bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review and meta-analysis of post-progression outcomes in ER+/HER2- metastatic breast cancer after treatment with endocrine therapy and CDK 4/6 inhibitors within randomized clinical trials.
Authors: Munzone Elisabetta , Pagan Eleonora , Bagnardi Vincenzo , Montagna Emilia , Cancello Giuseppe , Dellapasqua Silvia , Iorfida Monica , Mazza Manuelita , Colleoni Marco 
Published: June 2021

1059 Background: CDK4/6 inhibitors combined with endocrine therapy (ET) deeply transformed the treatment landscape of HR+/HER2− advanced breast cancer. After progression with the combination, there are no established guidelines for an optimal sequencing of the various therapeutic options. Data from randomized clinical trials (RCT) suggest that subsequent progression free survival (PFS2) was not compromised by the use of these drugs and time to subsequent chemotherapy (TTC) may be delayed. Therefore, we performed a meta-analysis to evaluate the benefit of such treatments on PFS2 and on delaying the TTC. Methods: We conducted a systematic literature search using PubMed to select all available randomized clinical trials of CDK4/6-inhibitors and ET reporting PFS2 or TTC data in first- or second-line therapy of HR+/HER2- pre- or postmenopausal metastatic breast cancer. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled hazard ratios (HR) for PFS2 and TTC with 95% confidence intervals (CI) using fixed-effects models. The pooled HRs for PFS and OS were also calculated. I2 was used to quantify heterogeneity between studies’ results. Results: Seven studies (PALOMA 1-2-3, MONALEESA 3-7, MONARCH 2-3) were included in our analyses (n = 3912 patients). A clear PFS2 benefit was observed in patients who received CDK 4/6 inhibitors + ET (pooled HR = 0.67, 95% CI = 0.61 to 0.74, I2 = 0.0%) and also a delay in subsequent TTC (pooled HR = 0.63, 95% CI = 0.58 to 0.70, I2 = 0.0%). As previously reported, the benefit in terms of PFS (pooled HR = 0.54, 95% CI = 0.50 to 0.59, I2= 0%) and OS (pooled HR = 0.77, 95% CI = 0.68 to 0.86, I2= 0%) was also confirmed. Conclusions: CDK4/6-inhibitors plus ET compared with ET alone improve PFS2, and TTC. The delay of chemotherapy can spare the patients toxicities, potentially improving the quality of life. Thus, the observed benefit in PFS2 may postpone the onset of endocrine resistance and may offer an additional therapeutic advantage in this setting.
Circulating tumor DNA (ctDNA) as a tool to help guide germline testing in patients with solid malignancies.
Authors: Patel Nikita Pankaj , Shah Ami N. , Davis Andrew A. , Gerattana Lorenzo , Jacob Saya , Katam Neelima , Wehbe Firas Hazem , Behdad Amir , Sciaraffa Theresa , Cristofanilli Massimo 
Published: June 2021

10602 Background: As the use of circulating tumor DNA (ctDNA) is more widely implemented, incidental identification of pathogenic variants reflecting germline alterations in cancer predisposition genes will occur more frequently. Such mutations are expected to have a high mutant allele frequency (MAF) or occur in genes typically associated with inherited syndromes. When a similar analysis was conducted by our group, we found that MAF of about 30% or greater in BRCA1/ 2 was associated with confirmed putative germline mutations in patients with breast cancer (Jacob et al & Davis et al, SABCS 2020). In this study, we extended this analysis to non-breast malignancies. Methods: Patients with non-breast solid malignancies and ctDNA testing between 2015-2020 were retrospectively identified from Northwestern Medicine. All ctDNA was analyzed using Guardant 360 (Guardant Health, Inc. Redwood City, Ca). Patients with ctDNA samples with mutations at high MAF (>30%) and those with BRCA1/2 mutations at any MAF were identified. We reviewed these charts for referral to genetic counselors and/or CLIA-approved germline testing. Descriptive analysis was reported for these findings. Genetic alterations were classified as pathogenic or of unknown significance based on OncoKB (Chakravarty et al, JCO PO 2017). Results: We identified ctDNA samples of 548 patients with non-breast solid malignancies, of whom 56 had gene mutations occurring at high MAF (>30%). Predominant cancer subtypes were lung (48%), colorectal (21%), pancreatic (7%), ovarian (3.5%), prostate (3.5%), and gastroesophageal (3.5%). The most common gene mutations identified were TP53 (46%), BRCA1/2 (18%), EGFR (18%), APC (13%), and KRAS (9%). 87.5% were pathogenic and 12.5% were of unknown significance. 11 patients (19.6%) had germline testing of whom 6 tested positive. These germline mutations were in BRCA2 (n = 3), EGFR, APC, and TP53. In addition to the 10 patients with BRCA1/2 mutations at high MAF (>30%), we identified 70 patients with BRCA1/2 mutations at low MAF ( < 30%). 54% were pathogenic and 46% were of unknown significance. 11 patients (14%) had germline testing of whom 3 tested positive for BRCA2, all at high MAF. 1 patient with a BRCA2 mutation at low MAF of 1.4% tested positive for a different germline BRCA2 variant. Conclusions: In patients with advanced cancers, ctDNA analysis can reveal variants with MAF >30% that are reflective of a germline mutation. Unfortunately the rate of genetic testing in these patients was low (20%). Future studies with germline testing in patients with high MAF variants would help understand the prevalence of germline variants. This can facilitate developing a more standardized approach for genetic counselor referral to identify families that may benefit from interventions for early detection or prevention of future cancers.
Endocrine therapy-based strategies with different endocrine sensitivity statuses for hormone receptor positive/HER2 negative metastatic breast cancer: A network meta-analysis.
Authors: Wang Jiani , Han Yiqun , Wang Jiayu , Xu Binghe 
Published: June 2021

1062 Background: Novel endocrine therapies (ETs) and targeted therapeutic regimens have been developed to dramatically improve the outcome of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Since the absence of direct head-to-head comparisons for all regimens, decision-making guidelines are urgently needed for different endocrine sensitivity statuses. This study is to evaluate the efficacy of ET-based regimens in patients with HR+/HER2- MBC and to assess the heterogeneity among different compounds with a particular focus on their ability to improve survival outcomes. Methods: This network meta-analysis of phase II/III randomized controlled trials (RCTs) with at least one ET in HR+/HER2- MBC were enrolled. Based on the endocrine responses, participants were stratified into endocrine therapy sensitivity (ETS) and endocrine therapy resistance (ETR) groups. Primary endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed by bayesian algorithms and primarily measured as surface under the cumulative ranking curve (SUCRA). Results: A total of 42 trials (22917 patients) were included. Regarding PFS, cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) +fulvestrant 500mg (F500) was recommended for the ETS group (SUCRA = 76.92%), while chemotherapy was considered as the most effective option for the ETR group (SUCRA = 73.47%). For visceral metastases, CDK4/6i +aromatase inhibitors (AIs) could provide the extreme efficacy for the ETS group (SUCRA = 63.27%) while the CDK4/6i +F500 (SUCRA = 76.17%) as the prior regimen for the ETR group. For bone-only disease, CDK4/6i+F500 was preferred for both the ETS (SUCRA = 67.04%) and the ETR (SUCRA = 70.24%) group. Concerning OS, CDK4/6i+tamoxifen was estimated as the first-rank regimen for the ETS subgroup (SUCRA = 67.04%) and chemotherapy for the ETR subgroup (SUCRA = 60.02%). Regarding resistance category, abemaciclib +F500 was likely the best option with PFS, for both primary (SUCRA = 69.19%) and secondary ETR (SUCRA = 69.09%) settings, as well as primary ETR associated with OS improvement (SUCRA = 67.67%). Pictilisib +F500 could be the optimal treatment with OS for secondary ETR (SUCRA = 60.50%)group. Conclusions: The results showed that CDK4/6i + F500 was probably the most promising option in ETS, visceral ETR and bone-only disease settings in terms of PFS. OS subgroup analysis showed that different endocrine sensitivity statuses required various optimal treatment strategies.
Efficacy of DAN-222, a novel investigational polymeric nanoparticle with topoisomerase I inhibitor, as monotherapy in breast cancer models and when combined with PARP inhibitor.
Authors: Wright Ashley P , Bradley Jodi D , Hagerty Timothy , Wyatt Emily A 
Published: June 2021

1081 Background: Patients with BRCA-positive HER2-negative breast cancer benefit from PARP inhibitor therapy, but additional benefit is still desired. PARP inhibition alone does not prevent all mechanisms for repairing damage to DNA such as homologous recombination repair. An attractive combination for treating such patients would be combining a topoisomerase I inhibitor with a PARP inhibitor given the dual mechanism this would provide for DNA damage and inhibited repair, leading to tumor cell death. This combination has been tried in multiple phase 1 studies, but myelotoxicity prevented the combination from being evaluated further. DAN-222 is a novel investigational polymeric nanoparticle conjugated with camptothecin, a topoisomerase I inhibitor, that provides significant accumulation of drug in tumor tissues via the enhanced permeability and retention (EPR) effect and significantly reduced bone marrow exposure compared to native chemotherapy. These observations underscore the potential advantages of DAN-222 alone as well as in combination with other agents such as PARP inhibitors in solid tumors. Here, we report the effects of DAN-222 monotherapy and in combination with a PARP inhibitor on the growth inhibition in an HRD+ TNBC breast cancer (MDA-MB-436) and an HRD- ovarian (OVCAR3) xenograft mouse model. Methods: HRD+ breast cancer tumor cells (MDA-MB-436) were implanted into female NCr nu/nu mice and HRD- ovarian cancer tumor cells (OVCAR3) were implanted into female CB.17 SCID mice. Mice were randomized to vehicle or treatment arms until tumors reached 2000 mm3 or day 45 (MDA-MB-436) or 1000mm3 or day 45 (OVCAR3). The groups evaluated include multiple dose levels of DAN-222 as monotherapy and those also combined with niraparib. Results: Results were consistent in both the HRD+ and HRD- tumor models with profound dose-response of DAN-222 monotherapy inhibiting tumor growth. Additionally, synergy was demonstrated when DAN-222 was combined with niraparib, clearly evident with low doses of both products when used in combination. The table below highlights the synergy of the combination of DAN-222 at 0.3 mg/kg and niraparib at 25 mg/kg above each agent alone on the tumor growth inhibition in the MDA-MB-436 xenograft. Conclusions: Combining a PARP inhibitor with a topoisomerase I inhibitor delivered via this polymeric nanoparticle delivery system (DAN-222) has synergistic efficacy in both HRD+ and HRD- xenograft tumor models. These data support continued development of DAN-222 to treat solid tumors and its combination use with PARP inhibitors.[Table: see text]
Distant metastases after diagnosis: Racial disparities in breast cancer outcomes.
Authors: Blanter Julia , Ramer Ilana , Ray Justina , Gallagher Emily J. , Bickell Nina A. , Tiersten Amy 
Published: June 2021

1084 Background: Black women diagnosed with breast cancer are more likely to have a poor prognosis, regardless of breast cancer subtype. Despite having a lower incidence rate of breast cancer when compared to white women, black women have the highest breast cancer death rate of all racial and ethnic groups, a characteristic often attributed to late stage at diagnosis. Distant metastases are considered the leading cause of death from breast cancer. We performed a follow up study of women with breast cancer in the Mount Sinai Health System (MSHS) to determine differences in distant metastases rates among black versus white women. Methods: Women were initially recruited as part of an NIH funded cross-sectional study from 2013-2020 to examine the link between insulin resistance (IR) and breast cancer prognosis. Women self-identified as black or white race. Data was collected via retrospective analysis of electronic medical records (EMR) between September 2020-January 2021. Distant metastases at diagnosis was defined as evidence of metastases in a secondary organ (not lymph node). Stage at diagnosis was recorded for all patients. Distant metastases after diagnosis was defined as evidence of metastases at any time after initiation of treatment. Univariate analysis was performed using Fisher’s exact test, multivariate analysis was performed by binary logistic regression, and results expressed as odds ratio (OR) and 95% confidence interval (CI). A p value <0.05 was considered statistically significant. Results: We identified 441 women enrolled in the IR study within the MSHS (340 white women, 101 black women). Median follow up time for all women was 2.95 years (median = 3.12 years for white and 2.51 years for black women (p=0.017)). Among these patients, 11 developed distant metastases after diagnosis: 4 (1.2%) white and 7 (6.9%) black (p=0.004). Multivariate analysis adjusting for age, race and stage at diagnosis revealed that black women were more likely to have distant metastasis (OR 5.8, CI 1.3-25.2), as were younger women (OR for age (years) 0.9, CI 0.9-1.0), and those with more advanced stage at diagnosis. Conclusions: Black women demonstrated a far higher percentage of distant metastases after diagnosis even when accounting for age and stage. These findings suggest that racial disparities still exist in the development of distant metastases, independent from a late-stage diagnosis. The source of existing disparities needs to be further understood and may be found in surveillance, treatment differences, or follow up.
U.S. radiation oncology and medical oncology department faculty diversity trends by sex and underrepresented in medicine status over five decades.
Authors: Kamran Sophia C. , Niemierko Andrzej , Vapiwala Neha 
Published: June 2021

11010 Background: Academic faculty are critical in training future generations of oncologists to care for our increasingly diverse cancer patient population. It is unclear if the growing imperative to address disparities in racial/ethnic and gender representation in the medical field has resulted in corresponding progress in the composition of academic radiation and medical oncology (RO, MO) departments. Herein we report trends in faculty diversity, overall and by academic rank, among US radiation and medical oncologists over the past 5 decades. Methods: Data were acquired from the Association of American Medical Colleges (AAMC) Faculty Roster between 1970-2019 for academic RO and MO departments to determine sex and race/ethnicity trends over five decades. Underrepresented in Medicine (URM) was defined as individuals identifying as Black, Hispanic, and Native American. Linear regression models were used to estimate slopes and associated p-values. Results: Total faculty complements grew over time in both RO and MO departments. The number of URM female faculty increased by 0.85/year in RO and 0.79/year in MO (P-trend<0.001), compared to non-URM female faculty, which increased by 11.3/year in RO and 7.9 in MO (P-trend<0.001). URM male faculty increased by 1.4/year in RO and 1.1/year in MO (P-trend<0.001), compared to non-URM male faculty, which increased by 25.5/year for RO and 12.2/year for MO (P-trend<0.001). Males represented the majority of URM and non-URM faculty for both RO and MO. The proportion of females grew more than the proportion of URM faculty over the study period for both RO and MO. There were also significant differences in diversity by faculty rank. Although MO outperformed RO in terms of the proportion of female faculty members with more advanced rank, female faculty members had a lower academic rank than their male counterparts in both specialties. At every rank, there was a low number of URM faculty represented among both MO and RO (Table). Conclusions: Gender and racial/ethnic diversity of academic RO and MO faculty has increased over time but has not kept pace with the diversity of the US population served, particularly with respect to URM status. The proportion of female faculty in both specialties demonstrates more promising growth, and may inform measures to achieve similar progress in recruiting and retaining URM faculty in both MO and RO.[Table: see text]
Impact of COVID-19 on work-related fatigue and satisfaction among oncology providers in Latin America: An analysis of the HOLA COVID-19 study.
Authors: Velazquez Manana Ana I. , Bernabe Ramirez Carolina , Olazagasti Coral , Bergerot Paulo Gustavo , Soto Perez De Celis Enrique , Corona-Cruz Jose Francisco , Riano Ivy , Adaniel Christina , Ramirez Francisca , Anampa Mesias Jesus Del Santo , Cajina Carmen , Mena Evelin , Gracia Elias , Menendez Alvaro G. , Bezares Raimundo , Castillo Fernandez Omar Orlando , Duque Duran Liseth , Corrales Luis-Alberto , Bergerot Cristiane Decat , Duma Narjust 
Published: June 2021

11014 Background: The well-being of oncology providers (OP) is in jeopardy with increasing workload, limited resources, and personal challenges that result from the COVID-19 pandemic. We aim to evaluate the impact of COVID-19 on work-related (WR) satisfaction and fatigue among OP in Latin America. Methods: We conducted an international cross-sectional online survey of OP practicing in Latin America. The survey was administered in English, Spanish, and Portuguese. Data was analyzed using descriptive statistics and Chi-square tests. Results: In August 2020, 704 OP from 20 Latin American countries completed the survey (77% of 913 who started the survey). Table outlines baseline characteristics. Higher frequency of WR fatigue (67% vs. 58%, p=0.010) and exhaustion (81% vs. 70%, p=0.001) were reported by OP who cared for patients with COVID-19, compared to OP who cared for patients without COVID-19. Providers that observed delays in referrals to radiation (p=0.002) and surgery (p=0.04) reported WR fatigue at higher rates than their counterparts. Higher exhaustion (p=0.016) and dissatisfaction (p=0.046) were reported by OP who lacked access to supportive services, as social work. A significantly higher proportion of women reported WR fatigue (72% vs. 56%, p=0.003) and exhaustion (86% vs. 68%, p=0.001), when compared to men. Women were more likely than men to endorse higher current levels of fatigue when compared to pre-COVID-19 (61% vs. 46%, p=0.0001). To reduce stress, women were more likely than men to cut the time spent watching the news (p=0.002). Both genders declined research collaborations and speaking opportunities. Conclusions: Fatigue and dissatisfaction with work-life were prevalent among OP in Latin America. Higher rates of WR fatigue were seen in women, OP caring for patients with COVID-19, and OP with patients who experienced cancer care delays. Our data imply that OP may be a prime target for psychosocial support, particularly as current challenges will continue for the foreseen future. Baseline characteristics (N=704).[Table: see text]
How to teach Breast ERAS protocols: Surgical residents’ perspectives and perioperative practices for mastectomy patients.
Authors: Jogerst Kristen , Coe Taylor , Gupta Nikita , Cronin Patricia , Fingeret Abbey , Pockaj Barbara A. 
Published: June 2021

11033 Background: Breast enhanced recovery after surgery (ERAS) protocols emphasize multimodal analgesia to decrease pain and expedite home recovery, but variability remains for same-day discharge and pain management. The purpose of this qualitative study is to examine how residents learn and apply breast surgery ERAS protocols, how they conceptualize pain management for breast surgery patients, and what influences their decision to discharge a patient home on the day of surgery. Methods: A semi-structured interview guide was adapted from existing instruments in the pain management qualitative literature. Surgical residents who rotated on the breast surgery service within the previous 12 months were interviewed by a single researcher. Interviews were recorded, transcribed, de-identified, and independently inductively coded by two researchers. A codebook was developed and refined using the constant comparative method until interrater reliability (Cohen’s kappa) reached greater than 0.9. Codes were grouped into coding categories and explored for thematic analysis. Results: Twelve interviews were completed with plastic and general surgery residents. Participants spanned post-graduate years 1-4. Preferred discharge narcotic regimens for mastectomy patients ranged from 5-30 tablets of 5mg oxycodone and participants rarely reported the same quantity. Ultimately, 365 primary codes were collapsed into 26 parent codes, with a Cohen’s kappa of 0.93. Six emerging themes were identified. Three themes describe how participants learned through a mixture of templated care, formal education, and informal experiential learning. Two themes delineate how residents would teach breast surgery ERAS protocols: by emphasizing buy-in and by connecting the impetus behind ERAS with the implementation in daily workflow. One theme illustrates the patient-centered culture and how that impacts postoperative management and same-day discharges. Conclusions: Residents learn breast surgery ERAS and postoperative pain management from imitating their seniors, observing patient encounters, completing templated orders, and translating concepts from other ERAS services, more so than from a formal lecture. When implementing new same-day discharge protocols for mastectomy patients, it is important to consider how informal learning and local culture influence postoperative pain management and discharge rates.