bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment pattern of early-stage premenopausal breast cancer patients with low Oncotype DX score: Single center experience.
Authors: Al Saheli Zaid Ihab , Ammari Omar , Albusoul Linda , Dabak Vrushali S. 
Published: June 2023

e12510 Background: The predictive value of Oncotype DX in early-stage node negative breast cancer had been previously well established. As per TAILORx, patients with a low Oncotype DX Recurrence Score RS (0–25) did not benefit from chemotherapy. Premenopausal patients are a crucial subgroup for which recommendations based on Oncotype DX are imprecise. Those with Oncotype DX RS 16-25 are thought to have a small benefit from chemotherapy. Our goal was to study the treatment pattern for this group of patients managed at our institution. Methods: We conducted a retrospective analysis to assess premenopausal patients with early-stage breast cancer who had Oncotype DX testing done. All eligible patients were compared based on whether chemotherapy was given or not. The primary endpoint evaluated was the rate of local recurrence. Univariate comparisons were assessed using t-tests or ANOVA for continuous variable & chi-square for categorical variable. Results: A total of 506 patients younger than 50 years diagnosed between 01/2018 and 12/2020 who had an Oncotype DX available were identified. Of these, 344 were White, 137 were Black and 23 identified as another race. The average age of patients was 42.7 ± 5.5 years. Patients treated with chemotherapy were found to be on average younger than those who did not receive chemotherapy (42 years old vs 43.6 years old, P < 0.0001). The average tumor size for patients who got chemotherapy was 3.26 cm compared to an average size of 2.78 cm for patients who avoided chemotherapy. 72.1% of patients with stage 2 disease had received chemotherapy compared to 38.1 % of patient with stage 1. There were 462 patients with RS < 16, 28 patients with RS 16-25, and 16 patients with RS > 25 as illustrated. Patients were followed from a range of 1.8 months to 30.7 months. There were 6 patients who had local recurrences identified, all of which had RS scores < 16. Conclusions: In our study, 91.3% had RS < 16 and generally should have avoided chemotherapy, however 35% of these patients continued to receive chemotherapy. Only 5.5% of our population had RS 16-25, a quarter of which (n = 7) received chemotherapy. Of those 7 patients, 3 had positive lymph node disease. None of these patients had disease recurrence to date. Patients with RS >25 made up 3.2% of the population and would generally benefit from chemotherapy, however 12.5% of these patients did not end up receiving it. Using Oncotype DX in early-stage breast cancer helps avoid chemotherapy safely in majority of patients. [Table: see text]
The safety of breast reconstruction: The impact of breast reconstruction surgery on postoperative adjuvant therapy for breast cancer.
Authors: Nagura Naomi , Ogiya Akiko , Nogi Hiroko , Narui Kazutaka , Mori Hiroki , Sasada Shinsuke , Ishitobi Makoto , Kondo Naoto , Yamauchi Chikako , Koike-Shimo Ayaka , Saiga Miho , Seki Hirohito , Sakurai Teruhisa , Shien Tadahiko 
Published: June 2023

e12511 Background: Postoperative adjuvant therapy is very important in treating breast cancer, and increasing numbers of patients are undergoing immediate breast reconstruction (IBR) at the same time as breast cancer surgery. However, the impact of breast reconstruction surgery on adjuvant therapy is controversial. In this multicenter cohort study led by the Japanese Breast Cancer Society, we examined the impact of reconstructive surgery on postoperative adjuvant therapy in breast cancer patients who underwent IBR. Methods: We examined the association between adjuvant therapy and complications of reconstructive surgery in 4726 patients with primary breast cancer who underwent IBR during the period from January 1, 2008 to December 31, 2016. Statistical analysis employed the χ2 test. Results: Of the 1044 patients who received adjuvant chemotherapy, the median time from the date of surgery to the start of chemotherapy was 51.0 days, with 65 patients (6.2%) starting more than 90 days after surgery. 66 IBR complications required surgery, including infections and tissue expander (TE) removal. Of the 65 patients for whom chemotherapy was initiated 90 days or more after surgery, 9 patients (13.8%) had complications requiring surgery, significantly more than the 57 patients (5.8%) in the < 90 days group (P = 0.010). Post-mastectomy radiation therapy (PMRT) was performed after breast cancer surgery in 359 cases: 69 cases received autologous tissue irradiation, 46 TE irradiation, 241 silicone breast implant (SBI) irradiation, and 3 removal before irradiation. 5 cases given autologous tissue irradiation and 30 receiving artificial material irradiation required surgery within 1 year after the cancer surgery due to complications of IBR. There was no significant difference in the frequency of complications requiring surgery between autologous tissue irradiation and artificial material irradiation (P = 0.422). There were 35 complications (9.7%) requiring surgery in the irradiated group, significantly more than the 118 cases (2.7%) in the non-irradiated group (P < 0.001). Conclusions: Adjuvant chemotherapy was generally not delayed, but complications requiring surgery related to IBR were more frequent in those with delay beyond 90 days, suggesting that postoperative complications from breast reconstruction may have influenced the delay in initiating chemotherapy. Therefore, in cases for whom postoperative chemotherapy is anticipated, complications from breast reconstruction may have impacted outcomes, making preoperative risk assessment even more important. There was no difference in the frequency of reconstructive complication surgery according to whether autologous tissue irradiation or artificial material irradiation had been used, but further investigation is needed.
An analysis of National Cancer Data Base: Male breast cancer and overall survival.
Authors: Albagoush Sara , Masih Durva , Wu Xinxin , Swedek Michelle , Randhawa Saboor Ejaz , Silberstein Peter T. 
Published: June 2023

e12513 Background: Male breast cancer unlike female breast cancer is rare, representing approximately 1% of cancers that occur in men and approximately 1% of all BCs worldwide. It is managed by extrapolating from breast cancer in women due to it is rarity. We aimed to perform a large retrospective study with a focus on disease characteristics and overall survival. Methods: We performed a retrospective analysis of male breast cancer patients from the National Cancer Database (2004–2020). We obtained demographic, tumor, clinical and therapy data. Kaplan-Meier survival curves were created to estimate overall survival. Cox regression analysis was used to compare the groups within each variable. Results: We identified 31348 patients with primary diagnosis of male breast cancer (median age 66 years). Patients were predominantly white (82.1%) then black (13.4%). Most of patients are located in urban or metropolitan areas (95.9%) within a median of only 8.4 miles from the hospital where they received care. Almost equal patients treated at community hospitals (48.2%) and academic hospitals (50%). Patients were mainly covered by Medicare (49.0%) then Private insurance (40.8%). Most men who diagnosed with MBC had invasive cancer (88.3%). Only 1433 (4.6%) patients presented with metastases at diagnosis. The median tumor size was 3 cm. Most of tumors were moderately differentiated (36.1%) then (24.0%) poorly differentiated. In most patients, the tumor is present in the central portion of the breast. Several treatment modalities were used, of which primary surgical resection was the most common [90.7%). Among systemic therapies, hormonal therapy was the most common (57.1%%) then chemotherapy (34.3%) then radiation therapy (30.6%) and immunotherapy (4.8%). In terms of duration, time from diagnosis to surgery was 26 days (shortest), diagnosis to immunotherapy was 57 days, diagnosis to chemotherapy was 59 days, and time from diagnosis to radiation was 145 days (longest). The overall 30-day mortality was 0.3% (75/26333), the 90-day mortality was 0.9% (224/26333). Median overall survival is 67.1% (95% CI 143.371-150.349). Using cox proportional hazards model; factors influencing survival rate including Age, race, CDS P < 0.001, tumor size, year of diagnosis P < 0.000. All treatment modalities including surgery, chemotherapy and hormonal therapy was associated with increase overall survival with P < 0.001 (95% CI 1.245-1.370). Conclusions: This is the largest study to date on epidemiology and prognostic factors for MBC using NCDB. Old age, white race, greater comorbidity index, and larger tumor size are associated with decreased survival. Surgery and adjuvant therapy are associated with increased overall survival. Further studies warranted to elucidate the causes of improved survival associated with some of these factors will help improve quality of care for patients with MBC.
Exosome-based delivery of microRNAs to confer adriamycin-resistance to sensitive cells through modulating the immune- and metabolism-related gene PTEN in HER2-negative breast cancer.
Authors: Yang Sujin , Tang Jinhai 
Published: June 2023

e12518 Background: Anthracycline-based chemotherapy is frequently used to treat breast cancer. However, acquired drug-resistance remains a challenge for successful treatment. Recent evidence suggests that in addition to increased tumor cell resistance, modifications in the tumor immune microenvironment (TIME) consistently contribute to the development of chemo-resistance. Methods: TIME scores and tumor-infiltrating immune cells (TICs) scores were used to investigate clinicopathological characteristics and gene transcriptome profiling of 142 HER2-negative breast cancer patients who received anthracycline-based chemotherapy. Exosomes isolated from MCF/7-ADR (ADR-exos) and MCF/7-S (S-exos) cell lines were characterized. MiRNA microarray and TMT mass spectrometry analysis were used to identify differentially expressed miRNA and its target genes. The ability of ADR-exos to transfer drug-resistance mediated by miR-222 was assessed by immunofluorescence assay, flow cytometry and qRT-PCR. We optimized the conditions to load miR-222 mimic (or inhibitor) into exosomes produced by HBL-100 cells (H-exos). The influence of miR-222 inhibitor-containing exosomes on the downstream pathway of miR-222 and the potential therapeutic effects both in vitro and in vivo were evaluated. Results: Firstly, we discovered the complicated and heterogenous TICs subtypes and their unique biological behaviors in HER2-negative breast cancer. Gene set variation analysis (GSVA) was used to quantify 85 differentially expressed immunologic signature gene sets and 7202 corresponding immune-related genes. Using miRNA microarray analysis and TMT mass spectrometry, 45 differentially expressed immune-related proteins affected by the miR-222 level were identified, particularly PTEN, a well-known tumor suppressor factor. Furthermore, we successfully established miRNA mimic/inhibitor-containing exosomes to explore the individual function of exosomal miR-222 in promoting adriamycin-resistance both in vitro and in vivo. Conclusions: HER2-negative breast cancer patients own unique TIME subtypes, leading to different outcomes of chemotherapy. We exhibit the potential applications of miR-222-mimic/inhibitor-containing exosomes for reversing chemo-resistance. Adriamycin-resistant cells can transmit drug-resistance to sensitive cells via delivering miR-222 by modulating the immune- and metabolism-related target gene PTEN both in vitro and in vivo without interference from other relevant drug-resistance factors in exosomes. Therefore, miR-222-containing exosomes as well as the target gene PTEN may be a promising biomarker to predict the chemo-resistance and tumor immunomodulatory effects of Anthracycline-based chemotherapy in HER2-negative breast cancer patients.
HR+/HER2- Breast cancer: The effect of online education on clinician knowledge, competence, and confidence in monitoring, mitigating toxicities, and developing patient-centric plans using a team-based approach.
Authors: Patel Urvi , Dorkhom Nabil , Phoenix Victoria , Cohen Jacob 
Published: June 2023

e12522 Background: CDK4/6 inhibitors provide effective treatment options for patients with HR-positive, HER2-negative breast cancer (BC), but adherence and persistence can be challenging. To address this gap, a global educational activity was developed that consisted of a 2-hour live streaming virtual meeting with interactive workshops and a 45-minute online enduring activity. The objective of this study was to assess the educational impact of the online enduring educational activity. Methods: To assess educational impact a repeated-pairs pre-/post-assessment study design using 3 knowledge/competence questions, in which everyone served as their own control. A paired samples t-test assessed mean differences in average number of correct responses pre- to post-assessment, and a McNemar’s test assessed significance of improvement in single questions from pre- to post-assessment. P values < .05 are statistically significant. Confidence was also assessed using a pre/post confidence question. The activity launched on June 4, 2021, and data was collected till March 30, 2022. Results: 80 oncologists from outside the US (OUS) and 69 oncologists from the US who answered all the assessment questions were included in the analysis. Each question assessed a learning objective. All three knowledge/competence learning objectives showed a significant improvement in the OUS oncologist group, and 2 of the 3 showed a significant improvement in the US group. Conclusions: This online enduring activity resulted in a significant improvement of oncologists’ knowledge and competence related to clinical evidence for the use of CDK4/6i, managing adverse events associated with CDK4/6i and monitoring patients on CDK4/6i. Confidence of oncologists in counselling patients on the importance of adherence to CDK 4/6 inhibitor therapy also improved in 29% of OUS oncologists and 33% of US oncologists. However, there is still a need for education in a significant percentage of both OUS and US oncologists on this topic. [Table: see text]
Longitudinal trends in serum calcium, parathormone and bone mineral density in breast cancer survivors on aromatase inhibitor therapy: A single institutional cohort study.
Authors: Sorathia Sharmeen , Ogbue Olisaemeka , Unlu Serhan , Nanah Abdel Rahman , Abdeljaleel Fatima , Alqaisi Sura , Serhal Dina , Haddad Abdo S. , Daw Hamed 
Published: June 2023

e12531 Background: Aromatase inhibitors (AIs), when used as adjuvant treatment of hormone receptor positive breast cancer, have been associated with bone density loss. However, any impact on PTH and by extension calcium (Ca) homeostasis is yet to be elucidated as no study till date has investigated longitudinal trends in parathyroid hormone (PTH) while on AI therapy. We explored these to determine if long term AI therapy was associated with hyperparathyroidism. Methods: This is a retrospective study of female breast cancer patients at the Cleveland Clinic Foundation started on AIs (anastrozole, letrozole and exemestane) from January 2015 to April 2022. Included patients had both baseline and subsequent data (after starting AI therapy), on serum Ca, PTH and lumbar spine T-scores (LsTs). These values were compared using paired t-test. Results: We identified n=9657 patients on AI therapy and included n=249 with pre and post AI PTH values. Among these, n= 209 received anastrozole, n=34 received letrozole and n=6 received exemestane. Cohort median age was 68 (IQR 62-72) years and median duration of AI therapy was 3 years. While we observed a significant positive correlation between change in Ca and change in PTH (p=0.02), the differences between baseline and treatment median serum Ca and PTH were not statistically significant. There was no significant association between changes in either serum Ca or PTH and change in LsTs (p-value: 0.69 and p-value: 0.05 respectively). Notably, 4% patients had elevated PTH and Ca after AI therapy was initiated among whom n=4 had markedly elevated PTH with low urinary Ca. Three of these four patients also had a diagnosis of chronic kidney disease (CKD) with normal vitamin D levels. Two patients with elevated PTH were on biotin supplements. There was an overall downtrend in LsTs (p-value: 0.0039) with no significant difference between the three AIs (p-value 0.0613). However, in comparison to other AIs, letrozole had the least depreciation in LsTs. Conclusions: Our findings do not suggest any correlation between AI therapy and hyperparathyroidism among breast cancer survivors. No significant increase in PTH levels occurred during AI therapy and majority of patients with clinically significant PTH elevation also had CKD, which may have contributed also to elevation of PTH level and low urinary calcium excretion.[Table: see text]
Lowering the bar for consideration of neoadjuvant chemotherapy in early-stage HER2-positive breast cancers.
Authors: Godbole Manasi Manoj , Meranda Matthew , Shango Kathren , Dabak Vrushali S. 
Published: June 2023

e12534 Background: The use of neoadjuvant chemotherapy (NAC) has contributed to increased rates of disease-free survival (DFS) as well as overall survival in breast cancer patients, specifically those with HER2-positive disease. Stage 2 patients with HER2-positive disease including tumors > 2cm as well as node positive disease receive neoadjuvant chemotherapy as per current NCCN guidelines. The aim of our study was to understand outcomes in patients with early breast cancer receiving chemotherapy. Methods: We extracted data on patients with initial clinical stages IA-IB breast cancer who had HER2-positive status on initial biopsy and received chemotherapy plus anti-HER2 therapy in the Henry Ford Health System between January 2016 to June 2020. Patients with T2 or above and/or node positive disease were excluded. Results: Of the 229 total patients that met eligibility criteria, 159 (71%) were white, 65 (28%) were African American. 99% were females. The median age at diagnosis was 61 years. Estrogen receptor positivity was noted in 85% (196/229) of the patients. NAC was given to 56 patients (24%) of which 26 (46%) were African American and 45 (80%) were hormone receptor positive. 5 (9%) patients achieved pathological complete remission (CR). Remaining 51 patients (91%) did not have pathological CR. Of these, 17 (33%) patients had the same stage at surgery after NAC and 34 (66%) were upstaged on final pathological evaluation. 21 patients with residual disease (41%) underwent treatment change in the form of either ado-trastuzumab emtasine (TDM-1) or additional radiation therapy or repeat surgery. Of note, 34 of the 51 patients were treated for residual disease after 2019 with TDM-1. 54 (95%) patients are alive currently. Of the 173 patients that received adjuvant chemotherapy (76%), 39 (23%) were African American and 150 (87%) had hormone receptor positive disease. 19 of these (11%) were upstaged at surgery compared to the initial biopsy requiring treatment change. 163 (94%) are alive currently with no disease recurrence. Conclusions: Our study results suggest that NAC is used in minority of breast cancer patients, especially with stages 1A and 1B. Pathological CR rate in our study population was low and majority of patients who got NAC as well as a small percent of those who received adjuvant chemotherapy had disease upstaged based on surgical pathology results. We believe that this could be because of inaccurate initial staging due to limitations of imaging techniques and our population being mostly hormone receptor positive. With approval of TDM-1 in patients with residual disease post NAC, we may be able to improve outcomes in terms of recurrences and survival in these patients. Thus, consideration of NAC for early stage HER2-positive breast cancers appears attractive and data like our study may support ongoing prospective clinical trials.
FcεRIγ-negative NK cells and association with improved outcomes in trastuzumab-treated patients.
Authors: Perez Vincent Michael , Selitsky Sara R. , Yao Bin , Bigley Austin , Kim Sungjin , Frohlich Mark Walter 
Published: June 2023

e12538 Background: A subset of natural killer cells lacking FcεRIγ expression (g-NK cells) demonstrate enhanced expansion, cytokine production, antibody-dependent cytotoxicity, and enhanced efficacy of therapeutic antibodies in preclinical models (Bigley, Blood Advances 2021). The monoclonal antibody, trastuzumab, is standard of care for treatment of HER2+ breast cancer in adjuvant and metastatic settings. We sought to determine whether the abundance of g-NK cells is associated with improved outcomes in trastuzumab-treated patients. Methods: We identified g-NK cells in single-cell (scRNA-seq) datasets from melanoma (n=47), renal (n=8), breast (n=29), and lung cancer (n=36) samples using predefined markers and defined a g-NK gene signature. We split the scRNA-seq cohorts into training and test sets and estimated cell-type compositions in pseudo bulk using MuSiC bulk tissue deconvolution (Wang, Nature Communications, 2019). We deconvoluted g-NK cells in 8 bulk RNA-seq HER2+ breast cancer cohorts (Table 1) and used Cox proportional hazard models to assess clinical outcomes stratified by g-NK and trastuzumab status. We reproduced our findings using real-world cohorts from patients sequenced via the Tempus xT test (Table 1). Results: The Spearman’s correlation coefficient between true and estimated pseudo bulk proportion of g-NK cells was 0.71 (p≤0.05). In a meta-analysis, the abundance of g-NK cells was associated with a lower hazard ratio (HR) for overall survival (OS) in trastuzumab-treated patients (cohorts 1-4; HR = 0.61; 95% CI, 0.37-0.99; p=0.04) but not trastuzumab-naive patients (cohorts 5-8; HR = 0.96; 95% CI, 0.80-1.15; p=0.65). In real-world, HER2+ breast cancer cohorts treated with trastuzumab, higher real-world progression-free survival (rwPFS) was associated with abundance of g-NK cells (N=104, HR = 0.78; 95% CI, 0.64-0.96; p=0.02). A similar trend was observed in real-world trastuzumab-treated gastric cancer patients (N=79, HR = 0.85; 95% CI, 0.72-1.00; p=0.06). Conclusions: G-NK cells are associated with improved OS and PFS in trastuzumab-treated patients from both clinical trials and real-world datasets, suggesting their presence may serve as a predictive marker for treatment efficacy. Adoptive transfer of g-NK cells is being explored to augment the efficacy of therapeutic monoclonal antibodies. [Table: see text]