bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world outcomes of long-term efficacy of T-DM1 after discontinuation due to limiting toxicity in patients with HER2-positive metastatic breast cancer.
Authors: Audi Blotta Daniella , Gomes Jessica Ribeiro , Moreira Shermann Brandão Rodrigues , Colosimo Danielle Fortes , Araujo Julio , Cavalcanti Gonçalves Ferreira Carolina , Forgiarini Elaine Aparecida , Buzaid Antonio C. 
Published: June 2023

e13034 Background: Antibody-drug conjugates (ADC) are widely used in the treatment of breast cancer (BC). In our service, we observed that a significant number of patients (pts) with HER2-positive metastatic breast cancer (MBC) treated with T-DM1 had long-lasting response and survival rates, even after discontinuing T-DM1 due to limiting toxicity. However, data are scarce regarding its long-term benefit. We performed a retrospective study to evaluate the long-term efficacy of T-DM1 in the treatment of HER2-positive MBC. Methods: Medical records of pts with HER2-positive MBC treated with T-DM1 between September 2013 and January 2023 were reviewed. We analyzed data in the overall population and in the subgroup of pts who discontinued T-DM1 due to only limiting toxicity and did not have disease progression or death for at least 12 months, without receiving other subsequent lines of treatment. The primary endpoints were progression-free survival (PFS) and overall survival (OS) from the start of the treatment with T-DM1 to disease progression or death for the overall population, and from the time of T-DM1 discontinuation to disease progression or death for the aforementioned subgroup. Secondary endpoints were objective response rate (ORR) and toxicity. Results: A total of 73 pts were included. In the overall population, ORR was 82.6%, median PFS was 12.7 months (CI95% 8-16) and median OS was 53.9 months (CI95% 34-73). 10 (13.6%) pts had T-DM1 discontinued due to only limiting toxicity and had no disease progression or death for at least 12 months. In this specific subgroup, 2 pts received T-DM1 as first line, 6 pts as second line, and 2 as third or more lines. At the start of T-DM1, 5 pts had visceral metastasis (3 liver, 2 lung), and 2 had only leptomeningeal involvement. Median age was 57 years (IQR 49-70) and median T-DM1 duration was 30 months (IQR 12-45). At the time of T-DM1 discontinuation, 9 pts presented complete response (CR) and 1 presented partial response (PR). 5 pts maintained CR, with no evidence of disease progression or death throughout the analyzed period. The PFS of these 5 pts, from the time of T-DM1 discontinuation to the last evaluation, was 35.6, 37.9, 40.5, 42.7 and 68.5 months. In the entire subgroup, median PFS was 22.5 months, 5-year OS was 66.7% and median OS was not reached. The adverse events that led to the T-DM1 discontinuation were thrombocytopenia (10%), nausea, vomiting and fatigue (10%), pneumonitis (20%), hepatic pseudocirrhosis (20%) and peripheral neuropathy (40%). Conclusions: Our experience suggests that pts with HER2-positive MBC who had T-DM1 discontinued due to limiting toxicity may derive long-term benefit. Further prospective studies are warranted to evaluate our findings, also including other ADC.
Shifting trends in the usage of trastuzumab with its biosimilar inception in India.
Authors: Ramanjinappa Nagendra , Upveja Kunvar Harsh , Agarwal Jatin 
Published: June 2023

e13037 Background: Biosimilars have the potential for cost savings and thus help increase access to treatment. The first trastuzumab biosimilar was introduced in 2014 in India. A qualitative study was conducted focusing on understanding the physicians’ perceptions on using trastuzumab biosimilars in HER2+ breast cancer (BC) and changes in trends from pre-biosimilar to post-biosimilar era in India. These study results were presented at ESMO Asia 2022 conference (https://www.annalsofoncology.org/article/S0923-7534(22)04219-3/fulltext). The current abstract utilizes sales data on trastuzumab to reexamine trends in biosimilar usage in this indication in India. Methods: Trends in patients treated with trastuzumab innovator or biosimilar were identified using data from Ipsos’ India Oncology Sales Audit (Jan 2014-Dec 2020), which reports Net Realized Value of all brands marketed by ~60 oncology companies across India. Data were collected using open-source intelligence and telephone interviews with sales/marketing personnel from pharmaceutical companies and distributors. The number of patients treated with trastuzumab was calculated using Microsoft Excel based on their body weight (assumed to be 60 kg), completing 6 months (9 cycles) of therapy and consuming 1 vial of 440 mg/cycle (8 mg/kg loading dose and 6mg/kg maintenance dose Q3W). Results: Approximately 68,000 HER2+ BC patients received trastuzumab from 2014-2020, out of which 46,000 received biosimilars and 22,000 innovators. Eighteen percent of patients were treated with biosimilars in 2014 which increased to 88% by end of 2020. There was a 17% decline in patients treated with innovator from the year 2017-2018, whereas patients treated with biosimilars grew by 229% in the same period, due to the launch of multiple biosimilars in this era. In the year 2020, there was a 15% decline (13% for biosimilar vs 30% for innovator) in the overall number of patients receiving trastuzumab which was primarily due to the impact of COVID-19. Similarly, pertuzumab usage increased 17 times from its introduction in 2015 till 2020. There has been decline in innovator trastuzumab patients and increase in the number of patients treated with biosimilar trastuzumab and pertuzumab in the last seven years; supporting our physician perception survey, wherein oncologists used pertuzumab with biosimilars in almost 45% of their patients. Conclusions: Findings from this data coincide with the physician perception survey suggesting increasing trend in usage of biosimilars in the last seven years. Biosimilars are preferred option amongst oncologists in India because of affordability and accessibility. The availability of quality biosimilars has the potential to reduce health care expenditure, and an effective supply also increase patient’s adherence to treatment.
Prognostic significance of estrogen receptor status in de novo metastatic breast cancer.
Authors: Chongxi Ren , Jianna Sun , Lingjun Kong , Ruizhen Luo , Kun Mu , Xiuzhen Jiang 
Published: June 2023

e13049 Background: The clinical behaviors of de novo metastatic breast cancer (dnMBC) differ according to hormone receptor (HR) status, but an association between estrogen receptor (ER) expression and clinical outcomes has not been established. Our study aimed to investigate the influence of different ER status on survival outcomes for patients with dnMBC. This study was the Medical Science Research Project of Hebei Province and approved by the Ethics Committee of the Ethics Committee of Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University (NO. 2017-AF29-058). Methods: Using hospital-based database, we identified patients with dnMBC diagnosed between 2010 and 2017, retrospectively collecting demographic data, tumor characteristics, treatment types and survival data. According to ER status, the patients were divided into ER-negative and ER-positive groups, and the propensity score matching (PSM) was used to balance the mixed bias. Overall survival (OS) was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results: A total of 322 patients were included. The median age was 53 (21-82) years, and the median follow-up was 8.5 years. The median OS for the PSM cohort was 29 months (95% confidence interval [CI], 26-35 months), and 5-year OS was 18.9%. OS differed significantly between the two groups (p = 0.0012), with a median OS of 36 months (95% CI, 32-41 months) in ER-positive group and 24 months (95% CI, 19-27 months) in ER-negative group. Multivariate analysis showed that clinical T-stage and initial metastatic sites were independent prognostic factors for survival in patients focused on ER status, with Ki-67 index, endocrine therapy and radiotherapy added to the ER-positive group, while initial and advanced chemotherapy added to the ER-negative group. Conclusions: For patients with dnMBC, there were substantial differences in OS according to ER status. ER-negative subtype is clinically different from ER-positive subtype, showing unfavorable tumor characteristics and poorer OS. We identified several prognostic factors that could guide therapy selection in this patient population. Clinical trial information: 20210957 .
Efficacy of abemaciclib versus tucidinostat after progression on palbociclib in patients with HR+/HER2− MBC: A multicenter retrospective cohort study.
Authors: Yuan Yang , Zhang Shaohua , Wang Tao , Wang Biyun , Wang Shusen , Shi Jing , Sun Tao , Yin Yongmei , Ouyang Quchang , Li Jianbin , Wen Yi , Zhang Lijun , Jiang Zefei 
Published: June 2023

e13056 Background: For patients with hormone receptor-positive HER2-negeative metastatic breast cancer (HR+HER2-MBC), switching to another cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) or target drug with different mechanism are reasonable treatment strategies post-CDK4/6i. However, no clinical data has been reported on which of the two strategies is more effective. We performed a retrospective cohort study to evaluate the efficacy of abemaciclib-based therapy versus tucidinostat-based therapy after progression on palbociclib. Methods: We identified patients with HR+/HER2- MBC who received abemaciclib-based therapy or tucidinostat-based therapy after progression on palbociclib from seven research centers in China. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate (CBR), PFS in patients with PIK3CA-mutant and PIK3CA wild-type, and safety. Results: Between Apr 1st 2020 and September 30th 2022, a total of 149 patients were included, of whom 73 patients received abemaciclib plus endocrine therapy(ET), and 76 patients received tucidinostat plus ET. The majority of patients had visceral disease (124/149, 83.2%) and ≥3 metastatic sites (76/149, 51.0%) at baseline, one third of patients (48/149, 32.2%) had previously been treated ≥3 lines of endocrine therapy in MBC setting. More patients received sequential therapy after palbociclib in abemaciclib group(49.3%) than that in tucidinostat group(30.3%). There were no statistically significant differences in other baseline characteristics between the two groups. Clinical benefit rate (CBR) was 38.4% (28/73) in abemaciclib group and 17.1% (13/76) in ET plus tucidinostat group (p=0.0037). There was significant difference in PFS between abemaciclib group and tucidinostat group in both the whole population (5.0 months vs. 2.0 months; HR 0.44; 95%CI 0.31-0.64; P＜0.001) and propensity score matched population. PIK3CA mutations occurred in 44.20% of patients who had undergone multigene sequencing. PIK3CA-mutant showed a negative effect on PFS of abemaciclib-based therapy. The most common any grade and grade 3-4 adverse events was neutropenia in either group. Common non-hematological toxicity occurred in abemaciclib group was diarrhea, and were increased AST, nausea, vomiting in tucidinostat group. Conclusions: Abemaciclib-based therapy improved clinical benefit rate and prolonged PFS compared with tucidinostat-based therapy, providing a superior treatment option in patients progressed on palbociclib.
Comprehensive molecular profiling from liquid and tissue for analysing the somatic mutational landscape in an Indian breast cancer cohort.
Authors: Rohatgi Nitesh , Limaye Sewanti Atul , Bahl Ankur , Sirohi Bhawna , Sahni Sidharth , Patil Darshana , Datta Vineet , Limited Datar , Crook Tim , Kurzrock Razelle , Cristofanilli Massimo 
Published: June 2023

e13080 Background: Breast cancer is a genetically and clinically heterogeneous entity, with high prevalence in the Indian population. The primary objective of this study was to characterize the somatic mutational landscape of metastatic breast cancer in Indian patients from tumor and liquid specimens. Methods: We performed molecular profiling of 341 tumor tissue specimens and 901 blood specimens from individual breast cancer patients, with paired tissue and blood processing in a sub cohort (n=101). Targeted NGS evaluating single nucleotide alterations, copy number alterations, and fusions was performed on these specimens. Results: In the cohort with tissue-based sequencing (n = 341), TP53 was the prevalently altered gene (55%). PIK3CA and ESR1 mutations were detected in 32% and 9%, respectively. BRCA1/2 alterations were detected in 10.8%, ARID1A in 7%, KEAP1 in 6%, NF1 in 6%, and ATR in 6%. ERBB2 amplification was observed in 10% of the cases. ESR1 gene fusions were detected in 3.7%. This is clinically relevant as along with other ESR1 resistance mutations, ESR1 fusions are also known as recurrent drivers of endocrine therapy resistance and are impervious to ER-targeted therapies. In a sub cohort comprising 255 specimens, TMB analysis showed a median TMB of 5 mut/Mb (range 1 - 88 mut/Mb), and 15.3% specimens with TMB-High (≥10 mut/mb). The ctDNA analysis (n = 901) revealed TP53 being the most altered (41%) gene, followed by PIK3CA (23%), ESR1(11%), EGFR (6%) and GNAS (4%). Acquired resistance mutations in ERBB2 were identified in ctDNA analysis liquid biopsy from two patients treated with HER2-targeted therapy and were absent in corresponding tissue samples. Mutations in ESR1 were more commonly seen in liquid biopsy than paired tissue, indicating this acquired resistance alteration being better captured in ctDNA than tissue due to tumor heterogeneity and tumor evolution. This indicates causative role for ESR1 mutations in endocrine resistance but not in disease pathogenesis. Conclusions: We report the largest liquid biopsy study reporting the genomic landscape from breast cancer cases of Indian origin along with tissue based molecular landscape. High concordance of liquid for PIK3CA alteration and higher sensitivity for detection of resistance conferring alterations like ESR1 and ERBB2 shows utility of liquid biopsy profiling. It reinforces the utility of liquid biopsy as effective tool that reveal clinically relevant information including mutational status and therapeutic options and seem more relevant in acquired resistance settings. [Table: see text]
Exploring the effects of inhibiting miR-10b on breast cancer stemness and metastasis.
Authors: Al-Qadi Nasreen , Halim Alan , Mackie Hussein , Sempere Lorenzo , Moore Anna 
Published: June 2023

e13084 Background: There are currently limited effective therapeutic options for metastatic breast cancer, and none target the metastatic process. MiR-10b is a major driver of breast cancer cell invasion and migration. Our lab has demonstrated its importance in metastatic cell viability, positioning miR-10b as a target for metastatic breast cancer. Our previous studies demonstrated that delivery of a novel therapeutic consisting of antisense anti-miR-10b oligomers conjugated to magnetic nanoparticles (termed MN-anti-miR10b) prevented metastases in vivo. These studies led us to hypothesize that MN-anti-miR10b affects the viability of a stem cell-like population of cells within primary tumors that otherwise would have formed metastases. Here, we investigate the relationship between miR-10b and breast cancer cell stemness and the effects of miR-10b inhibition by MN-anti-miR10b on breast cancer cell stemness. Methods: MDA-MB-231 breast cancer cells were sorted based on surface markers into stem-like (CD44+/CD24-) and non-stem-like (CD44-/CD24-) populations, and their miR-10b expression levels were quantitated. Then, unsorted MDA-MB-231 cells were treated with MN-anti-miR10b to determine the effects of miR-10b inhibition on the expression of EPCAM, a marker for cancer cell stemness. Lastly, MCF-7 breast cancer cells were cultured in mammosphere medium (which selects for stem-like cells and induces spheroid formation) and treated with MN-anti-miR10b to establish the phenotypic effect of miR-10b inhibition on cancer cell stemness. Results: We found that stem-like MDA-MB-231 cells displayed >2-fold miR-10b expression compared to non-stem-like cells. Accordingly, alongside a 70% reduction in miR-10b expression, treatment of MDA-MB-231 cells with MN-anti-miR10b reduced EPCAM expression by 65%. Treatment of MCF-7 spheroids with MN-anti-miR10b resulted in significantly greater cell dissociation from the spheroid compared to controls. Conclusions: These results support the hypothesis that inhibition of miR-10b with MN-anti-miR10b inhibits breast cancer cell stemness. This provides an explanation for the therapeutic efficacy of MN-anti-miR10b observed in mouse breast cancer metastasis models. Future studies will further investigate this relationship and shed light on how miR-10b can be optimally targeted to treat metastatic breast cancer in humans.
Correlation analysis to assess surrogate endpoints for overall survival (OS) in triple-negative breast cancer (TNBC).
Authors: Pérez-Granado Judith , Kalucha Ankit , Gala Kinisha , Bodriagova Olga , Vidal Laura , Larvol Bruno , Gramling Mark , Saini Kamal S. 
Published: June 2023

e13089 Background: The use of surrogate endpoints can help reduce the trial duration and cost which is important for aggressive diseases such as TNBC. Previous studies suggest progression-free survival (PFS) may serve as a surrogate for OS in metastatic TNBC. We aim to evaluate PFS and additional surrogate endpoints for their correlation with OS in localized and advanced TNBC. Methods: TNBC phase 3 trials and pooled analysis as well as trials including TNBC subgroups, were identified through a systematic search using LARVOL CLIN, PubMed, clinicaltrials.gov, and conference proceedings. Out of these, trials reporting median survival and hazard ratios (HR) for both OS and surrogate endpoints were considered for further statistical analysis. Surrogate endpoints reported by fewer than 4 trials were excluded from the study. Pearson correlation (r) and determination coefficient (R2) were calculated to assess surrogacy between Median OS and Median PFS, HR OS and HR PFS, HR disease-free survival (DFS), and invasive disease-free survival (IDFS). Weighted regression analysis was conducted controlling for sample size among trial arms. Results: 26 TNBC cohorts and 2 pooled analyses evaluating PARP, PD-1, PD-L1 inhibitors, and chemotherapies were included. The association analysis results are shown. There was a significant correlation between median OS and median PFS (r = 0.73, p value = 1.026×10−6) as well as between HR OS and HR PFS (r = 0.61, p value = 0.009). There was also a significant correlation between HR DFS and HR IDFS with HR OS (r = 0.92, p value = 0.003; r = 0.99, p value = 0.014). Conclusions: PFS is significantly correlated with OS in TNBC across diverse therapies. Also, HR PFS, HR DFS, and HR IDFS are significantly correlated with HR OS. Overall, these results illustrate that PFS could be used as a surrogate for OS in TNBC. Subsequent studies should include early-phase trials to increase association robustness and enable correlation comparison between the diverse mechanism of actions and other surrogate endpoints. [Table: see text]
A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer.
Authors: Zhao Weihong , Zhang Zheng , Zhang Yadi , Chen Yimeng , Zhu Yimin , Liu Chuanling , Shao Jiakang , Zhang Li , Liu Mei 
Published: June 2023

e13090 Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. The lack of specific targets leads in fewer effective treatments and poor prognosis. Immunotherapy has become a new generation of treatment approach in addition to surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapy. Immune checkpoint inhibitors (ICIs) have been widely used in the clinical treatment of various tumors and changed the landscape of tumor treatment, but the data from real-world studies of ICIs for TNBC remain limited. Methods: Clinical data of patients with advanced TNBC treated with ICIs in Chinese People’s Liberation Army General Hospital were collected from January 2004 to December 2022. The effect of different factors on patient response and prognosis was analyzed using Kaplan-Meier survival curves. The relationship between clinical, pathological characteristics, hematological indicators, and efficiency were analyzed using univariate and multifactorial Cox regressions. Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-free Survival (PFS), Overall survival (OS), and adverse events (AEs) were assessed. Results: Eighty-one patients were enrolled in the study. Median follow-up was 26.3 months (range, 16.0 - 36.6 months). Confirmed ORR was 32.1% and DCR was 64.2%. The median PFS was 4.2 months and the median OS was 11.0 months. Eastern Cooperative Oncology Group (ECOG) performance status score ≥ 1, applying ICIs in 2nd and later lines, with liver metastases, with more than two sites of metastases, lactate dehydrogenase (LDH) ≥ 194.3 U/L, alkaline phosphatase (ALP) ≥ 104.7 U/L, neutrophil-to-lymphocyte ratio at baseline (bNLR) ≥ 2.7, NLR before the second dose of immunotherapy (NLR2) ≥ 2.2, platelet to lymphocyte ratio before the second dose of immunotherapy (PLR2) ≥ 165.6 were associated with a poorer prognosis. Patients with effective initial treatment, tumor - infiltrating lymphocytes (TIL) ≥ 20%, derived neutrophil-to-lymphocyte ratio (dNLR) ≤ 1.9, LDH < 194.3 U/L and bNLR < 2.5 prior to ICI treatment have a better prognosis. Conclusions: ICIs were effective in advanced TNBC with tolerable adverse effects, and we have identified a series of biomarkers associated with PFS and OS. Randomized controlled clinical trials are warranted to validate our findings.