bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of pathological response to neo-adjuvant chemotherapy using texture parameters of initial 18-FDG PET/CT in estrogen receptor positive/Her2 negative (ER+/HER2-) early breast cancer (eBC).
Authors: Corda Hugo , Lasla Hamza , Guillerminet Camille , Lacombe Marie , Girault Sylvie , Campone Mario , Frenel Jean-Sebastien , Jézéquel Pascal , Patsouris Anne 
Published: June 2024

e12567 Background: ER+/HER2- phenotype represents 70% of eBC and is itself a heterogenic entity in which neoadjuvant chemotherapy (NAC) can be indicated. Early change in 18F-FDG uptake on PET/CT, using standardized uptake value (SUV) parameter, has been shown as a predictive biomarker of response to NAC. However, this parameter can be defaulted in ER+/HER2- BC. The objective of this work was to evaluate the correlation of textural parameters of initial 18-FDG PET/CT with histologic response in ER+/HER2- eBC. Methods: All patients receiving NAC for ER+/HER2- eBC, with 18F-FDG PET/CT prior NAC at the Integrated Center for Oncology Pays de Loire were included between 2012 and 2023. Twenty-nine metabolic and volumetric parameters and 42 textural features (DOSISOFT software, Planet Onco v2.0) were collected. Pathological response was assessed for each breast tumoral lesion in case of multifocal disease. Results: A total of 161 patients with 179 lesions were included. Medium age was 51 years old. 89% and 10% of patients presented a cT1 or cT2 tumoral lesion, 78% with lymph node involvement, 44% with a grade 3 and 46% with a HER2 low status. 21% of patients achieved a pathological complete response in breast (ypT0) and 11% a complete histologic response (ypT0N0). Examinations were performed using three types of PET/CT systems (GE Healthcare and Philips Healthcare). In order to harmonize radiomics data Combat method was used. Thirteen semi-quantitative (MTV and SUVmax, SUVmean, SUVmean(EVPc), SUVpeak, TLG for weight-normalized and lean-body-mass-normalized, respectively) and 6 textural parameters (entropy, homogeneity, SRE, LRE, LGZE, and HGZE) were retained. For all radiomics features used in this study, no statistical difference was found between ypT0 and non-ypT0 patients (p ≥ 0.05). Conclusions: Selected textural parameters were not associated with histologic response in our cohort of ER+/HER2- eBC. However, many other textural features, not retained in this study because influenced by acquisition parameters and segmentation methods, could be taken into account. An ongoing preliminary work (as resampling, normalization) is needed to improve their robustness before evaluating their interest in predicting histologic response to NAC.
Change in tumor microenvironment and PD-L1 expression with rucaparib treatment in triple-negative breast cancer.
Authors: Halder Ritika , Bhamidipati Nitish , Kiss Alexi , Aldhahri Walaa , Ehsani Sima , Segar Jennifer Margaret , Foster Nova , Chalasani Pavani 
Published: June 2024

e12569 Background: Triple-Negative Breast Cancers (TNBCs) represent a diverse subset of tumors characterized by varied responses to therapies including immunotherapy (IO). While IO is approved in early-stage and advanced TNBC, responses are modest. Modulation of the tumor microenvironment to improve responses to IO is an active area of research. In-vitro and in-vivo studies have shown Poly-ADP Ribose Polymerase inhibitors (PARPi) to increase PD-L1 expression in sporadic, BRCA1 and BRCA2 mutated TNBC cell lines improving response to IO. In addition, TNBCs have diverse mechanisms leading to Homologous Recombination Deficiency and the role of PARPi in sporadic TNBCs is still unclear. Methods: To further investigate the role of PARPi in tumor immuno-modulation we conducted a single-arm, open-label, window of opportunity (WOO) trial in patients with early-stage TNBC (NCT03911453). This study was approved by our institutional review board. Patients with histologically documented stage I-III TNBC were eligible for definitive surgery were enrolled. Patients were treated with 600mg BID rucaparib for 21 days. Pre- and post-treatment tumor biopsies were collected. Post-treatment, patients went to surgery or proceeded with neoadjuvant chemotherapy (NAC) followed by definitive surgery. Our primary endpoint was to assess change in PD-L1 expression. In addition, change in tumor microenvironment was by evaluating change in percentage of B cells, T cells and macrophages was calculated. Results: Twenty patients were enrolled. Nineteen patients completed 21 days and 1 patient went on extended duration PARPi during the COVID19 pandemic. Almost 50% of patients went to surgery while the rest went onto NAC after PARPi therapy. Pre-treatment tumor samples were obtained from the diagnostic core biopsies while post-treatment, fresh frozen and Formalin Fixed Paraffin Embedded were obtained either at time of surgery or a research biopsy prior to NAC initiation. Primary biomarkers data was successfully done in 14 paired samples. Treatment with rucaparib has increased expression of PD-L1 from median of 15% in pre-treatment tumor samples to a median of 26% in post-treatment tumor samples. Table below summarizes our results. Conclusions: Our study revealed that treatment with PARPi, rucaparib, changed the tumor microenvironment as noted by changes in expression of PD-L1, and immune milieu in and around the tumor. This could lead to change in responsiveness to therapies including CKI. This strategy should be further investigated to evaluate improving responses to immunotherapies. Clinical trial information: NCT03911453 . [Table: see text]
Information and support needs of young Black women with early breast cancer to enable self-management and informed decisions during breast cancer treatment.
Authors: Weldon Christine B. , Steele Sue , Leach Virginia , Ravelo Arliene , Trosman Julia R. 
Published: June 2024

e12587 Background: Black women with breast cancer are more likely to experience care delays and worse outcomes than White women (Emerson, Cancer ’20). Patient self-management contributes to more timely cancer care delivery and improved outcomes. We interviewed young black women with breast cancer to explore information needs related to their self-management interests and obtain feedback on the independent use of self-management tools developed within the 4R Oncology model. 4R (Right Info/Care/Patient/Time) is an approach to facilitate patient self-management using a Care Sequence plan- a care checklist with a visual depiction of timing and sequence of care, as well as a side effect self-care tool. These tools are typically provided in the clinic, but we aimed to explore if they could be used independently by patients. Methods: The interviewee cohort (N=20) was recruited from the Tigerlily Foundation ANGEL (Advocate Now to Grow, Empower and Lead) patient program. The cohort included Black women, average age 36 (21 to 46), stage I-III breast cancer. The framework approach of qualitative research was used. Results: All women reported information needs not addressed by their providers. Mental wellness and social support information were lacking for 70% (“I never worked with a social worker or anyone to support my mental health”). Most women (65%) wanted more information about breast cancer surgery options and post-surgery drains, bras, pain, and tingling (“before I had my surgery, my doctor didn't tell me all the options I had”). 40% mentioned a lack of reconstructive option information, including how radiation affects implants, “risk of encapsulation” and the long-term impact of having implants “changing them out every 10 years.” A slight majority (55%) desired nutrition and integrative medicine information. About one-third (35%) of women mentioned considerable skin issues during radiation treatment (“I needed skin care, for people with darker skin”). When reviewing a Care Sequence and a side-effect self-care tool, 95% reported they would use them independently if their clinic did not provide them ("I just got general information about breast cancer, I would have preferred a step-by-step process like this"; “This describes what services each role provides, and links to more support”). Most (95%) would have used the side-effect tool ("My chemo education was overwhelming, just a bunch of info thrown at me all at once, having a resource to look at would have been helpful"). Conclusions: In interviews with young Black women with breast cancer we found several information needs and a preference for tools to support self-management during treatment. These indicate considerable improvements are needed in this area. Using the input from the interviews, we are enhancing the 4R Oncology tools to better support the needs of Black patients with breast cancer.
The relationship between PIK3CA mutations and survival in patients with human epidermal growth factor receptor 2–positive breast cancer receiving pyrotinib combined with trastuzumab for neoadjuvant treatment.
Authors: Shi Qiyun , Tian Hao , Ma Dandan , Xuhong Juncheng , Ge Jia , Liu Feng , Lan Yang , Tang Peng , Liang Yan , Chen Li , Fan Linjun , Zhang Yi , Luo Tao , Bian Xiuwu , Jiang Jun , Qi Xiaowei 
Published: June 2024

e12637 Background: Our previous study suggested that HER2-positive breast cancer patients with activated mutations in PIK3CA are less likely to achieve a pathological complete response (pCR) from pyrotinib combined with trastuzumab in the neoadjuvant setting. The relationship of PIK3CA mutations and survival remains unknown. Methods: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between PIK3CA mutations and event-free survival (EFS) and overall survival (OS) were explored. Results: Among the cohort of 50 cases, five patients dropped out during treatment due to various reasons, whereas the other 45 patients were followed up until August 31, 2023. The median follow-up was 36.1 months, and mEFS and mOS were not reached yet. Kaplan-Meier estimated 3-year EFS rate and OS rate were 91.1% (95% confidence interval [CI]=83.2%-99.8%) and 97.1% (95% CI=91.8%-100%), respectively. Patients with wild-type PIK3CA tended to achieve a better 3-year EFS rate (96.2% vs 63.2%, hazard ratio [HR]=0.18, 95% CI=0.02-1.59, log-rank P = 0.081) compared with the patients with mutated PIK3CA. Besides, patients with pCR showed a better 3-year EFS rate (96.2% vs 84.2%, HR=0.16,95% CI=0.02-1.45, log-rank P = 0.063) compared with the patients without pCR. Conclusions: HER2-positive breast cancer patients with activated mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab in the neoadjuvant setting, but this conclusion still needs to be confirmed by large-sample studies and long-term follow-up results. Clinical trial information: 1900022293.
Effect of HER2-low expression on the efficacy of CDK4/6 inhibitors in breast cancer: A meta-analysis.
Authors: Ye Lingling , Dai Yan , Chen Liushan , Liang Yuqi , He Jiafa , Chen Shenying , Song Xue , Luo Wei , Xu Rui , Chen Qianjun 
Published: June 2024

e13034 Background: The effect of human epidermal growth factor receptor 2 (HER2)-low expression on the efficacy of CDK4/6 inhibitors in breast cancer is unclear. Therefore, the aim of this meta-analysis was to determine the effect of HER2-low on the efficacy of CDK4/6 inhibitors in advanced breast cancer. Methods: We searched 10 databases and meeting minutes up to July 15, 2023, to identify studies that reported median progression-free survival (mPFS) and overall survival (OS) among HR+/HER2-low breast cancer patients and HER2-zero breast cancer patients receiving treatment with CDK4/6 inhibitors. We calculated pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 9 retrospective studies involving 1494 patients were included. HER2-low breast cancer patients accounted for 52.48% of the sample, and HER2-zero breast cancer patients accounted for 47.52% of the sample. The mPFS was significantly worse for HR+/HER2-low breast cancer patients treated with CDK4/6 inhibitors combined with endocrine therapy than for HER2-zero breast cancer patients (risk ratio = 1.29, 95% CI: 1.15-1.44, p < 0.00001). There was no significant difference in the median overall survival (mOS) between patients with HER2-low breast cancer and patients with HER2-zero breast cancer (risk ratio = 1.07, 95% CI: 0.69-1.66%, p = 0.78). The mPFS was significantly worse for HR+/HER2-low breast cancer patients receiving first-line treatment with CDK4/6 inhibitors combined with endocrine therapy (risk ratio = 1.25, 95% CI: 1.07-1.47, p = 0.0002). Conclusions: The mPFS of patients with advanced HER2-low breast cancer and first-line salvage patients receiving CDK4/6 inhibitors combined with endocrine therapy was significantly inferior to that observed in HER2-zero breast cancer patients. However, there were no discernible differences in the mOS between the two patient groups.
Real-world experience with CDK4/6 inhibitors in the first-line palliative setting for HR+/HER2- advanced breast cancer.
Authors: Patel Ram , Nasser Abdullah 
Published: June 2024

e13066 Background: CDK4/6 inhibitors paired with aromatase inhibitors (AIs) have redefined the first-line treatment for metastatic breast cancer, as evidenced by several pivotal trials. Although progression-free survival (PFS) has been consistent across these studies, notable differences in overall survival (OS) have been observed. Our study evaluates the real-world efficacy of palbociclib and ribociclib, in combination with AIs, for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer at our institution. Methods: We retrospectively reviewed charts of adult patients with advanced metastatic breast cancer at a single academic center from January 1, 2015, to December 1, 2022. We extracted relevant clinical data to estimate the median PFS and OS associated with palbociclib and ribociclib. Results: Among 75 patients analyzed, the majority were female (98.7%) and postmenopausal (77.3%). Palbociclib was prescribed to 74.7%, while 52.0% presented with de novo stage IV disease. Those on ribociclib were significantly younger (median age 57.6 vs. 67.5 years; p = 0.013) and more likely premenopausal (42.1% vs. 5.4%; p < 0.001). Median PFS for palbociclib was 20.3 months (95% CI: 14.8-46.0), with an OS of 37.2 months (20.3 months to not reached). Median PFS and OS for ribociclib were not reached. The differences in PFS and OS between the drugs were not statistically significant (PFS log-rank p = 0.1; OS log-rank p = 0.2). Conclusions: Our real-world analysis suggests a non-significant trend towards improved PFS and OS for ribociclib over palbociclib when used with AIs for treating HR+/HER2- advanced breast cancer, potentially influenced by the younger age of patients on ribociclib. Further research with larger cohorts and extended follow-up is warranted to substantiate these observations.
Clinical utility of an ultra-sensitive ctDNA NGS assay for the detection and monitoring in HR-positive, HER2-negative breast cancer.
Authors: Liao Hao , Zhong Jianxin , Liu Xiao-ran , Bin Shao , Tang Haoran , Jia Cancan , Xie Feng , Zhang Yue , Jia Shidong , Li Huiping 
Published: June 2024

e13076 Background: Breast cancer is the most diagnosed cancer in women globally, mainly as hormone receptor HR-positive, HER2-negative. While endocrine therapies have markedly improved clinical outcomes, the threat of disease progression persists. This study introduces an ultra-sensitive circulating tumor DNA (ctDNA) Next-Generation Sequencing (NGS) assay that was designed for in-depth genomic profiling of breast cancer patients undergoing endocrine therapy, aimed at detecting treatment resistance and monitoring disease progression. Methods: In this ongoing investigation, 46 patients with advanced HR-positive, HER2-negative breast cancer were enrolled, and plasma samples were collected subsequent to first-line aromatase inhibitor (AI) treatment and before the initiation of second-line treatment with fulvestrant. The study employed the PredicineCARE ULTRA, an ultra-sensitive liquid biopsy assay with a proprietary NGS panel and exceeds 100,000x coverage, allowing for the ultra-sensitive identification of genomic alterations, surpassing the detection capabilities of standard ctDNA NGS assays with approximately 20,000x coverage. Results: Within the cohort of 46 patients, the ultra-sensitive assay detected 193 somatic mutations, 95 gene copy number variants (CNVs), and a gene fusion involving FGFR3. The most commonly mutated genes, with a prevalence of 20% or more, were TP53 (33%), PIK3CA (26%), ATM (24%), ESR1 (22%), and BRCA2 (20%). These findings were benchmarked against results from a down-sampling algorithm designed to emulate ctDNA assays with 20,000x coverage. The ultra-sensitive assay revealed 31.3% more mutations (193 vs. 147) and 30.1% more CNVs. It was especially proficient in detecting mutations with allele frequencies (MAF) below 0.1%, identifying 10 additional mutations not observed at the standard ctDNA assay sensitivity, with the lowest MAF detected being 0.03% compared to the 0.1% threshold of the standard assay. This heightened sensitivity was evident in genes associated with targeted therapies and drug resistance, identifying 30.7% more variations in PIK3CA and 11.1% more in ESR1, with the lowest MAFs of 0.08% and 0.06%, respectively. The FGFR3-BAIAP2L1 gene fusion was also uniquely detected by the ultra-sensitive assay, with a MAF of 0.09%. Conclusions: The ultra-sensitive ctDNA NGS assay demonstrated superior detection of low-frequency mutations in HR-positive, HER2-negative breast cancer, significantly outperforming standard liquid biopsy assays. This enhanced sensitivity may offer profound implications for identifying more diagnostically positive patients who may benefit from targeted therapy such as PIK3CA and ESR1 inhibitors. This ultra-sensitive ctDNA assay will also enable early detection of treatment resistance and refined disease monitoring, potentially guiding more effective personalized therapies.
Single institution retrospective review of patients with metastatic hormone receptor positive breast cancer receiving first line therapy of CDK4/6 inhibitors.
Authors: Bhargava Anika , Tavcar Michelle , Dong Brian 
Published: June 2024

e13090 Background: Breast cancer continues to be the most commonly diagnosed cancer in women. The majority of these cancers are estrogen positive (ER+) and about 6% of new cases are stage 4 at time of diagnosis. The current standard of care for postmenopausal women with stage 4 ER+ breast cancer is a combination of an aromatase inhibitor (AI) with a cyclin-dependent kinase (CDK) 4/6 inhibitor. Based on Medicare data claim analysis from IQVIA, CDK 4/6 inhibitors are being used nationally in the first line setting in 56% of cases where 24% of cases were treated with AI monotherapy. The state of Kentucky currently lies below this national average by using this treatment regimen in 38% of cases where 47% of cases are treated with AI monotherapy. The reason for this discrepancy between the national average and Kentucky is currently unknown. To further understanding, we have conducted an internal review of adherence to the guidelines. Methods: This is a single center retrospective study done at University of Louisville, Brown Cancer Center. Data was collected on patients who had biopsy proven metastatic hormone positive breast cancer from July 2021 until May 2023 (n=41). Collected characteristics include age on diagnosis, tumor grade, sites of metastatic disease, first line treatment received, choice of CDK4/6 inhibitor if received, and prior exposure to chemotherapy or anti-estrogen therapy. Results: In our cohort of 41 patients, we found that 63.4% (n=26) of patients received an AI and CDK4/6 inhibitor in the first line. There were 4.88% (n=2) of patients who received AI monotherapy, 21.9% (n=9) received Fulvestrant and CDK4/6 inhibitor, 4.88 % (n=2) received AI and Fulvestrant and 4.88% (n=2) received Fulvestrant alone. In total, patients who received estrogen therapy plus CDK4/6 inhibitor totaled 85% of new patients (n=35). Conclusions: This internal review showed our institution to be compliant with endocrine therapy and CDK 4/6 inhibitor in front-line treatment for the majority of metastatic ER+ patients. Given the supportive data for use of CDK 4/6 inhibitors in front-line treatment, the compliance is expected to be much higher. We recommend continued discussion amongst oncology providers to help identify barriers to treatment and determine the causes for poor compliance in the state of Kentucky.
Fulvestrant and elacestrant utilization on prognostic outcome of patients with HR+ve/HER2-ve MBC.
Authors: Dawood Shaheenah S. , Hernández Gema , Segovia Alba 
Published: June 2024

e13094 Background: OS of pts with HR+ve/HER2-ve MBC has improved with CDK4/6i and endocrine therapy. Fulvestrant (FUL) works post progression on aromatase inhibitors in an endocrine resistant cohort. Ealcestrant (ELA) improves PFS compared to FUL in pts with an ESR1 mutation. This retrospective analysis looks at the trends in use of and associated outcome with FUL and ELA among pts with HR+ve/HER2-ve MBC. Methods: We utilized a federated network of de-identified health data representing approximately 135 million pt lives available through the TriNetX Research Network. We identified 14,387pts with HR+ve/HER2-ve MBC treated with endocrine therapy and CDK4/6i diagnosed between Nov 2018 - Nov 2023. OS was computed using the Kaplan Meier product limit method. Results: Mean age was 66 yrs. 5,736(39.9%) pts received FUL and 143(1%) pts ELA. In 2023 median time to use of FUL was 16m to 18m from metastases and median time to use of ELA decreased with time from 50m to 28m. Among pts who received ELA 65% received CDK4/6i for > 12m, 47% received FUL prior ELA, 7% received FUL after ELA. 5-yr OS of the whole cohort was 56.9%. 5-yr OS among pts who did and did not receive ELA was 85.4% and 60.0% respectively (HR 0.28, 95%CI 0.15-0.49, p<0.0001). 5-yr OS among pts who did and did not receive FUL w/o ELA was 61.5% and 60.9% respectively (HR 0.87, 95% CI 0.81-0.94, p<0.0001). 5-yr OS was 85.4% and 52.4% among pts who received ELA and FUL w/o ELA respectively (HR0.23, 95% CI0.14-0.41, p<0.0001). 5-yr OS was 88.7% and 67.9% among pts who received ELA and FUL w/o ELA respectively for > 3m (HR 0.29, 95% CI 0.05-1.145, p=0.11). Among pts who received CDK4/6i > 12m 5-yr OS was 86.0% and 64.9% among pts who received ELA and FUL w/o ELA respectively (HR 0.36, 95% 0.20-0.67, p = 0.0007). Among pts who received ELA 1-yr OS from the start of ELA was 86.0% and 33.3% among pts who received CDK4/6i>12m and < 12m respectively (p=0.72). Conclusions: To our knowledge this is the first real world data set to show the efficacy of ELA among pts with HR+ve/HER2-ve MBC who had progressed on endocrine therapy and CDK4/6i. Our results show decreasing time to use of ELA with improved outcome compared to FUL especially among pts who received CDK4/6i for > 12m. We continue to collect data among pts who are receiving ELA and expect over 200pts at the time of the presentation.