bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can high Ki67 predict distant recurrence in early-stage breast cancer with low Oncotype Dx score?
Authors: Fallah Parvaneh , Mulla Nasser Khleel , Aloyz Raquel , Aleynikova Olga , Florea Anca , Pelmus Manuela , Panasci Lawrence C. 
Published: June 2021

e12561 Background: Ki-67 is a marker of proliferating cells. The recurrence score based on the 21-gene breast cancer assay also called Oncotype Dx provides prognostic and predictive information for recurrence in early stage breast cancer patients. We previously showed that there is a moderate correlation between Ki67 and oncotype Dx recurrence score. In this retrospective study, we aimed to examine whether high Ki67 could predict the distant recurrence in early stage breast cancer with low oncotype Dx scores ( < 25). Methods: This retrospective study included 278 consecutive cases of hormone receptor-positive, HER2 negative (T1-2 N0 M0) breast cancer who were diagnosed between 2008 and 2015 with low oncotype Dx ( < 25). Patients’ clinical outcome in terms of distant recurrence after breast surgery was determined up to December 2020 (median follow-up of 7 years). Patients were divided in to low risk (Ki67 < 15%) and high risk (Ki67 > = 15%) groups. Results: Of 278 cases with average and median age of 59 and 60 respectively, 148 (53%) were in Ki67 low risk and 130 (47%) were in Ki67 high risk group. Average and median oncotype Dx were 13.86 and 15 respectively in Ki67 low risk versus 15.23 and 16 respectively in Ki67 high risk group. 13 patients (4%) experienced distant metastasis in lung, liver, bone and skin. Of these 13 cases with average and median oncotype Dx 15.84 and 19 respectively, 12 (92%) were in the Ki67 high risk group and only 1 (8%) belonged to the low risk category. High Ki67 patients were overrepresented in group with recurrent distant metastasis compare to group without recurrent disease (Pearson Chi-Square = 51.18 with 1 degree of freedom and P = < 0.001). Conclusions: Ki67 high patients in the low risk oncotype Dx group are relapsing at a significantly higher rate suggesting that Ki67 combined with low oncotype Dx further refines the risk of distant relapse.
Creation of a primary breast cancer culture repository from patients with a BMI >30 kg/m2: A Mexican endeavor.
Authors: Shveid Gerson Daniela , Zentella - Dehesa Alejandro , Gerson Cwilich Raquel , Rodriguez Benigno , Serrano Villamayor Omar , Villegas Osorno Diana Alejandra , Enciso López Ervin Saúl , Camarin Sanchez Efrain Isaias , Noguez-Ramos Alejandro , López Zepeda Lorena , Villalobos Alberto , Olivares Guillermo , Martínez-Herrera José Fabián 
Published: June 2021

e12574 Background: Currently there are no primary cultures or cell lines derived from patients with breast cancer and obesity. It has been postulated that breast cancer in obese women behaves differently as it does in non-obese women, as is composed of distinct biological features, as was generated in a different metabolic environment, as well as pertains to a different prognosis and different response to chemotherapy, lower rates of overall survival and a greater probability of recurrence. By creating a primary breast cancer culture bank of breast cancer tumors from women with obesity (BMI > 30kg/m2), we will establish a cell line exclusive to obese women in Mexico, where targeted therapy may be tested and treatment may be individualized depending on the characteristics of the patient. Methods: This study recruited 32 women with breast cancer and a BMI > 30 kg/m2, matched by 6 controls with are non-obese women with breast cancer. Elegibility criteria was determined by women with breast cancer confirmed by pathology, who had not been subjected to prior treatment regarding the neoplasm. The breast cancer removing surgeries and the patients were selected from the ABC Medical Center in Mexico City and all procedures were approved by the research and ethics committee of the hospital in question. Results: Through extensive communication a cooperative protocol was established between the departments of surgery, oncology, pathology and nursing to coordinate efforts and be able to take a 2 – 5 mm sample of the breast tumor removed from the patient. To be able to distinguish cancer cells from non-cancer cells (epithelial cells, fibroblasts, adipocytes) the Hayflick limit was be utilized. Once a primary breast cancer culture was established, 12 million cells will be injected into the subscapular area of athymic, nu-nu mice to be able to monitor tumoral growth in vivo and conduct a subsequent cellular analysis, determining it still pertains to the same characteristics of the tumor from which it was obtained. Conclusions: A primary breast cancer culture repository from patients with a BMI > 30 kg/m2 was established. This is the first primary breast cancer culture for both Mexican and obese women with breast cancer, the first in vitro method of analysis of specific characteristics typical of the Mexican population. Translational research may now be conducted on these new tumoral cultures to create individualized therapy for women with the distinct, aforementioned characteristics.
Aesthetic outcome and patient’s quality of life in breast cancer patients undergoing mastectomy with or without immediate reconstruction.
Authors: Afzal Sidra , Parvaiz Asad , Javed Nida 
Published: June 2021

e12587 Background: : Although post mastectomy Immediate breast reconstruction has shown to improve physical and psychosocial well-being of breast cancer patients, this is not a usual procedure in Pakistan due to limited resources and lack of awareness. The aim of our study is to evaluate patient’s satisfaction/ aesthetic outcomes between the patients undergoing mastectomy alone (Group A) and the ones undergoing mastectomy followed by immediate reconstruction (Group B). Methods: This is a prospective study conducted at Shaukat Khanum Hospital Pakistan comparing aesthetic outcome, patient’s satisfaction and Quality of life between two groups using Breast Q module. All patients undergoing mastectomy with and without reconstruction between April 2017 to July 2019 are included. Sample size of 84 was calculated (42 in each group). Results: The mean Q score of satisfaction with the breast in group B is 82.64 and in group A is 35.82 (P = 0.001). The mean Q score of Psychosocial well-being in group B is 89 vs 44.95 in group A (P = 0.001). The mean Q score of Physical well-being in group B is 98.23 vs 90.41 in group A (P = 0.002). The mean Q score of sexual well-being in group B is 81.93 vs 43 in Group A (P = 0.001). [Mean difference in score of 5-10 - little change, 10-20 - moderate change, > 20 - significant change].The mean difference between two groups in satisfaction with breast , psychosocial well-being and sexual well-being is more than 20 with a statistically significant p-value, while in physical well-being the mean difference is 7.8 which falls in little change group. Conclusions: Our study shows that reconstruction helps breast cancer patients in providing comprehensive care in a manner that they achieve a higher satisfaction with their appearance, psychological and sexual well-being without compromising oncological safety and this should be practiced more in our country. Also patients education about these procedures should be raised to help them fighting against this disease
Micro-organospheres: An automated patient-derived model platform for rapid drug screening of breast cancer.
Authors: Wang Zhaohui , Cortes-Sanchez Emilio , Yang Chieh-Hsiang , Nelson Daniel , Delubac Daniel , Hsu Shiaowen David , Welm Alana , Shen Xiling 
Published: June 2021

e12628 Background: Patient-derived breast cancer (BC) organoids are valuable preclinical models to study patient drug responses, demonstrating good correlations with patients’ clinical outcomes. However, establishment and expansion of such organoids from patient tumors for drug screening is currently a time-consuming and labor-intensive process. A more rapid and high-throughput method will enable broader utility in diagnostics and drug development. Methods: An automated, rapid and scalable microfluidic platform was used to process and develop BC micro-organospheres. Drug sensitivities studies on BC micro-organospheres were performed on day 3 and day 6 using 10-FDA approved drugs, including palbociclib, adriamycin, 5-FU, gemcitabine, methotrexate, everolimus, paclitaxel, docetaxel, ixabepilone, and vinblastine. The responses of micro-organospheres and organoids to the drugs were assessed by CellTiter 3D Glo assay on day 6 after the drug treatment. The growth and establishment of the micro-organospheres by imaging. The drug sensitivity and resistance of the micro-organospheres were analyzed by calculating the percentage cell viability and normalized growth rate inhibition (GRI) and compared to organoids. Results: We successfully established micro-organospheres from eight patient-derived BC organoids with a 100% success rate. The micro-organospheres preserved similar cell morphologies to the bulk organoids. 7/8 micro-organosphere models had similar drug response patterns to organoids between day 3 and day 6 as evident by the GRI heatmap. Specifically, we treated matching micro-organospheres and conventional organoids from two patients with 10 frontline BC chemotherapy drugs, and both showed similar response patterns with GRI heatmap. For the other 6 patient-derived models, the responses of micro-organospheres to docetaxel and everolimus also matched the historical drug responses of in bulk organoid culture with similar GRI heatmap. Conclusions: We have now shown the feasibility of establishing micro-organospheres as a rapid, scalable, and cost-effective platform to study patient-derived BC drug response. This technology has the potential to be used for both diagnostics to guide patient treatment and as a screening platform for new BC drug discovery.
Pyrotinib in the treatment of women with advanced HER2 positive breast cancer: A multicenter, prospective, real-world study.
Authors: Feng Jifeng , Zhang Lili , Wu Xiaohong , Zhou Jun , Zhu Mingzhen , Zhang Yusong , Yu Hao , Han Zhengxiang , Guo Yujiang , Guan Xiaoqing , Wang Xufen 
Published: June 2021

e13012 Background: Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy of pyrotinib in patients with different baseline characteristics in the actual clinical practice has been rarely reported. This study analyzed the efficacy and safety of pyrotinib in the real world. Methods: Patients with histologically confirmed advanced HER2 positive breast cancer were included in the analyses. All patients received pyrotinib-based therapy were given pyrotinib once a day in a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included adverse events (AE), objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results: A total of 132 patients (median age: 52 years [29-78]) were enrolled from February 2019 to March 2020. 94(71.21%) patients had visceral metastatic lesions and 20 (15.15%) had brain metastases. HR+, HR-, or unknown HR status for primary tumor accounted for 56.82%, 42.42%, 0.76%, respectively. 115(87.12%) patients were previously administered with trastuzumab. 96(72.73%) patients received pyrotinib-based therapy as a second or further line of treatment. 94(71.21%) patients initiated pyrotinib treatment at 400 mg. Treatment regimens were pyrotinib plus capecitabine (55.30%), pyrotinib combined with trastuzumab (18.18%), and pyrotinib monotherapy (8.33%), pyrotinib combined with endocrine therapy, radiotherapy or antiangiogenic drugs (3.79%). A total of 132 patients were included in PFS analysis. mPFS was 12.0 months (95%CI 8.1-18.8). mPFS for patients without primary trastuzumab-resistant breast cancer was 14.1 months (95%CI 8.7-23.3). Patients receiving pyrotinib-based therapy as their ≥3 lines treatment had lower mPFS than those receiving pyrotinib-based therapy as their < 3 lines treatment (8.8 vs. 15.1 months, P= 0.119). mPFS in patients receiving regimen with and without capecitabine were 15.1 months and 8.4 months, respectively ( P= 0.081). As of data cutoff, mOS has not yet been reached. Among the 65 patients available for efficacy evaluation, 1 (1.54%) patient achieved complete response (CR), 24 (36.92%) patients had partial response (PR), 30 (46.15%) patients achieved stable disease (SD), and 10 (15.38%) patients had progression disease (PD), resulting in an ORR of 38.46% and DCR of 84.62%. The most common AE was diarrhea (84.17%), but only 5 (4.17%) patients were reported grade ≥ 3 diarrhea which could be well controlled. Other AEs with an incidence higher than 20.00% were anemia (36.67%), leukopenia (25.83%), vomiting (25.00%), neutropenia (22.50%). No treatment-related death occurred. Conclusions: Pyrotinib demonstrated an encouraging efficacy and manageable safety in patients with advanced HER2+ breast cancer. More data would be analyzed and reported in the future. Clinical trial information: ChiCTR1900021819.
Real-world Indian scenario of CDK4/6 inhibitors (palbociclib and ribociclib) with endocrine therapy in upfront hormone positive metastatic breast cancer.
Authors: Gogia Ajay , Arora Shalabh , Choudhary Priyanshu , Kumar Rakesh , Thulkar Sanjay , Deo S. V. S. , Sharma Dayanand , Bhatnagar Sushma 
Published: June 2021

e13028 Background: CDK4/6 inhibitors (CDKi), in combination with endocrine therapy (ET), has become the standard of care in the treatment of hormone positive (HR+)/ HER2 neu negative metastatic breast cancer (MBC) patients. We evaluated clinical outcomes and toxicity in MBC patients, who have received ET with two CDKi, namely palbociclib and ribociclib. Methods: This is an ambispective, single institutional analysis of de-novo HR+ MBC patients treated with CDKi (palbociclib 125 mg and ribociclib 600 mg once a day for 21 days /28 days cycle) from November 2016- October 2020 at AIIMS, New Delhi, India. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was response rate and toxicity. A total of 157 female patients were recruited in this study however the response and toxicity data were available in 120 cases. All premenopausal women received ovarian suppression or ovarian ablation. Results: A total of 120 patients were included in this study with a median age of 57 years (35-75) and 93 (77.5%) cases were postmenopausal. Twenty-three (19.1%) patients had a bone-only disease, 49 (40.9%) had bone and visceral disease and 48 (40%) had only visceral disease. In this study 91 (75.9%) patients received palbociclib and 29 (24.2%) received ribociclib. The median PFS was 18 months (4-36). Twenty four (20%) patients achieved a complete response, 69 (57.5%) patients attained partial response, 18(15%) patients had stable disease and 9 (7.5%) had disease progression. Grade 3–4 neutropenia, thrombocytopenia, and anaemia were observed in 18(15%), 8 (6.7%), and 4 (3.3%) cases respectively. None of the patients developed febrile neutropenia. Cutaneous, renal, hepatic, and gastrointestinal toxicity was observed in 1,1,3,4 cases respectively. Prolonged QTc was observed in one case. Grade 3 fatigue was observed in 7 cases. Dose interruption/delay (mean dose delay of 7 days), dose modification, and drug discontinuation were observed in 24 (20%), 12 (10%), and 10 (8.3%) of cases respectively. Conclusions: This is one of the largest real-world Indian data on CDK4/6 inhibitors on upfront HR+ MBC. Side effects are less than published literature with similar efficacy. Neutropenia was the most common side effect which was managed by brief dose interruption.
Neuroendocrine differentiation in metastatic breast cancer following CDK 4/6 inhibitors.
Authors: Sekkate Sakina , Ladrat Laure , Pouliquen Christelle , Callens Celine , Geay Jean Francois , Beuzeboc Philippe 
Published: June 2021

e13029 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered as a standard of care based on the compelling data across all landmark trials. Methods: We report our experience about two cases with metastatic breast cancer treated by CDK4/6 inhibitor in combination with an aromatase inhibitor, which develop neuroendocrine differentiation. After observing an unusual massive progression, a biopsy of the metastasis was performed in both patients. Both histological analysis confirmed a lobular breast cancer with small cell neuroendocrine features and a high proliferation index (KI 67 90%). An NGS (Next generation sequencing) profile was realized on primary and metastatic tumors to detect new acquired genomic alterations. Results: The comparative analysis of the NGS results of primary and metastatic tumors revealed the occurrence of several events in both patients under treatment. For one patient, we identified new mutations in the genes CDH1, FANCG, PIK3CA, PTEN and TP53, which did not exist initially. For the second patient, we found an amplification of the segment containing FGFR1, CCND1, FGF4, FGF3, FADD genes and the deletion of the segment containing RB1 andTP53 genes. Such events were not observed on the primary tumor. Conclusions: Prostate adenocarcinoma may develop neuroendocrine features in later stages of castration-resistant prostate cancer but neuroendocrine differentiation is atypical in breast carcinoma. In case of unusual rapidly progressive disease after CDK4/6 inhibitor, biopsy of new metastases should be recommanded to search neuroendocrine differentiation, or druggable mutations to guide the treatment.
Real-world analysis of disease progression after CDK 4/6 inhibitor (CDKi) therapy in patients with hormone receptor positive (HR+)/HER2- metastatic breast cancer (MBC).
Authors: West Malinda , Kaempf Andy , Goodyear Shaun , Kartika Thomas , Ribkoff Jessica , Mitri Zahi Ibrahim 
Published: June 2021

e13030 Background: CDKi with endocrine therapy (ET) is approved treatment of metastatic HR+/HER2- breast cancer based on PFS benefit vs ET alone. Outcomes data following CDKi discontinuation (dc) is limited, with trials ongoing in this setting. The reported phenomenon of rapid progression within 4 months of CDKi dc raises concern over CDKi impact on HR+/HER2- MBC biology. This study aims to define outcomes after CDKi dc and identify predictors of progression. Methods: This is a retrospective review of women ≥18 years with HR+/HER2- MBC who received CDKi between 4/1/14 and 12/1/19. Patient and tumor characteristics, pre and post CDKi tx, and reason for CDKi dc were collected. Time to event outcomes from date of CDKi dc (primary = PFS, secondary = Overall Survival, OS) were analyzed with Kaplan Meier estimators and Cox regression. Results: Analysis included 140 patients (median age 65 years), with most MBC (84%) arising from earlier stage disease. 51% of MBCs had visceral disease, and 66% received tx prior to CDKi. The most common CDKi was palbociclib (93%); and most common ET were letrozole (52%) and fulvestrant (40%). Median CDKi tx duration was 9 months (3.5 – 17.4) with 80% dc due to progression. Post CDKi txs included chemotherapy (44%), ET (24%), targeted tx (21%), no further tx (7%) and CDKi tx (4%). Median follow up was 12 months. mPFS post CDKi dc were 6.5 months (95% CI: 5.0 – 7.9) and 11.3 months (95% CI: 4.6 – 23.7) in patients who dc CDKi due to progression or other reasons, respectively (HR 1.77, 95%CI: 1.10-2.85). Among 112 patients who progressed on CDKi, estimated 4-month incidence of post CDKi progression or death was 31% (Table ). mOS post CDKi dc was 15.4 months (95%CI: 13.3-19.0) and mOS post CDKi initiation was 26.5 months (95% CI: 23.3 – 34.3). Visceral disease (HR 1.45, 95%CI: 1.01-2.08) and progression as reason for CDKi dc (HR 1.77, 95%CI: 1.1-2.85) were predictors of PFS (p < 0.05). Receiving fulvestrant with CDKi (HR 1.42, 95%CI: 0.96-1.0), prior chemotherapy in the metastatic setting (HR = 1.39, 95% CI: 0.90 – 2.14), and shorter CDKi duration were associated with non-significant increased risk of PFS. Conclusions: Rapid progression or death at 4 months occurred in 31% of MBCs following CDKi dc due to progression. Ongoing studies to define clinical and molecular characteristics of rapidly progressing tumors are underway to develop targeted tx approaches and improve outcomes.[Table: see text]
Real-world outcomes from the systemic use of CDK 4/6 inhibitors (CDKIs) in the management of ER positive (+) HER2 negative (-) metastatic breast cancer (mBC).
Authors: DeSouza Karen , Yeo Daniel , Diossy Maria , Umar Sumbal , Gore Emma , Trivedi Sachin , Anand Anjana , Madhusudan Srinivasan , Khan Sarah 
Published: June 2021

e13031 Background: The use of CDKIs have transformed the management of ER+HER2- mBC. As the real-world data matures, this project describes patterns in response to systemic therapy that may inform treatment planning and prognostication. Methods: We analysed the ER+HER2- mBC dataset at Nottingham University Hospitals NHS Trust (NUH) generated by reviewing clinical notes, radiology and e-prescribing records to collect clinical data on patients treated with CDKIs between 01/10/2016 - 01/10/2020. Results: 272 patients with a median age of 65 years (30-90 years) were treated with CDKIs (palbociclib 54.0% (n=147); ribociclib 19.5% (n=53); abemaciclib 26.5% (n=72)) in combination with endocrine therapies (letrozole, anastrozole, exemestane and, fulvestrant). Median overall survival was 49.5 months. Treatment with first-line CDKIs (69.8%; n=190) resulted in superior PFS when compared to CDKIs in a ≥ second-line setting (30.2%; n=82) i.e., mPFS 21.3 vs 12.2 months (HR 0.67; 95% CI, 0.47-0.96; P=0.02). Univariate analysis shown in the table below indicates the benefit to PFS from presentations with de novo mBC and the absence of visceral metastases. In patients treated curatively for early breast cancer (EBC), better outcomes were demonstrated in patients presenting with mBC, >12 months versus ≤12 months of completion of adjuvant endocrine therapy i.e., mPFS 28.4 vs 12.1 months (HR 0.50; 95% CI, 0.30-0.84; P=0.004) when treated with first-line CDKIs. A multivariate analysis identified benefit to PFS from first-line therapy with CDKIs (HR 0.70; 95% CI, 0.49-1.01; P=0.05) and presentation with de novo mBC (HR 0.56; 95% CI, 0.37-0.85; P=0.006). The presence of visceral metastases was associated with poorer outcomes (HR 1.52; 95% CI, 1.08-2.15; P=0.01). Conclusions: This analysis confirms the PFS benefit from CDKIs demonstrated in clinical trials is mirrored in the real-world setting. The analysis was not powered to delineate survival benefit between the individual CDKIs. Presentations with mBC following a prior history of EBC, within ≤12 months of completion of adjuvant endocrine therapy, and with visceral metastases may help predict poorer clinical outcomes and may need to be considered when prognosticating and in treatment planning. This analysis is hypotheses-generating and we will confirm our findings in a prospective manner as the dataset is expanded.[Table: see text]