bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant weekly carboplatin and paclitaxel followed by dose dense adriamycin/cyclophosphamide in locally advanced triple negative breast cancer: A single-center experience in a safety net hospital.
Authors: Chen Nan , Bulsara Shaun , Hilsenbeck Susan G. , Rimawi Mothaffar F. , Nangia Julie R. 
Published: June 2021

e12629 Background: Locally advanced triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer comprising 10-15% of new diagnoses each year. Optimization of neoadjuvant therapy is necessary to decrease risk of relapse. Carboplatin has been explored as an addition to standard chemotherapy to increase rates of pathologic complete response (pathCR) and improve disease free (DFS) and overall survival. Studies have shown varying degrees of benefit, and the ideal usage of carboplatin remains unclear. Methods: A retrospective chart review was conducted in the Harris County Health System to examine outcomes of patients receiving carboplatin. 71 patients with TNBC were identified as treated with weekly carboplatin at an AUC of 2 and paclitaxel followed by dose dense adriamycin/cyclophosphamide (ddAC) between 2015 and 2020. Results: The average age at diagnosis was 50 (range 31 – 73). 44 (62%) patients were Hispanic, 19 (27%) were African American. 11 (15%) were BRCA carriers. 30 (42%) patients had clinical Stage II disease, 41 (58%) patients had clinical stage III disease. 53 (75%) patients had T3 or T4 disease. 48 (68%) patients had nodal disease at diagnosis. The pathCR rate for the overall population was 43%, of the patients who did not achieve a pathCR, 6 (15%) had residual cancer burden (RCB) I, 21 (51%) had RCB II, and 14 (34%) had RCB III at the time of surgery. 5 year disease free survival (DFS) after surgery for all patients was 70% (95% CI 56-86%). 5 yr DFS was 63% (95% CI 45-88%) for patients without pathCR compared to 79% (95% CI 62-100%) for patients with pathCR (p = 0.3, logrank test). 61% of patients had between 3 – 5 adverse events. 30 (42%) patients required a treatment delay. 12 (17%) patients required treatment discontinuation. The most common serious adverse event was neutropenia affecting 9 (12%) patients. Conclusions: Our single center data in a safety net clinical setting demonstrates that a neoadjuvant regimen of weekly carboplatin/taxol followed by ddAC was safe and efficacious in a high-risk group of primarily minority patients. Despite having more advanced disease compared to patients in randomized trials receiving weekly carboplatin such as GeparSixto, our patients still had similar response rates. Additionally, our data supports the continued use of pathCR as a valid indicator of disease free and overall survival.
Evaluation of pathologic and genomic characteristics in female breast cancer patients.
Authors: Hansra Damien Mikael , Moran Amber , Slawik Becky , Clark Shirelle , Doctor Vicki , Parikh Ankur Rasik , Crilley Pamela A. , Lynch Cynthia , Nixon Daniel W. , Markman Maurie , Ahn Eugene R. 
Published: June 2021

e13001 Background: The genomic landscape of female breast cancer is rapidly evolving partially owing to advancements in next generation sequencing (NGS). Here we report the genomic characteristics of female breast cancer patients with locally recurrent inoperable and metastatic disease. Methods: IRB approval was obtained for a retrospective analysis of archived pathology on patients treated at Cancer Treatment Centers of America. Comprehensive genomic profiling of tumors was derived from Foundation One (F1) and Guardant 360 NGS. Clinical information was derived from retrospective chart review. Inclusions: adult females with breast cancer with stage IV metastatic disease or locally recurrent inoperable disease. Exclusions: Males, missing genomic and pathologic information. Results of clinical, pathologic, and genomic data were summarized. Results: 1788 patients met study criteria. Median age: 48 yrs., range 20-79 yrs. Race: Caucasian 1029/1788 (58%), African American 582/1788 (32%), Hispanic 77/1788 (4%), Asian 26/1788 (1%), other 73/1788 (4%). Receptor status: Hormone receptor ER(+) &/or PR(+) 950/1788 (53.1%); Triple negative 390/1788 (21.8%); HER2(+) 205/1788 (11.5%); missing/incomplete: 243/1788 (13.6%). Ki-67 status: High 548/705 (77.7%)/Low 57/705 (8.1%)/Intermediate (INT) 100/705 (14.2%). PD-L1 status: PD-L1(-) 346/544 (63.6%)/ PD-L1(+) 179/544 (32.9%)/PD-L1 (indeterminate or QNS) 19/544 (3.5%). NGS test total (1984 tests): F1 1023/1984 (52%), F1 CDx 703/1984 (35%), F1 Act 91/1984 (6%), F1 Liquid 82/1984 (6%), Guardant 360 85/1984 (4%). Biomarkers (1096 results): Microsatellite Instability (MSI) High 4/1096 (0.3%), MSI- Intermediate (INT) 2/1096 (0.1%), MS-stable 1017/1096 (93%), Cannot be determined (CBD) 73/1096 (7%). Tumor Mutation Burden (TMB) (842 results): TMB high 22/842 (3%), TMB INT 233/842 (28%), TMB low 513/842 (61%), CBD 74/842 (9%). Genomic abnormalities (% alterations per patient): TP53 999/1783 (56.03%), PIK3CA 610/1783 (34.21%), MYC 425/1783 (23.84%), CCND1 318/1783 (17.84%), FGF19 298/1783 (16.71%), FGF3 296/1783 (16.60%), FGF4 293/1783 (16.43%), ESR1 266/1783 (14.92%), FGFR1 276/1783 (15.48%), PTEN 239/1783 (13.40%), ZNF703 251/1783 (14.08%), ERBB2 218/1783 (12.23%), GATA3 178/1783 (9.98%), CDH1 165/1783 (9.25%), RAD21 157/1783 (8.81%). Pathway defects (expressed as total % of alterations): Alterations in FGF genes 10.64%, mTOR pathway 8.36%, HHR pathway 3.17%. Conclusions: Female breast cancer patients display a heterogeneous variety of complex genomic alterations. Mutations in FGF genes were most common. The single most common alteration was in TP53. Other common alterations include PIK3CA, MYC, CCND1, and ESR1.
Adherence to abemaciclib in patients receiving antidiarrheal medicine.
Authors: Shah Dipti , Byrd Brooke , Avalos-Reyes Elisea , McCarthy Amanda , Matlin Olga S. , Grover Rashmi , Feczko Lucia 
Published: June 2021

e13016 Background: According to the National Cancer Institute, breast cancer is the most common form of cancer in the United States. Nearly 75% of patients with breast cancer have tumors that are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative. In 2017, the U.S. Food and Drug Administration (FDA) approved abemaciclib to treat adult patients who have HR+ and HER2- advanced or metastatic breast cancer. While the adverse events associated with abemaciclib have been well documented in clinical trials, it is unknown if adverse events, specifically diarrhea, impact adherence. The purpose of this study is to determine whether adherence to abemaciclib differs for patients who receive loperamide in welcome kits versus those who do not receive loperamide in welcome kits. Methods: This is a retrospective study of patients throughout the United States with HR+, HER2- breast cancer who received abemaciclib from a large specialty pharmacy from July 1, 2018 to December 31, 2019. Patients who received welcome kits (each welcome kit contains three boxes, each box contains ten 2mg tablets of loperamide) served as the intervention group; patients who did not receive welcome kits served as the standard of care group. Baseline characteristics of patients in each group were compared with t-tests for continuous data and the chi square test for categorical data. Medication possession ratio (MPR), dose reduction and dose omission rates in the first three months of taking abemaciclib were compared. Results: We identified 1,180 breast cancer patients who received abemaciclib. The intervention group had 317 patients, with an average age of 60.1 y (SD = 12.0); the control group had 863 members, with an average age of 58.7 y (SD = 11.8). Baseline characteristics did not differ significantly between groups, except for geography (p<0.001), as seen in the table. There was no significant difference (p = 0.858) in mean MPR between the intervention and standard of care groups. There were no significant differences in dose reduction rates (p= 0.390) and dose omission rates (p = 0.872) within three months of starting abemaciclib. Conclusions: Our findings suggest that patients who receive loperamide in welcome kits do not have better adherence to abemaciclib therapy. In this study, both groups showed high adherence to therapy, suggesting that the standard of care group manages diarrhea just as effectively as the intervention group. A welcome kit with loperamide did not impact a patient’s adherence to abemaciclib therapy.[Table: see text]
Everolimus and exemestane in hormone receptor-positive advanced breast cancer: A comprehensive cancer center’s experience.
Authors: Moreira Inês , Ferreira Marta , Afonso Ana , Ferreira Ana , Rodrigues Ana , Vieira Claudia , Oliveira Cristina , Savva-Bordalo Joana , Dias João , Cassiano Maria , Abreu Miguel , Alves Sara , Sousa Susana 
Published: June 2021

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.
Relative bioavailability of H3B-6545 tablets versus capsules and drug-drug interaction between H3B-6545 and pantoprazole.
Authors: Xiao Jianjun Alan , Coleman Hugh A , Sahmoud Tarek , Gao Lei , Chong Weili , McAuley Sonja , Scholz Catherine , Gualberto Antonio 
Published: June 2021

e13022 Background: H3B-6545 is a selective, orally available, small molecule antagonist of the estrogen receptor (ER), covalently binding to a cysteine residue at position 530 of both wild-type and the constitutively active mutant ERα proteins. H3B-6545 demonstrated preliminary clinical antitumor activity in breasts cancer patients in phase 1b/2. Methods: This was an open-label phase 1 study to evaluate the relative bioavailability of H3B-6545 from a tablet formulation compared to capsules, and the effect of pantoprazole on the pharmacokinetics of H3B-6545, in healthy post-menopausal women. Subjects were randomized (1:1 ratio) to a combined crossover and fixed sequence 3 periods treatment: A single oral dose (SOD) of 450 mg H3B-6545 fasted on day 1 (capsules or tablets), followed by a 4-day washout; A SOD of 450 mg H3B-6545 fasted on day 5 (crossover formulation from the first period), followed by a 4-day washout; daily oral doses of 40 mg pantoprazole on days 9 to 15 with coadministration of a SOD of 450 mg H3B-6545 (tablets) on day 15. Results: A total of 16 subjects were enrolled and received at least one dose of H3B-6545 and 15 subjects completed all 3 periods. One subject assigned to the tablet/capsule treatment sequence withdrew from the study due to subject decision on day 13 (Period 3), following completion of Period 1 (H3B-6545 tablet) and Period 2 (H3B-6545 capsule). Following a SOD of H3B-6545 capsules alone, tablets alone, or tablets at steady-state QD of pantoprazole, H3B-6545 geometric mean Cmax was about 1070, 1120 and 1330 ng/mL, respectively, AUC was about 16600, 17500 and 18300 ng.h/mL, respectively, half-life was about 11.0, 11.0 and 10.2 hours, respectively, and the median Tmax was about 3.0, 4.0, and 2.0 hours post dose, respectively. The ratio (capsule/tablet) of Cmax and AUC was both about 0.95; steady-state pantoprazole QD increased H3B-6545 Cmax by 20% with no change in AUC. Nine subjects (56.3%) reported at least 1 TEAE during the study with constipation being the most common (43.8%); all TEAEs were mild in severity. There were no SAEs reported. Conclusions: Plasma PK of H3B-6545 is similar between tablets and capsules, and in the absence or presence of pantoprazole. Concurrent use of gastric acid reducers had a minimal effect on H3B-6545 exposure and was not considered clinically meaningful.
Everolimus combined with endocrine therapy in advanced HR-positive, HER2-negative Chinese breast cancer patients: A retrospective study.
Authors: Shen Xia-Bo , Li Guang-Liang , Zheng Ya-Bing , Chen Zhan-Hong , Cao Wen-Ming , Shao Xi-Ying , Wang Xiao-Jia 
Published: June 2021

e13023 Background: The Food and Drug Administration (FDA) approves the combination of everolimus and exemestane for the treatment of advanced breast cancer patients who are hormone-receptor (HR) positive but human epidermal growth factor receptor-2 (HER2) negative. However, there is little real-world data on the everolimus in Chinese breast cancer patients. Endocrine therapy is the main treatment for advanced HR-positive, HER2-negative breast cancer patients which includes aromatase inhibitor (AI) or fulvestrant. Drug resistance and subsequent treatment after endocrine therapy are some of the most clinical concerns. CDK4/6 inhibitors and HDAC inhibitors are poorly available due to high price, and combined everolimus therapy can be a non-ignorable choice for advanced HR-positive, HER2-negative breast cancer patients. Methods: We retrospectively collected the treatment information of advanced breast cancer patients treated with everolimus from 2013 to 2020 in Zhejiang Cancer Hospital. Kaplan–Meier analysis and Cox regression methods were used to calculate and compare the progression-free survival (PFS). Results: The study finally enrolled 84 patients meeting the requirement, and patients were postmenopausal or premenopausal while received ovarian function suppression. And 54 patients were in the everolimus+AI group, 30 patients were in the everolimus+fulvestrant group. The median PFS in all 84 patients was 6.87 months, and the median overall survival (OS) was 28.87 months. The DCR in all 84 patients was 76.2%, and the most common grade 3-4 adverse event is stomatitis which is similar to other previous studies. Subgroup analyses were further performed based on everolimus combined with AI/fulvestrant. Patients were well-balanced in clinical characteristics in the two groups. Everolimus combined with fulvestrant group showed no superior to everolimus combined with AI group, 5.77 vs. 7.97 months (HR, 1.56; 95% CI, 0.92-2.65, P = 0.0735). Subgroup analyses showed everolimus combined with AI groups was superior to Everolimus combined with fulvestrant groups in some subgroups: postmenopausal group (HR, 0.50; 95% CI, 0.26-0.98); without bone metastasis group (HR, 0.22; 95% CI, 0.06-0.80); lung or pleura metastasis group (HR, 0.35; 95% CI, 0.16-0.77); visceral disease group (HR, 0.37; 95% CI, 0.20-0.69); previous therapy lines ≥ 4 group (HR, 0.44; 95% CI, 0.22-0.87). Conclusions: Everolimus combined with fulvestrant is not superior to everolimus combined with AI in HR-positive, HER2-negative breast cancer patients. For postmenopausal patients, patients without bone metastasis, and patients with visceral disease, everolimus combined with AI is a better choice.
Phase 1b study of H3B-6545 in combination with palbociclib in women with metastatic estrogen receptor–positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
Authors: Johnston Stephen R. D. , Pluard Timothy J. , Wang Judy S. , Hamilton Erika P. , Juric Dejan , Scholz Catherine Rose , Hnitecki Elizabeth , Gao Lei , Cantagallo Lisa , Korpal Manav , Destenaves Benoit , Xiao Jianjun Alan , Zhang Zhaojie , Pipas J. Marc Marc , Yu Lihua , Sahmoud Tarek , Gualberto Antonio 
Published: June 2021

e13025 Background: H3B-6545, a highly Selective ERα Covalent Antagonist (SERCA), inactivates both wild-type and mutant ERα by targeting cysteine 530 and enforcing a unique antagonist conformation. At the dose of 450 mg daily, H3B-6545 has a manageable safety profile and demonstrated preliminary single-agent antitumor activity in heavily pretreated ER+, HER2- mBC patients (Hamilton et al, San Antonio Breast Cancer Symposium, 2020). Methods: The study evaluates the safety, pharmacokinetics (PK), and efficacy of H3B-6545 in combination with palbociclib in patients with ER+, HER2- metastatic breast cancer (MBC). The escalation phase enrolls patients with 2 or more prior therapies in the metastatic setting. Up to one prior chemotherapy and up to one prior CDK4/6 inhibitor were allowed. Results: As of January 31, 2021, 10 patients were enrolled; 7 in Cohort 1 (H3B-6545 300 mg QD and palbociclib 100 mg QD) and 3 in Cohort 2 (H3B-6545 300 mg QD and palbociclib 125 mg QD). One patient in Cohort 1 was not evaluable for dose limiting toxicity (DLT) assessment and no DLT was observed in the 6 evaluable patients. One patient discontinued study treatment because of progression and no patients discontinued study treatment due to adverse events (AE). Grade 3 or 4 neutropenia and thrombocytopenia were observed in 4 patients and 1 patient, respectively. One patient had grade 3 hypercalcemia, generalized muscle weakness, hypophosphatemia, fall, and anemia and one patient had grade 3 lipase increase. Four patients had grade 1 bradycardia or sinus bradycardia (asymptomatic) 1 patient had grade 2 sinus bradycardia (symptomatic, no intervention required). Preliminary PK analysis suggested no clinically relevant drug-drug interactions between H3B-6545 and palbociclib, to be confirmed with data from additional cohorts. Recruitment is currently ongoing in Cohort 2. Updated results will be presented. Conclusions: H3B-6545, in combination with palbociclib, was well-tolerated. Clinical trial information: NCT04288089.
Improved survival supports primary endocrine therapy in patients with hormone receptor positive/ HER-2 negative metastatic breast cancer.
Authors: Shenk Robert , Cao Lifen , Bliggenstorfer Jonathan T. , Martin James Michael , Miller Megan E. 
Published: June 2021

e13034 Background: Current ASCO guidelines recommend endocrine therapy as preferred primary treatment for hormone receptor positive (HR+) metastatic breast cancer (MBC). We assessed survival outcomes of HR+/HER2- MBC patients undergoing endocrine therapy with and without chemotherapy. Methods: The National Cancer Database was queried 2004-2016 for patients with de novo HR+/HER2- MBC. Exclusion criteria were treatment with surgery or radiation at the primary site and missing oncologic and follow up data. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression modes. Results: 19,317 patients met inclusion criteria, among whom 2,360 (12%) received no systemic therapy, 2,617 (14%) received chemotherapy only, 10,078 (52%) received endocrine therapy only and 4,262 (22%) received both chemotherapy and endocrine therapy. Patients treated with chemotherapy only more frequently had lung (38%, p<0.001) or liver (36%, p<0.001) metastasis while those undergoing endocrine therapy only presented primarily with bone metastasis (82%, p<0.001). Patients with multiple metastatic sites more often received endocrine therapy alone than combined therapy (44 vs. 25%, p<0.001). Median overall survival was similar after combination therapy and endocrine therapy, and poorest after chemotherapy alone (33.1 vs 31.4 vs 19.8 months, p<0.001). After controlling for patient, facility, and tumor characteristics, endocrine therapy alone provided superior survival benefit to chemotherapy only, though combination systemic therapy resulted in the greatest overall survival (p<0.001). Conclusions: Primary endocrine therapy provided significant survival benefit over chemotherapy alone for HR+/HER2- MBC. Though combination systemic therapy may be warranted in progressive disease, our results align with recommendations for endocrine therapy as first line treatment for HR+/HER2- MBC. [Table: see text]