bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic analysis of the tumor microenvironment in Asian and Native Hawaiian and Pacific Islander patients with triple negative breast cancer.
Authors: Nguyen Edward , Cheng Shirley , Chang Connie , Nguyen Ba Thong , Khadka Vedbar , Deng Youping , Killeen Jeffrey , Fukui Jami Aya 
Published: June 2024

e12644 Background: Triple negative breast cancer (TNBC) accounts for approximately 10- 20% of breast cancer cases and has the worst overall survival and prognosis compared to other subtypes. Unlike other subtypes, patients with TNBC are responsive to neoadjuvant therapy. A higher percent of stromal tumor infiltrating lymophocytes (sTILs) in the tumor microenvironment of TNBC correlates with an improved prognosis. Previous studies demonstrate that Native Hawaiians and Pacific Islanders (NHPIs) and Asians have equivocal percent of sTILs. Yet NHPIs have a higher mortality rate at 24.9% compared to Asians at 11%. Our study aims to molecularly characterize the tumor microenvironment in a diverse population of patients with TNBC who received neoadjuvant therapy. Methods: Retrospective chart review was conducted on 12 Asians and 12 NHPI patients with early stage TNBC from 2015 to 2022 from a medical oncology clinic within the Hawai’i Pacific Health system. Patient data collected include age at diagnosis of breast cancer, histology, BMI, clinical stage, sTILs, residual cancer burden, neoadjuvant treatment, and pathologic complete response. Core biopsy samples were processed and analyzed using the nCounter Breast Cancer 360 Panel. Further analysis was obtained using the nSolver Advanced Analysis Module. Results: Patient characteristics are listed in the table. Most patients had the basal-like immunosuppressed TNBC subtype. Among differentially expressed genes between races, 31 genes were statistically significant. NHPIs expressed more IL12RB2 and MYC, and Asians expressed more FGFR4 and MLPH. Among responders compared to non-responders, 5 genes were statistically significant. Responders expressed more STC1 and PTGER3, and non-responders expressed more CRAYAB, TMPRSS2, and CHAD. Among old and young patients, 132 genes were statistically significant. Older patients expressed more FUT3 and CKMT1, and younger patients expressed more MMP7 and MIA. Conclusions: In this pilot study, the molecular and genetic differences suggest that the tumor microenvironment may play a role in treatment outcomes between NHPIs and Asians. Further analysis will be conducted to determine the differences in immune cell infiltration. [Table: see text]
The efficacy of PARP inhibitors in the treatment of patients with synchronous breast cancer.
Authors: Izrailbekova Kamila , Kamishov Sergey , Saydullaev Sunnatilla , Niyozova Shakhnoza Khamoydinovna , Tillyashaykhov Mirzagaleb , Olimjonova Gulnoza , Sobitov Abdurakhmon 
Published: June 2024

e13041 Background: Currently, the role of BRCA1/2 in the development of primary and multiple malignant breast tumors is under discussion, along with the effectiveness of targeted therapy for this oncopathology. At the same time, there is a lack of sufficient research dedicated to the treatment of patients with synchronous breast cancer (BC) concurrent with ovarian cancer (OC) and the outcomes of using PARP inhibitors in this patient population. Methods: A retrospective analysis of treatment outcomes based on long-term survival indicators was conducted for 23 patients with synchronous BC, where the second tumor was OC. These patients underwent evaluation and treatment between 2017 and 2022. The average age of the patients was 45.3±5.6 years, with a prevalence of patients in stages IIb-IIIa of BC and IIb-IIIc of OC. Germline mutations in the BRCA1/2 genes were detected in 8 patients, among whom 5 exhibited the triple-negative phenotype of BC. The 1st group included 11 (47.8%) patients without BRCA1/2 mutations, who received neoadjuvant chemotherapy with paclitaxel 175 mg/m2 + carboplatin AUC 6 once every 3 weeks. In the 2nd group, consisting of 12 (52.2%) patients, olaparib 800 mg was added to this chemotherapy regimen. This group also included 8 patients with BRCA1/2 mutations. Results: In the majority of patients in both groups, a significant elevation in CA125 levels in serum was observed, averaging 563 U/mL, with practically normal CA153 levels at 32 U/mL. Identified mutations included 5382insC and 4154delA mutations in the BRCA1 gene, as well as the 6174delT mutation in the BRCA2 gene. Patients underwent three courses of treatment, and four weeks after completing the last course, surgical intervention was performed in the form of radical mastectomy, hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Following surgical treatment, patients received adjuvant chemotherapy following the same regimens. In the 2nd group, patients continued to receive olaparib for one year, and no signs of unacceptable toxicity were reported. The median overall survival in the first group of patients was 34.2 months (95% CI: 28.6-37.5), while in the second group, it was 36.8 months (95% CI: 31.4-41.1). The addition of bevacizumab significantly increased the median time to progression from 13.8 months (95% CI: 11.8-14.5) to 15.2 months (95% CI: 12.4-15.8), p=0.042. Lethal outcomes primarily occurred due to the progression of ovarian cancer. Conclusions: Thus, the addition of the PARP inhibitor olaparib to a platinum-based chemotherapy regimen in patients with synchronous breast cancer, associated with germline mutations in BRCA1/2 genes and the presence of ovarian cancer as a second tumor, has a positive impact on treatment outcomes. This contributes to the resectability of patients and significantly increases the median time to progression.
Prevalence of somatic PIK3CA mutations in hormone receptor-positive metastatic breast cancer: The Indian experience.
Authors: Goel Aastha , Gogia Ajay , Mathur Sandeep , Sasi Archana , Batra Atul , Deo S.V.S , Tanwar Pranay , Prasad Chandra Prakash 
Published: June 2024

e13047 Background: The phosphatidylinositol 3-kinase (PI3K) inhibitors have been found to improve survival outcomes in hormone receptor-positive metastatic breast cancer (MBC) and are FDA-approved in this setting after progression on hormonal therapy. However, real-world data from India on the prevalence of PIK3CA mutations is scarce. Methods: This is a retrospective study including patients with hormone receptor-positive breast cancer registered at our center between January 2017- and December 2023 who developed metastatic disease on follow-up after getting appropriate treatment (adjuvant /neoadjuvant) as per institutional protocol. The PIK3CA mutation testing was done on the biopsy specimen. FDA-approved therascreen PIL3CA RGQ PCR kit from Qiagen was used and the assay is a real-time qualitative PCR test for the detection of 11 mutations phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene (Exon 7: C420R; Exon 9: E542K, E545A, E545D [1635G>T only], E545G, E545K, Q546E, Q546R; and Exon 20: H1047L, H1047R, H1047Y) using genomic DNA (gDNA) extracted from formalin-fixed, paraffin-embedded (FFPE) breast tumor tissue. The clinical demographics of patients with PIK3CA mutations were extracted from the hospital database and represented descriptively. Results: A total of 80 consecutive patients with hormone-positive breast cancer at relapse were screened and 26 were found to have PIK3CA mutations (32.5%) of which 24 were female (92.3%). The median age of patients with mutated PIK3CA cases was 50 years (range: 31 to 72 years). The clinical stage of disease at presentation was: stage II in 11.5%, IIIA in 23.1%, and IIIB in 65.4% of cases. The median time of relapse was 21 months from diagnosis (range: 10 to 42 months). The disease sites at relapse were multiple in 23 patients (88.46%) [including central nervous system (CNS) relapse in 3 patients) and CNS (brain) only in 3 patients (11.54%). The mutations detected included H1047R (3140A>G at exon 20) in 8 cases, E545K (1633 G>A at exon 9) in 5 cases, Q546R (1637 A>G at exon 9) in 4 cases, E542K (1624 G>A at exon7) in 3 cases and synchronous mutations (E542K/E545K at Exon 7) in 3 cases and (H1047R/H1047L at exon 20 ) in 3 cases. Only eight patients received alpelisib with fulvestrant due to financial constraints. Conclusions: This is the first Indian study that describes the prevalence of PIK3CA mutations in hormone-positive breast cancer at relapse. Around one-third of patients harbor this mutation and 23.1% of cases have CNS involvement at relapse. The most common PIK3CA mutation detected was H1047R (exon 20) followed by E545K (exon 9).
Risk predictors as companion diagnostics for ER positive, HER2 negative early staged breast cancers from India.
Authors: Ramshankar Vijayalakshmi , Gopalakrishnan Aravinda lochan , Krishnamurthy Arvind , Radhakrishnan Venkatraman , Iyer Priya 
Published: June 2024

e13049 Background: Gene expression profiling tests can identify women with breast cancer most likely to benefit from chemotherapy providing accurate prognostic information than other non-genetic clinicopathological parameters. These derive specific molecular features of a tumour indicating an increased likelihood of rapid growth, metastasis risk, and response to chemotherapy. The tests are typically performed after surgery, in conjunction with other available information such as tumour size and grade. The objective of the current study was to evaluate the risk prediction as a companion diagnostic assay for women with early staged breast cancers (ER+,HER2-ve). Methods: The risk prediction was done evaluating quantitative gene expression profiling on Nanostring nCounter Flex platform using total RNA extracted from FFPE tissues (n = 81) obtained from trucut biopsy tissues and post MRM specimens after ensuring the tumour representation. The gene quantitations were derived after normalisation and using nSolver and Roselind software based statistical analysis. Results: We found 55.5% (45/81) and 44.5% (36/81) to be of intrinsic subtype Luminal A and Luminal B among our breast tumours respectively. The risk of recurrence score was high for luminal B (36.1% ; 13/36) compared to luminal A (13.4% ; 6/45). There was no difference pertaining to the Tumour Inflammation score (TIS score) among the luminal A and B that depicted good response to immunotherapy with 80% (36/45) among the luminal A and 72.3% (26/36) among the luminal B. We have identified top 38 differentially expressed genes that drive the high breast cancer proliferation score among the breast cancers in Indian women. The top 5 genes influencing the risk of recurrence with high BCP among the luminal A tumours were GNLY, CHRNA5, CDC20, MELK, RRM2 and among luminal B we got FGFR2, AURKA, MYBL2, CCNE2 and UBE2C. The top genes combining both types influencing the genomic risk of recurrence were FGFR2, MYBL2, AURKA, TTK, UBE2c and ORC6. The genomic risk of recurrence is based only on the gene expression unlike the risk of recurrence which includes the tumour size and nodal involvement. The top genes influencing a poor response to immunotherapy among luminal A was CNTFR, HAPLN1, FGF12, COL4A6 and CDH2 and the top genes influencing poor response to immunotherapy among luminal B was FGFR2, MYCN, AURKA and FAM198B. Conclusions: This is the first study from India using risk prediction test as a companion diagnostics assay for ER+ HER2-ve early staged breast cancer. The salient genes important to drive the breast cancer proliferation increasing the risk of recurrence scores in both luminal A and Luminal B intrinsic subtypes have been derived. We can validate these gene signatures as smaller panels of tests that can be low cost and more suitable for LMIC like India. The BCP panel of genes were relevant driving the recurrence.
Evaluating the impact of GLP-1 receptor agonists on weight management in patients with breast cancer undergoing endocrine therapy: A comparative analysis.
Authors: Urueta Portillo Daniela , Mazo- Canola Marcela , Alhaj Sara 
Published: June 2024

e13063 Background: Obesity has been linked to increased risk of recurrence in postmenopausal patients with history of Hormone Receptor positive + (HR) breast cancer. making weight management very important in this patient population. The use of endocrine therapy with aromatase inhibitor (AI) or selective estrogen modulators (SERM) in this population has been linked to weight gain (PMID: 37831449). This study evaluates the effectiveness of GLP-1 medications (Semaglutide, Liraglutide, Dulaglutide, Tirzepatide) in these patients, comparing weight loss outcomes to those in non-cancer populations. Methods: A retrospective analysis was conducted on breast cancer patients who were receiving endocrine therapy (AI or SERM) in combination with GLP-1 medications. The study primarily focused on evaluating mean baseline Body Mass Index (BMI), the proportion of patients with a BMI ≥30, and the mean percentage change in BMI at the 12-month mark, including 95% confidence intervals (CIs) for these changes. Results: The study found that the mean percentage changes in BMI at 12 months for the GLP-1 medications were as follows: Semaglutide resulted in a -4.34% change (95% CI [-7.66%, -1.02%]), in stark contrast to a -14% change reported in the general population (PMID: 33567185); Liraglutide showed a -3.51% change (95% CI [-8.48%, 1.45%]), compared to -8.4% (PMID: 26132939); Dulaglutide led to a -2.33% change (95% CI [-6.80%, 2.13%]), against -10.0% (PMID: 34189841); and Tirzepatide recorded a 2.31% change (CI [-11.47; 20.54]) relative to -15.0% (PMID: 35658024). These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population. Conclusions: The study concludes that breast cancer patients on endocrine therapy exhibit less significant weight loss with GLP-1 medication treatment than what has been observed in the general population. This suggests that endocrine therapy may reduce the weight-loss efficacy of GLP-1 medications in this particular patient group. Further prospective research is essential to elucidate the mechanisms behind this attenuated response and to develop effective weight management strategies tailored for breast cancer patients undergoing endocrine therapy.
The impact of vitamin D levels on the progression-free survival of women with hormone receptor-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors.
Authors: Aranda-Gutierrez Alejandro , Meraz-Brenez Andres , Gonzalez-Sanchez Hector Raul , Verduzco-Aguirre Haydee Cristina , Martinez-Cannon Bertha Alejandra 
Published: June 2024

e13075 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) halt the transition from the G1 to the S phase, a process governed by the hyperphosphorylation of the retinoblastoma (Rb) protein. Similarly, vitamin D3 has been demonstrated to induce cell cycle arrest through the inhibition of various cyclin-dependent kinases, including those responsible for phosphorylating the Rb protein. Therefore, we hypothesized that suboptimal vitamin D levels may compromise the efficacy of CDK4/6i used to treat hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). Methods: We conducted a retrospective single-center study of women diagnosed with HR-positive, HER2-negative MBC and treated with any CDK4/6i between 2020 and 2023. Eligible patients were those who received at least one cycle of CDK4/6i, had a baseline 25-OH vitamin D measurement, and had a follow-up period of more than three months. Independent samples T-test, X2, and Fisher’s exact tests were used to evaluate associations between variables. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and compared according to vitamin D levels using the log-rank test. Results: Among 31 patients, the mean age at diagnosis was 53 years (SD 14), 24 (77%) received CDK4/6i in the first-line setting, and 9 (29%) had suboptimal vitamin D levels (<20 ng/ml). Clinicopathological features based on vitamin D levels are shown (Table). The type of iCDK was different according to vitamin D levels (p = 0.036), with no other observed differences between groups. With a median follow-up of 26 months (95% CI 17-35) since iCDK initiation, median PFS was not reached for the entire cohort. A univariate analysis revealed that patients with suboptimal vitamin D levels had an inferior median PFS compared to patients with optimal levels (14 months [95%CI 4-24] vs. not reached [p=0.016]). Notably, no other parameter was associated with PFS in univariate analyses. Conclusions: In this cohort of Mexican patients with HR-positive, HER2-negativeMBC, suboptimal vitamin D levels adversely impacted PFS. Given the retrospective nature of this study and the limited number of patients, we emphasize the importance of studying these findings prospectively. [Table: see text]
Real-world comparison of the efficacy of three CDK4/6 inhibitors (CDK4/6i) in the first-line treatment of endocrine-sensitive advanced breast cancer (aBC): Single institution experience.
Authors: Dedic Plavetic Natalija , Čular Katarina , Gudelj Dora , Kaceljak Kristina , Križić Marija , Popovic Marina , Bulimbašić Stela , Sirotković-Skerlev Maja , Bubanović Sanda , Silovski Tajana 
Published: June 2024

e13080 Background: The combination of CDK4/6i and endocrine therapy (ET) is the standard of care in the first-line treatment of hormone receptor positive (HR+), HER2- aBC. In registrational studies, the progression-free survival (PFS) of all three CDK4/6i ranged from 23.8 to 28.12 months and overall survival (OS) from 53.9 to 66.8. In Croatia, both ribociclib and palbociclib were approved for clinical use in August 2018 and abemaciclib in November 2019. Methods: This retrospective study included patients with endocrine-sensitive HR+, HER2- aBC treated with aromatase inhibitor (AI) and CDK4/6i in the first-line setting between August 2018 and October 2023 at University Hospital Centre Zagreb. Ethics committee approval was obtained before the study was commenced. Patient demographics, clinical presentation, tumor characteristics and treatment data were collected. Real-world PFS (rwPFS) and OS analyses were done with the final data cut-off date of December 31, 2023, using type 1 right censoring. Data were analyzed using the Kaplan-Meier method. Results: Of the 274 patients treated with a combination of CDK4/6i and ET in the first-line setting, 172 with endocrine-sensitive tumors (98 de novo metastatic and 74 with treatment-free interval longer than 12 months) were eligible for the study, of which 41.86% (72/172) received ribociclib, 44.19% (76/172) palbociclib, and 13.95% (24/172) abemaciclib. Overall rwPFS was 48 months (95% CI:35-53). In the abemaciclib group, median rwPFS and OS were not reached in the follow-up period. The rwPFS was 48 (95% CI:27-53) for ribociclib and 47 (95% CI:30-49) for palbociclib. The overall OS was 62 months (95% CI:47-62). Median OS in the ribociclib group was 62 months (95% CI:40-62) and in the palbociclib group 52 (95% CI:42-54) months. Conclusions: The PFS and OS results for palbociclib and ribociclib in this retrospective real-world study correlate with results from randomized clinical trials, confirming some inferiority of palbociclib compared to ribociclib in the context of OS. Due to the later availability of the drug, larger sample size and longer follow-up will be needed to make definitive conclusions on the efficacy of abemaciclib.
Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multicenter, open-label, single-arm, phase II study.
Authors: Peng Peijian , Xu Xiaolu , Zhong Jincai , Ye Jin-Hui , Wang Zhi-Hui , Wang Hong , Lin Hong , Du Caiwen , Zou Guorong , Ouyang Jie , Shi Ying-ying , Xu Fei , Yu Gengsheng , Lu Yongkui , Wang Yong-Xia , Cui Shi-En , Li Lu-Zhen 
Published: June 2024

e13139 Background: The combination of eribulin and gemcitabine has demonstrated a similar progression-free survival (PFS) benefit as paclitaxel plus gemcitabine, with less neurotoxicity, for patients with MBC who have not received prior cytotoxic chemotherapy. However, the effect of eribulin plus gemcitabine on PFS in second line or beyond remains unclear. Methods: This open-label, single-arm, phase II study (NCT05263882) was conducted at 14 institutions in China. Eligible patients had histologically confirmed HER2-negative MBC and had received at least one prior taxane-containing chemotherapy regimen for advanced disease, and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m2) and gemcitabine (1.0 g/m2) on days 1 and 8 of a 21-day cycle. Efficacy outcomes, including PFS, objective response rate (ORR), and disease control rate (DCR), were assessed using RECIST v1.1. Adverse events (AEs) were graded according to NCI-CTC version 5.0. Results: A total of 70 patients were enrolled from November 2021 to October 2023; 47 (71.4%) had HR+HER2- and 18 (28.6%) had triple-negative MBC. The median patient age was 50 years (range: 31-68), and the sites of metastasis were the bone (68.6%), liver (52.9%), lymph nodes (48.6%), lung (44.3%) and brain (10.0%). Patients had received a median of 3 prior lines of systemic treatment, 2 lines of chemotherapy, and 1 line of endocrine treatment. Among all patients, the ORR was 48.6%, the DCR was 92.9% and the median PFS was 7.2 months. For the HR-positive subgroup, the median PFS was 8.4 months, while for the triple-negative subgroup, it was 6.3 months. Among HR+ patients who had received prior CDK4/6 inhibitor treatment, the median PFS was 7.2 months. In the subgroup of HR+ patients who had not received CDK4/6 inhibitor treatment, the median PFS had not been reached. For the HR+ HER2-low subgroup, the median PFS was 8.4 months. The most common grade 3-4 AEs were hematological, including neutropenia (38.6%), leukopenia (31.4%), anemia (24.3%), and thrombocytopenia (15.7%). Grade ≥3 perceived AEs were relatively low. Conclusions: Eribulin plus gemcitabine was effective in heavily pretreated patients with HER2- MBC, while maintaining a predictable and manageable safety profile. Clinical trial information: NCT05263882 . [Table: see text]