger than 40 y.o. 75% (571) pts had surgery results. pCR rate is related to KRISTINE trial: 58% (330) pts in the ITT (intention-to-treat) population vs 56% pts, respectively. pCR rate for pts with locally advanced BC is 55% vs 59% for operable BC (114/208 and 215/363 pts, respectively). There is difference in pCR rate achievement according to hormone status (HR+ vs HR-) and HER2 status (3+ vs 2+/ISH +). 1-yr. DFS for pCR group is 97% vs 94% for non-pCR; 2-yr. DFS is 83% vs 83%, respectively, and 3-yr. DFS 64% for pCR group vs 58% for non-pCR. In HR-HER2+ BC the biggest drop between pCR and non-pCR is registered at the 3-yr. DFS: 56% vs 22% while in HR+HER2+ there is almost equal decrease was observed every yr.: 97% vs 93% - 1st yr.; 90% vs 85% - 2nd yr.; 72% vs 68% - 3d yr. Conclusions: NAT TCHP is the effective regimen for HER2+ eBC in the real-world population. The efficiency is observed regardless of disease stage and age. However, there is clear unmet need to find new therapeutic options for HER2 (2+/ISH+) BC. Preliminary results of DFS is markedly lower than in TRYPHAENA and KRISTINE trials but in conjunction with another real-world evidence data. DFS in HR+HER2+ and HR-HER2+ pts likely reflects distinct tumor biology. The mature data for long-term outcomes are awaited. [Table: see text]
Retrospective analysis of Ki-67 as a predictive and prognostic marker for pathological complete response to neoadjuvant chemotherapy in breast cancer.
Authors: Randhawa Amritjot Singh , Roy Partha Sarathi , Hazarika Munlima , Ahmed Shiraj 
Published: June 2023

e12610 Background: According to GLOBOCAN 2020, breast cancer with an estimated 2.3 million new cases (11.7%) is the world's most common cancer. Ki-67 has been established as a proliferation marker in breast cancer. However, there are still some conflicting results on the clinical significance of Ki-67 as predictive and prognostic marker for effectiveness of neoadjuvant chemotherapy. In this retrospective study, Ki-67 is evaluated as predictive and prognostic marker for effectiveness of neoadjuvant chemotherapy (NACT). Methods: Study design: A retrospective observational single institutional study. Place of study: Tata memorial Centre - BBCI, Guwahati. Study period and duration: November 2018 to October 2021 (3 years). Study population: All female patients with biopsy-proven breast cancer. Inclusion criteria: All female patients with the diagnosis of breast cancer, who received NACT. Exclusion criteria: Patients who did not receive NACT, patients who did not undergo surgery after NACT, patients who lost to follow-up after chemotherapy, and patients whose pre-chemo Ki- 67 was not available. Sample size: 2272 patients were reviewed, out of which 127 patients were included in this study. Assuming 30% of patients have a complete response, allowing an error of 8% on these, 127 samples were required for the study at a 95% confidence interval. ROC (receiver operating characteristic) curve analysis was done to know the optimal cut-off value for the Ki-67 labeling index (LI) to discriminate response to treatment. Chi-square test was applied to know the relation between receptor status (ER, PR, HER2neu) and pCR. The pathological response was assessed in reference to Miller-Payne score. Results: Age <40years (22.83%), >40years (77.17%); commonest histology, IDC (95.28%); grade 2 (59.84%), grade 3 (40.16%); ER negative with pCR, 88.2%, p < 0.05; PR negative with pCR, 88.2%, p < 0.05; HER2 positive (treated with trastuzumab) with pCR, 55.8%, p < 0.05; triple negative with pCR, 41.2%, p < 0.05; chemo regimen, 4AC->4T (37%), 4AC->4TH (32.3%); pCR, 26.77% (n=34/127); and Ki-67 LI of 27%, sensitivity 95.4%, specificity 21%. Conclusions: Neoadjuvant chemotherapy is more efficient in tumors presenting with at least 32% Ki-67 expression. A high sensitivity of 95.4% and low specificity of 21% indicate Ki-67 LI is not a reliable predictive and prognostic marker. Other markers like ER, PR, and HER-2 influenced the disease outcome significantly. In our study, ‘PR negative’, ‘ER negative’, ‘HER-2 positive treated with trastuzumab’ and ‘triple negative’ were significantly associated with pCR (p < 0.05). This indicates that pCR rate depends on ER/PR/Triple negativity rates or the rate of HER-2 positivity treated with trastuzumab. Ki67 by itself is poor marker. However, when combined with ER/PR/HER2, it can become predictive of responses at cut off 27% in our study to differentiate the subgroups.
Neoadjuvant PARP inhibitors in patients with early HER2-negative breast cancer harboring BRCA 1/2 germline mutations: A systematic review and meta-analysis.
Authors: Dacoregio Maria Inez , Vilbert Maysa , Stecca Carlos , Michelon Isabella , Castro Caio , Amir Eitan 
Published: June 2023

e12611 Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of germline BRCA mutated (gBRCAm) breast cancer (BC) patients in the adjuvant and metastatic settings. Several studies have explored the role of PARPi in the neoadjuvant setting both with and without chemotherapy. Here, we explore the efficacy and safety of neoadjuvant PARPi in early HER2-negative BC patients. Methods: We searched PubMed, Scopus, and the Cochrane Library databases for randomized (RCT) and non-randomized clinical trials (non-RCT) that reported the proportion of patients with pathological complete response (pCR) after neoadjuvant PARPi and safety. Statistical analysis was performed using R software. Data were pooled using the random effects model. Results: Analysis included 3 RCTs and 4 non-RCTs, with 942 HER-2 negative breast cancer patients, 293 harboring a gBRCA 1/2 mutation. In a pooled analysis, gBRCAm carriers achieved a significantly higher rate of pCR than BRCA wild-type patients (56% versus 37%, p=0.04) with neoadjuvant PARPi. There was no difference in pCR when PARPi were combined with carboplatin (+/- chemotherapy) (40% versus 44%, p=0.69). Among RCTs (n=457) patients received PARPi in combination with either Paclitaxel plus Carboplatin (PCb) (85%) or with Paclitaxel alone (P) (15%). PARPi were associated with a higher pCR which approached, but did not meet statistical significance (51% vs 41%; Odds Ratio [OR]: 1.30, 95%CI 0.97 to 1.74, p=0.08). gBRCAm was associated with higher pCR compared to wild type in RCTs analysis (60% versus 48%; OR: 1.64, 95%CI 1.01 to 2.68, p=0.05). The most common adverse events (AEs) were cytopenias, nausea, fatigue, alopecia, and dizziness. Hematological toxicities were the most frequent serious AEs, including anemia (15%), neutropenia (22%), and thrombocytopenia (3%). The combination of PARPi and carboplatin was associated with higher hematological AEs (78% versus 46%; P=0.002). Conclusions: The addition of PARPi in the neoadjuvant setting improves pCR in early-stage HER2-negative breast cancer and germline BRCA 1/2 mutations, but not for unselected patients. Combination of PARPi with carboplatin does not improve pCR and leads to substantially worse toxicity. Further studies are warranted to identify the best neoadjuvant PARPi schema.[Table: see text]
DCE-MRI-derived microvasculature mapping and outcome prediction in patients with breast cancer.
Authors: Stefka Andrew T. , Feiger Bradley , Pfeiffer John R. , Pandey Tushar , Peterson Joseph R. , Antony Anuja K. 
Published: June 2023

e12614 Background: Tumor response to neoadjuvant therapy (NAT) in patients with breast cancer is related to perfusion in the tumor microenvironment and surrounding tissue. Direct and indirect measures of microvascular (MV) permeability could improve the ability to predict short- and long-term patient outcomes. Detection and quantification of circulating tumor DNA (ctDNA) is one such measurement that depends on microvasculature and has been shown to strongly correlate with both response to therapy and overall prognosis in a wide range of cancers. We hypothesized that a combination of ctDNA and numerical computations of MV permeability using pretreatment dynamic contrast-enhanced (DCE) MRI images (MV maps) can predict patient response to NAT and long-term survival outcomes. Here, we show how MV maps — computed from standard-of-care (SOC) imaging — improve upon ctDNA measurements in predicting pathologic complete response (pCR) following NAT as well as distant recurrence free survival (DRFS). Methods: DCE-MRIs were obtained for a sub-sample of I-SPY2 patients (n = 81) whose ctDNA levels were previously reported (Magbanua et al 2021). Tumors were segmented from pretreatment images by a convolutional neural network with manual verification. MV maps were computed using a Tofts-like model to describe the transfer kinetics between microvasculature and extracellular extravascular space. Microvasculature parameters (MVPs), such as median and skewness, were extracted from MV maps to describe the distribution of kinetic parameters in the intra- and peritumoral regions. Logistic regression was used to predict pCR with leave-one-out cross validation. Univariate Cox models were used to stratify DRFS. Results: MVPs exhibited a moderate correlation with pretreatment ctDNA levels (Spearman rho = -0.26; p = 0.018) and with pCR status in this cohort (rho = 0.25; p = 0.026). In a series of logistic regression models, a combination of SOC clinical features and ctDNA levels correctly classified 23% of true pCRs, with an F1 score of 0.58. This predictive power increased when informed by MV maps; 45% of true pCRs were identified after the addition of MVPs, and the F1 score increased to 0.68. In univariate Cox models, 24 MVPs significantly stratified DRFS (p < 0.05) when uncorrected for multiple hypothesis testing bias. The top MVP carried a hazard ratio 3.8 (95%CI 1.6 - 9.0) compared to 11.9 (95%CI 2.7 - 53.6) for ctDNA levels. Conclusions: DCE-MRI-derived kinetic features are calculated from SOC images with no additional clinical intervention. We found that MVPs substantially improve pCR prediction when added to models trained on ctDNA levels and clinical features. ctDNA levels and MVPs were predictive of DRFS to differing degrees of confidence. Although further validation in larger datasets is needed, this exploratory analysis uncovered a promising role for MV maps in predicting response to NAT as well as patient outcomes.
Tumor-infiltrating lymphocytes (TILs) for prediction of response to platinum-based neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC).
Authors: Abdullaeva Sheyda , Semiglazova Tatiana , Artemyeva Anna , Semiglazov Vladislav , Krivorotko Petr , Semiglazov Vladimir ,   N.N. Petrov National Research Oncology Institute, Saint-Petersburg, Russian Federation
Published: June 2023

e12620 Background: According to several previous trials the rate of pathological complete response (pCR) for patients with TNBC is increased when carboplatin is added to NACT. However, it is largely unknown which group of patients would truly benefit from platinum-based NACT and for whom chemotherapy could be de-escalated. Several clinical trials have evaluated the stromal TILs as an important prognostic and predictive biomarker in breast cancer. We assessed the pCR rates and the outcomes in patients with TNBC randomized to receive NACT ± Carboplatin regarding TILs status. Methods: The clinical data were obtained from 132 patients diagnosed with TNBC (ER&PgR < 10%) and treated with either anthracycline-taxane NACT (n = 68) or сarboplatin-based chemotherapy (n = 64) from 2017 to 2022 at N.N. Petrov National Medicine Research Center of Oncology. TILs were evaluated in 132 formalin-fixed paraffin-embedded tumor tissue samples stained with H&E at baseline biopsies according to guidelines from the International TILs Working Group. Classification of TILs into low ( < 10%), intermediate (≤10% to < 40%) and high (≥ 40%) levels was performed. Data are presented using the methods of descriptive statistics. The differences between groups were assessed using the Сhi-square test. P-values below 0.05 were considered statistically significant. Results: The proportion of patients who achieved a pCR was higher in the carboplatin group 66% than in patients without carboplatin 35% (OR 3,5; 95% CI 1,71-7,17; p = 0,0006). There were 25 (18.9%), 77 (58.3%) and 30 (22.7%) patients with low ( < 10%), intermediate (≤10% to < 40%) and high (≥ 40%) levels of TILs, respectively. In total, the tumors with high TILs had a pCR rate of 63.3%, compared with 46.1% for low TILs (OR 2,0; 95% CI 0,87-4,67; p = 0,097). No significant statistical difference in pCR rates was shown between carboplatin-based and standard NACT groups with high TILs - 71% and 54%, respectively (OR 2,06; 95% CI 0,45-9,30; p = 0,346). When analyzing a group with low TILs infiltration, the pCR was more frequent in the platinum-based 64% compared to 31% in the standard NACT group (OR 3,9; 95% CI 1,72-9,00; p = 0,0011). Conclusions: These data may support the de-escalation of carboplatin-based NACT in patients diagnosed with TNBC with high TILs infiltration. Further investigations are warranted to explore the predictive value of TILs in platinum-based NACT. [Table: see text]