bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined role of the neutrophil/lymphocyte ratio and Neo-Bioscore in neoadjuvant therapy in HER2-positive early breast cancer.
Authors: Sánchez Escudero Laura , Cobelas Cartagena Stephanie S , Morales Pancorbo David , Bayo Juan L. 
Published: June 2023

e12613 Background: High neutrophil/lymphocyte ratio (NLR) is considered a poor prognostic factor in triple negative breast cancer but its role in HER2-positive early breast cancer (eHBC) and its relationship with Neo-Bioscore (Nb) scale (NbS) in neoadjuvant therapy (NeoT) has not been established. They could be predictive factors of response to double antiher2 blocking with Pertuzumab (Pz) and Trastuzumab (Tz). Methods: The efficacy of Chemo-trastuzumab (ChTz) versus Chemo-trastuzumab-pertuzumab (ChTzPz) was assessed in patients with eHBC treated at our center. We performed a comparative analysis of the pathological complete response (pCR) according to pre-treatment NLR and clinical NbS (Grade + clinical stage + estrogen receptor (ER) previous to NeoT) Univariate and multivariate retrospective study were performed using xi-square and binary logistic regression (v21 SPSS software). Results: 150 patients (Pts) with stage IIA to IIIC HBC were treated from 2014 to 2022. Mean age 52 years. 83 Pts (55.3%) received Chem-Tz and 67 Pts (44.7%) Chem-Tz-Pz. In the overall sample, the pCR was higher in the Tz-Pz group, 60% Vs 40%; OR 3.05 (95% CI 1.5-5.9). In the NLR >2 subgroup, pCR was higher in Pts treated with Pz-Tz, 66.7% vs 33.3%; OR 4.2 (95% CI 1.5 – 11.07) If we combine Pts with both NLR ≥2 and clinical Nb ≥2, the pCR was significantly higher in the Tz-Pz group, 68.4% vs 11.8%; OR 16.25 (95% CI 2.7-94.8). In the multivariate analysis, Nb≥2, NLR ≥2 and double blockade with Pz are related to an increase in pCR (OR 1.29, OR 1.076 and OR 2.90 respectively), with significance for Pz (p=0.001). Conclusions: In our review, the combined use of Pz-Tz proves to be a more effective treatment than simple Tz blockade in the treatment of poor prognosis breast cancer. High NLR, despite being a poor prognostic factor, seems to be a predictor factor of pCR in Pts treated with Pz-Tz. The increase in NLR and clinical NbS are factors to take into account to predict the efficacy of NeoT in eHBC Pts. [Table: see text]
Assessment of efficacy and safety of dose-dense doxorubicin and cyclophosphamide (ddAC) in combination with pembrolizumab in early-stage, triple-negative breast cancer.
Authors: White Olivia , Dent Susan Faye , Westbrook Kelly E. , Moore Heather 
Published: June 2023

e12618 Background: KEYNOTE-522 demonstrated significant improvement in pathologic complete response (pCR) and event free survival (EFS) for early stage triple negative breast cancer (TNBC) patients (pts) treated with pembrolizumab (PEMBRO) and chemotherapy (carboplatin/paclitaxel weekly followed by doxorubicin/cyclophosamide (AC) every 3 weeks) in the neo/adjuvant setting. Standard of care prior to KEYNOTE-522 was AC every 2 weeks (dd), however, implementation of ddAC becomes impractical when accommodating 21-day PEMBRO dosing and creates concern for compromised efficacy. KEYNOTE-555 demonstrated feasibility of every 6-week PEMBRO dosing. We modified the KEYNOTE-522 regimen to employ ddAC with PEMBRO every 6-weeks with the aim to maximize clinical outcomes while reducing time spent in the infusion center. The primary objective is to compare the rate of pCR using ddAC plus 6-week PEMBRO versus PEMBRO and AC every 3 weeks. Secondary objectives include: safety of concomitant chemoimmunotherapy by comparing the incidence of adverse events (AEs) with PEMBRO (every 3 or 6 weeks), assessing rates of held cycles or dose modifications, and assessing toxicity of concomitant capecitabine and PEMBRO in the adjuvant setting. Methods: This was a retrospective, single-center, cohort study at Duke University Hospital (DUH). Results reported via descriptive statistics. Adult pts with clinical stages I-III TNBC were included in this study. Pts must have completed four cycles of AC. Pre-specified data collection points were obtained from the electronic health record and entered into a secure database. Results: A total of 25 female pts treated at DUH were included. The rate of pCR was 64.3% (AC) versus 81.8% (ddAC). All patients experienced at least one adverse event with their immunochemotherapeutic regimen. The most common IO-induced toxicities included thyroid-associated AEs (37.5%) and rash (37.5%). There were no grade 3 or 4 IO-induced toxicities reported. Five patients were on concomitant adjuvant capecitabine and PEMBRO for residual disease. One patient in each arm required dose adjustments for capecitabine and 3 patients had at least one deferred cycle. One patient experienced AEs associated with capecitabine. No patients had toxicities attributable to adjuvant PEMBRO. Conclusions: In this small single center study, the administration of neoadjuvant ddAC with PEMBRO at 400mg every 6 weeks was deemed feasible with no excess toxicity. There was a trend towards improved efficacy for patients treated with ddAC with PEMBRO. Additionally, safety endpoints were similar between groups. This dosing strategy allows for optimization of therapy with the incorporation of ddAC and adjuvant capecitabine, thus potentially improving outcomes in TNBC patients. Larger cohort studies, in the real-world setting, are needed to confirm these findings.
Decreased HER2 expression in residual disease following neoadjuvant therapy in patients with HER2-positive breast cancer.
Authors: Paredes Mogica Jan , Tang Haiming , Fischbach Neal A. , Zhan Haiying 
Published: June 2023

e12621 Background: Human epidermal growth factor receptor-2 (HER2) overexpression is a defining feature of roughly 20% of localized breast cancer and represents a critical target for therapy. Since the demonstration that residual disease (RD) after neo adjuvant therapy (NAT) is associated with worse prognosis and that adjuvant ado trastuzumab emtansine (tDM1) improves survival, NAT has become the standard of care for localized HER2+ breast cancer. Retesting for HER2 overexpression post resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy. The objective of this study was to evaluate the association of pre and post neo adjuvant therapy HER2 immunohistochemistry (IHC) expression on breast cancer outcomes in our institutional database. Methods: After IRB approval, data was gathered for patients with localized HER2+ breast cancer receiving NAT including trastuzumab/pertuzumab at Yale Cancer Center between 2012 and 2022. Pathologic complete response (pCR) was defined as no residual invasive tumor in breast and lymph nodes. Patients were divided into 3 cohorts by response and HER2 IHC: Cohort 1 pCR Cohort 2 pre-treatment 3+/post treatment 1-2+, and Cohort 3 pre-treatment 3+/post treatment 3+. A Kaplan-Meier survival analysis was done to assess recurrence free survival at 36 months. Results: Within the specified time interval, we identified 104 patients with localized HER2-IHC 3+ breast cancer who received neoadjuvant therapy. The pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had RD. Among patients with RD, 58.9% (23/39) remained HER2 IHC 3+ and 41% (16/39) had decreased HER2 expression IHC1+/IHC 2+. Median follow-up was 27.9 months at time of analysis. In patients with HER2 3+ RD 26% (6/23) developed local recurrence or distant metastasis while none of patients with HER2 IHC 1+ or 2+ RD had relapse ( p= 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis showed a significant difference between the 3 groups (log rank p= 0.004). Conclusions: In our retrospective cohort, decreased HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to select patients for more or less aggressive adjuvant therapy, stratify patients in adjuvant trials, and identify patients who may benefit from more intensive post therapy surveillance.
De-escalating therapy dilemma in small HER2 positive node negative breast cancer.
Authors: Hajjaji Nawale 
Published: June 2023

e12626 Background: Neoadjuvant therapy (NAT) is the standard of care for locally advanced HER2 positive breast cancer (BC) and provides pathologic complete response (pCR), a key prognostic factor and indicator to decide whether to escalate to adjuvant T-DM1 in case of residual disease, as per the KRISTINE trial. However, optimal sequencing of treatment (NAT vs. surgery first) is less clear in T1cN0 (stage I) HER2 positive BC. Moreover, the long-term follow-up of the Adjuvant Paclitaxel and Trastuzumab (APT) trial showed that deescalating chemotherapy is a possible strategy for small HER2-positive node negative breast cancers when tumor size is 3 cm or less. In clinical practice, there is a recurrent debate in multidisciplinary boards to decide the adequate strategy in small HER2 positive node negative BC. Although these tumors are considered of good prognosis, recent results by An et al. 2022 fuels the debate. They showed in a large observational cohort that T1N0 HER2 positive BC APT eligible treated with NAT and not achieving pCR have similar survival to patients with T2N0 tumors with residual disease, suggesting a higher risk group among small tumors.The aim of the study was to analyze the profile and outcome of APT eligible patients treated with NAT using a detailed tumor size breakdown. Methods: APT eligible patients treated with NAT were identified among a real-world cohort of 340 early HER2 positive BC patients receiving NAT at Oscar Lambret Cancer Center (Lille, France). The outcome of the APT eligible patients (n = 115) was analyzed according to tumor size ( < 15mm, 15-20mm, 21-30mm). Results: All patients were female with a median age of 54 years and received neoadjuvant anthracyclines followed by taxanes and trastuzumab. The ratio of hormone receptor (HR) positive / HR negative tumors was 72% / 28%. A similar distribution of grade 2 / grade 3 tumors was observed. Up to 75% of the patients did not have a complete pathologic response to NAT. In HR positive, the pCR rate was 43% in HER2 positive tumor of less than 15mm, 26% in tumors of 15-20mm, 25% in tumors of 21-30mm, and 32% in tumors of 31-50mm. In HR negative tumors, pCR rate was 81% in tumors of 15-20mm, 56% in tumors of 21-30mm, and 67% in tumors of 31-50mm. Conclusions: These results showed that APT eligible small HER2 positive and HR positive tumors had low chemosensitivity leading to adjuvant treatment escalation as per standard of care. It raises questions about the appropriate selection of patients for de-escalation in this population subset.
Association of KMT2C loss-of-function mutations in circulating tumor DNA and prolonged response to the combination of PARPi and PI3Ki.
Authors: Batalini Felipe , Ke Shizong , Liu Ruolin , Blewett Tim , Rhoades Justin , Gulhan Doga , Konstantinopoulos Panagiotis A. , Matulonis Ursula A. , Adalsteinsson Viktor , Wulf Gerburg M. 
Published: June 2023

e13003 Background: The emergence of somatic KMT2C mutations has been associated with resistance to various treatments, including chemotherapy and endocrine therapy in patients with estrogen receptor-positive breast cancers. The impact of these mutations in patients treated with poly-ADP ribose polymerase inhibitors (PARPi) and phosphatidylinositol-3-kinase inhibitors (PI3Ki) is unknown. Methods: Circulating tumor DNA (ctDNA) was obtained from plasma and peripheral blood at different time points from 38 patients prior to treatment with the combination of the PARPi olaparib with the alpha-specific PI3Ki alpelisib (NCT01623349). CtDNA was also collected immediately before the first cycle and at the time of disease progression. CtDNA underwent deep targeted sequencing (tumor-normal pairs, 397 genes (2Mb) at 25,000x somatic and 10,000x germline) at the Broad Institute of MIT and Harvard. Variants that were exonic, non-synonymous, and predicted to lead to loss-of-function were considered mutations. Cohorts were stratified according to the presence or absence of the genomic alteration, and progression-free survival was compared with the Kaplan-Meier method and log-rank test. A Cox regression was performed using age, tumor type, germline BRCA1/2 mutation status, performance status, and number of previous lines of treatment as covariates. Results: The KMT2C gene was one of the 3 genes most frequently mutated in our cohort, affecting 5 patients (15%) after the exclusion of those with variants with non-deleterious alterations. The other 2 commonly mutated genes were TP53 (76%) and PIK3CA (15%). In the comparison of patients based on these most common mutations, we identified that patients with somatic KMT2C mutations (n=5) have longer mPFS than those that were wild type (n=28): mPFS 386 vs. 151 days, log-rank p = 0.025. Cox proportional hazards model accounting for age, tumor type, germline BRCA1/2 mutation status, performance status, and number of previous lines revealed a hazard ratio of 0.16; p = 0.007. All somatic KMT2C mutations were proximal to the SET domain critical for methyltransferase activity. Upon progression, the KMT2C-mutated clones were suppressed to below the detection level of mutation calling algorithms. Analysis of the raw files revealed that the clones were suppressed but not eliminated. Conclusions: While the emergence of KMT2C has been reported to be associated with cancer progression and resistance to different therapies, patients with deleterious KMT2C mutations in the ctDNA may benefit from therapy with PARPi and PI3Ki.
PI3KCA mutation prevalence and outcome among patients with metastatic breast cancer in Bulgaria treated with first-line endocrine therapy.
Authors: Gencheva Radostina , Hadjidekova Savina , Petrova Mila , Krustev Dimo , Kraleva Petya , Zhbantov Georgi , Conev Nikolay Vladimirov , Stoyanov Dragomir Svetozarov , Arabadjiev Jeliazko Iliev , Tazimova Eliz , Bachurska Svitlana , Galev Ivan , Eneva Mariyana , Tsvetkova Mariela , Staneva Rada , Dimitrova Eleonora , Hadjiev Rossen , Donev Ivan 
Published: June 2023

e13005 Background: There are phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations in 30-40% of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2) tumor samples. Nevertheless, clinical outcomes in this group vary amongst research trials. Methods: We sought to determine the incidence of PIK3CA mutations in Bulgarian patients with metastatic HR+, HER2-negative breast cancer, as well as to evaluate and compare progression-free survival (PFS) in the real world between wild-type (WT) and mutant cohorts. In this multicentric retrospective analysis, 250 tissue samples were collected between 2016 and 2022 from three Bulgarian oncology centers. Qualitative real-time PCR was used to determine the existence of PIK3CA mutations. The median follow-up time was 28 months. Results: The mean age was 57.6±11.6 years for the mutant cohort and 56.5±12.2 for the wild-type cohort (p=0.52). The percentage of patients with visceral metastatic disease was 58.8% (n=147). Postmenopausal patients were 84.3% (n=210). PIK3CA mutation prevalence was 29.2% (n=73). The most prevalent mutation was found in exon 20: H1047R (9.2%). Among all clinicopathological features, we observed only a significant relation between the presence of a mutation and a metastatic stage at diagnosis (p = 0.002). 67.1% of the patients received endocrine therapy (ET) + CDK4/6 inhibitor as first-line therapy, while the remainder receive ET monotherapy. Patients with PIK3CA mutation did not have significantly different median PFS compared to WT patients (32 months (95%, CI: 22-40) versus 24 months ((95%, CI: 21-36) (p=0.45)); HR=0.86 (95%, CI: 0.5-1.3) (p=0.46). In propensity matching score analysis (matched for treatment utilized as a first line ET, menopausal status, and locations of metastatic disease), we confirmed our finding (36 months (95%, CI: 20-40) versus 26 months (95%, CI: 21-38), p = 0.69). Conclusions: We demonstrated that the prevalence of PIK3CA mutations in Bulgarian patients is comparable to that reported in other countries. Our findings suggest that the presence of a PIK3CA mutation has no effect on the efficacy of endocrine therapy of first-line treatment. In summary, our study provides valuable insights into the topic, but limitations including the retrospective design and small sample size suggest that the findings need to be replicated by more robust studies and larger sample sizes to draw definitive conclusions.
Real-world safety and effectiveness of CT-P6 (biosimilar trastuzumab): A post-marketing surveillance study in Korea.
Authors: Park Min-Ho , Kim Tea Hyun , Seo Jae Hong , Park Jung Ho , Seong Min-Ki , Park Keon Uk , Kim Min Kyoon , Chang Myungchul , Koh Su-Jin , Lee Moon Hee , Lim Seung Taek , Yoo Young Bum , Oh So Yeon , Kim Sung Hyun , Park Tae Hong , Ju Hana , Baek Eric Hyungseok , Kim Sinhye , Kim Nahyun , Lee Eunkyung 
Published: June 2023

e13025 Background: CT-P6 is a biosimilar trastuzumab product approved in many countries worldwide, including the European Union and the United States. This study aims to confirm the safety and effectiveness of CT-P6 in routine clinical practice settings for the approved indications of HER2-positive metastatic breast cancer (MBC), early breast cancer (EBC), and metastatic gastric cancer (MGC) in the Republic of Korea. Methods: The observational, prospective, multi-center, post-marketing surveillance (PMS) study was conducted from October 5, 2018 to October 4, 2022, on Korean patients diagnosed with MBC, EBC or MGC and newly treated with CT-P6 regardless of previous treatment of trastuzumab products other than CT-P6. Patients receiving at least one CT-P6 treatment according to the prescribing information and being monitored for safety and effectiveness were included in these analyses. Safety was evaluated by all types of adverse events (AEs), including adverse drug reaction (ADR), and serious adverse event (SAE); for up to a year after the first dose of CT-P6. Safety was further summarized by background factors (demographic and clinical characteristics) for subgroup analysis to identify variables independently affecting the incidence proportion. As for effectiveness, disease-specific clinical response (by best overall response for MBC and MGC; disease progression, and pathologic complete response (pCR) for EBC) were assessed for up to one year. Results: The safety population included 642 patients (94 MBC, 494 EBC, 54 MGC). For patients with MBC, AEs occurred in 71.28%, ADRs in 48.94%, and SAEs in 19.15%. For EBC, AEs occurred in 43.52%, ADRs in 26.52%, and SAEs in 6.48%. In case of MGC, AEs occurred at a rate of 79.63%, ADRs at 40.74%, and SAEs at 14.81%. Overall, the incidence of ADR was statistically different for groups ≥65 of age ( p=0.0323); comorbidity or complication, especially with cardiac disorder ( p=0.0018); and previous chemotherapy ( p=0.0002). In terms of effectiveness, positive outcomes were observed. Conclusions: CT-P6 administered to Korean patients according to the prescribing information was well tolerated, with no new safety signals identified. The safety and efficacy profiles of CT-P6 in a real-world population were consistent with those observed in the previous clinical studies. [Table: see text]
Palbociclib, trastuzumab, pyrotinib and fulvestrant in patients with brain metastasis from ER/PR positive, HER-2 positive breast cancer: Report from an interim analysis of a multicenter, prospective study in China.
Authors: Hong Ruoxi , Xu Fei , Lu Yongkui , Du Caiwen , Yuan Zhongyu , Shi Yanxia , Xia Wen , Wang Shusen 
Published: June 2023

e13032 Background: HER2-positive breast cancer patients are at a high risk of developing metastases in brain. Effective treatment should involve anti-HER2 targeted therapy. This aim of this study is to evaluate the activity of the chemo-free combination of palbociclib, trastuzumab and pyrotinib with fulvestrant in ER positive, HER2-positive breast cancer patients with brain metastasis. Methods: We did a multi-center, prospective trial in three hospitals in China. Female patients older than 18 years who had whole brain radiotherapy-naive ER/PR positive, HER2-positive brain metastases with an Eastern Cooperative Oncology Group performance status of 0–2 were treated with palbociclib, fulvestrant, combined with trastuzumab and pyrotinib, and until disease progression or intolerable adverse effects. The primary endpoint was objective response rate in the central nervous system (CNS), as assessed by investigator per the modified Response Evaluation Criteria In Solid Tumours (version 1.1). The study is still ongoing and recruiting. Here we report the results of an interim analysis. The study is registered with ClinicalTrials.gov, NCT04334330. Results: Between December 4, 2020 and November 2, 2022, 15 patients were enrolled. Eleven patients had prior exposure to trastuzumab. In the 14 patients who were evaluable for clinical response, the objective response rate in the CNS was 28.6%? (95% CI, 8.4% - 58.1%). At a median follow-up of 6.3 months (range, 2.1-14.3 months), the median PFS was 10.6 months (95%CI, 4.3 – 16.9 months). The time to progression in the CNS was 8.5 months (95%CI, 5.9 – 11.1 months). Conclusions: Combination of palbociclib, trastuzumab and pyrotinib with fulvestrant represents an active chemo-free treatment strategy in hormonal receptor positive, HER2-positive breast cancer patients with brain metastasis. Clinical trial information: NCT04334330 .