bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term adjuvant versus neoadjuvant hormone therapy in localized prostate cancer: A pooled individual patient analysis of two phase III trials.
Authors: Spratt Daniel Eidelberg , Malone Shawn , Roy Soumyajit , Grimes Scott , Eapen Libni , Morgan Scott Carlyle , Malone Julia , Craig Julia , Dess Robert Timothy , Jackson William , Schipper Matthew J , Michalski Jeff M. , Lee W. Robert , Pisansky Thomas Michael , Feng Felix Y , Shipley William U. , Sandler Howard M. , Roach Mack , Sun Yilun , Lawton Colleen Anne 
Published: May 2020

5584 Background: The timing of systemic therapy in relation to radiotherapy (RT) is important in most malignancies. In contrast, androgen deprivation therapy (ADT) has largely been investigated in relation to its duration rather than its sequencing with RT. Herein, we conduct the first combined individual patient analysis of two phase III randomized trials to determine the optimal timing of ADT with RT in localized prostate cancer (PCa). Methods: Individual patient data was obtained from the Malone et al trial (JCO 2019), which randomized patients to receive neoadjuvant/concurrent or concurrent/adjuvant ADT for 6 months with prostate only RT. This was combined with the prostate only RT arms of RTOG 9413 that randomized patients to 4 months of neoadjuvant/concurrent or adjuvant ADT. The neoadjuvant/concurrent arms of both trials were combined into the “neoadjuvant” group, and the concurrent/adjuvant (Malone) and adjuvant arm (RTOG 9413) were combined in the “adjuvant” group. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Cumulative incidence of distant metastasis (DM), PCa-specific mortality (PCSM) and biochemical failure (BF) were calculated using the Fine-Gray method with non-PCa deaths as competing events. Late genitourinary (GU) and gastrointestinal (GI) toxicity are also reported. Results: The median follow-up was 14.9 years (yrs) and 1065 patients were included (n=531 neoadjuvant, 534 adjuvant). Groups were well balanced for all baseline characteristics. Adjuvant ADT was superior to neoadjuvant ADT in terms of BF (15yr: 33% vs 43%, HR: 1.37 (95%CI: 1.12-1.68), p=0.002), DM (15yr: 12% vs 18%, HR: 1.40 (95%CI: 1.00-1.95), p=0.04), and PFS (15yr: 36% vs 29%, HR: 1.25 (95%CI: 1.07-1.47), p=0.01). Adjuvant ADT yielded lower PCSM (15yr: 15% vs 20%, HR: 1.29 (95%CI: 0.95-1.75), p=0.10), but did not reach statistical significance. This approached statistical significance in high risk PCa (HR 1.39 (95%CI 1.00-1.93), p=0.053). OS was not significantly different between arms (15yr: 39% vs 34%, HR: 1.11 (95%CI: 0.95-1.30), p=0.20). There was no significant difference in either late grade ≥3 GI (p=0.21) or GU (p=0.98) toxicity. Conclusions: We demonstrate for the first time that sequencing of ADT with RT significantly impacts long-term oncologic outcomes in localized PCa, favoring an adjuvant rather than neoadjuvant approach, without increasing late toxicity. This data has important implications to ongoing and future clinical trial design. Clinical trial information: NCT00769548 .
Novel estrogen receptor beta agonist S-equol decreases tumor proliferation in patients with triple negative breast cancer (TNBC).
Authors: Lathrop Kate Ida , Kaklamani Virginia G. , Brenner Andrew Jacob , Li Rong , Nazarullah Alia , Hackman Sarah , Thomas Courtney , Gelfond Jonathan , Rodriguez Marisa , Elledge Richard 
Published: May 2020

560 Background: Patients with TNBC breast cancer have inferior treatment outcomes compared to other breast cancer subtypes and targeted therapies are lacking. S-equol is a novel oral Estrogen Receptor (ER) Beta agonist with preclinical data showing suppression of TNBC cellular proliferation. We therefore conducted an early phase window of opportunity trial to evaluate the impact of S-equol on Ki-67 change in patients with TNBC. Methods: This neoadjuvant window trial enrolled 39 patients with confirmed TNBC on diagnostic core needle biopsy. Cohort A (20 patients) received a daily dose of 50 mg daily and Cohort B (19 patients) received a higher dose of 150 mg daily. Paired biopsies were evaluable for 36 patients. Both cohorts were treated for a duration of 10-21 days. Primary outcome was change from pre- to post-treatment Ki-67 evaluated by paired t-test. All tests were 2-sided with a significance level of 0.05. Statistics were conducted within an accountable data analysis process in R (ADAPR). Secondary outcomes included toxicity and correlative biomarkers. Results: The mean (SD) pre-treatment was 68% (21.99) and post-treatment 59% (20.62). The average decrease in Ki-67 was 8% (P = 0.00206, 95% CI -13.46 to -3.26). A Ki-67 decrease of at least 20% from baseline was observed in 28% of the patients. S-equol was well tolerated with the most common toxicities being nausea, constipation, diarrhea, and headache. All toxicities were grade one. Treatment compliance was greater than 95%. Planned correlative studies included RNA-seq. A total of 161 genes are differentially expressed with fold change > = 2 and p value < 0.05. The top genes of the differential expression list include BMP5, S100A7, FABP7, SCGB2A2, CH507-338C24.1, and DUSP1. Gene Set Enrichment Analysis (GSEA) indicates that top enriched gene modules are related to interferon function and immune response, most of which are downregulated in the post-treatment group. Conclusions: S-equol is a novel well tolerated oral ER-Beta agonist with inhibition of proliferation in patients with TNBC as measured by a decrease in Ki-67. RNA-seq data supports potential immune activation during this short period of drug exposure. Future studies aim to evaluate S-equol as an immune activating agent for combination with immunotherapies such as checkpoint inhibitors in TNBC. Clinical trial information: NCT02352025 .
Can sentinel node biopsy after neoadjuvant systemic chemotherapy (NAC) be safely omitted in selected patient with early breast cancer?
Authors: Yoshida Atsushi , Kojima Yasuyuki , Tazo Mizuho , Matsuda Naoko , Tsugawa Koichiro , Yamauchi Hideko , Nakamura Seigo , Hayashi Naoki 
Published: May 2020

564 Background: There is a recent trend of performing minimum axillary surgery considering the prognostic value and fewer complications for primary breast cancer patients since the results of ACOSOG Z011. Nodal status after NAC is not be useful for postoperative treatment in most of cN0 patients. Therefore, sentinel node biopsy (SNB) may be omitted if ypN0 after NAC can be predicted in cN0 patients. We assessed clinicopathological factors associated with ypN0 after NAC in cN0 primary breast cancer patients. Methods: Two-institutional retrospective cohort study of clinically N0 breast cancer patients before NAC and who underwent breast surgery was conducted, including 419 consecutive patients between 2009 and 2016 in St. Luke's International Hospital and St. Marianna University School of Medicine hospital. Each institutional review board approved this study. In the patients with or without nodal metastasis on SNB after NAC, we compared clinicopathological factors including Estrogen Receptor (ER), Progesterone Receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 on needle biopsy specimens, and tumor size before and after NAC on MRI findings. Results: Of the 419 patients, 380 patients (90.7%) were ypN0 and 39 patients (9.3%) were ypN+ after NAC. In univariate analysis, clinical complete response of primary tumor on MRI findings (MRI-CR) (p<0.01), ER-negative (p<0.01), PgR-negative (p<0.01), and high-Ki-67 >30% (p<0.01) were significantly associated with ypN0 on SNB after NAC. In multivariate analysis, MRI-CR (HR 5.12, p<0.01) and high-Ki-67 (HR 2.86, p<0.01) were independent predictive factors of ypN0 after NAC.According to breast cancer subtype, only one of 72 ER-negative and HER2-positive had significantly low risk of ypN+ (1.3%) comparing other subtypes (p<0.01). Conclusions: Achieving cCR of primary tumor after NAC and high-Ki67 in cN0 patients, especially in HER2 type breast cancer, might have ypN0. We are conducting prospective study to omit SNB for these populations based on these results,
Establishing analytical and clinical similarity between HD201 and herceptin.
Authors: Hii Jocelyn , Pivot Xavier , Mclendon Kristi , Chan Kuo Wei , Feyaerts Peggy , Lee Jeong-Hyeon , Ang Felicia , Demarchi Martin , Coliat Pierre , Deforce Filip , Derde Marie_Paule , Kim Michael J , Park Lisa Soyeon 
Published: May 2020

579 Background: Trastuzumab, an approved prescription drug by EMA and FDA under the name Herceptin has become the key treatment in patients with HER2−positive breast cancer. HD201, developed by Prestige Biopharma Pte Ltd is a biosimilar candidate to Herceptin. The biosimilarity of HD201 was established based on systematic stepwise comparisons between HD201 and reference product, Herceptin. In order to confirm clinical similarity of HD201 to Trastuzumab, two clinical studies were undertaken. Methods: First, in a double-blind, randomised and parallel group study, 101 randomised healthy human subjects were subjected to a single 6 mg/kg IV dose by body weight over 90-min infusion of either HD201, EU- and US-Herceptin group by assessing pharmacokinetic (PK) and safety (TROIKA-I). The second study was a randomised, double-blind, parallel group, equivalence, multicentre clinical phase III trial (TROIKA) designed to compare the efficacy based on total pathological complete response rate (tpCR), safety, and pharmacokinetics of HD201 to EU-Herceptin in patients with HER2 positive early breast cancer. Each group of ~250 subjects were administered with either HD201 or EU-Herceptin in combination with chemotherapy in neoadjuvant followed by the antibody alone in the adjuvant phase. Results: TROIKA-I study demonstrated that HD201 was safe and well tolerated with comparable PK as EU- and US-Herceptin. Based on the neoadjuvant data from TROIKA study, the tpCR rate in the HD201 and Herceptin treatment groups was comparable and the 95% CI was included within the pre-defined margins of equivalence (Table). The incidence and severity of reported TEAEs did not imply any significant safety concerns and were comparable between both groups. In addition, the comparison of steady-state Ctrough between both arms in TROIKA study has established equivalence. Conclusions: The overall comparison exercise demonstrated the equivalence of HD201 to Herceptin. Clinical trial information: 2016-0040019-11 . [Table: see text]
The impact of pattern of tumor response and other post-treatment histologic features on local recurrence in patients treated with neoadjuvant chemotherapy and breast conservation.
Authors: Laws Alison , Pastorello Ricardo G. , Choi Jungeon , Kantor Olga , Grossmith Samantha , Schnitt Stuart J. , Golshan Mehra , Mittendorf Elizabeth A. , King Tari A. 
Published: May 2020

581 Background: Residual disease after neoadjuvant chemotherapy (NAC) is a poor prognostic factor. The relationship between the pattern of tumor response and other post-treatment histologic features on local recurrence (LR) is not well studied. Methods: We identified 380 patients (pts) treated with NAC, breast-conserving surgery and radiation from 2002-2014. Pts with available surgical slides underwent detailed pathology review. Pathologic complete response (pCR) was defined as no invasive or in situ disease in the breast or axilla. Pattern of tumor response was defined as: none, scattered, or concentric. The degree of treatment effect was categorized as: absent, mild or marked. Univariate (UVA) and multivariate analyses (MVA) were performed to identify factors associated with LR. Results: 243 (64%) cases had complete slides available and formed the study cohort. 76 (31%) were ER+/HER2-, 90 (38%) ER-/HER2- and 77 (31%) HER2+. 98% of HER2+ pts received neoadjuvant trastuzumab; 89% of ER+ pts received adjuvant endocrine therapy. At median follow-up of 75 months, 10/243 (4.1%) pts had LR and 5-yr LR-free survival was 95.7%. LR occurred in 1/76 (1.3%) pts with breast pCR, 1/19 (5.2%) with residual DCIS, and 8/148 (5.4%) with residual invasive disease; including 6/78 (7.7%) with scattered tumor response, 2/46 (4.3%) with concentric response and 0/24 with no response. On UVA, age (OR < 50 vs ≥50 5.9, p = 0.03) and residual DCIS with comedonecrosis (OR 8.2, p < 0.01) were significantly associated with LR. Presence of tumor bed at the margin (OR 4.6, p = 0.06) approached significance. The odds of LR were higher with scattered regression (OR 1.83 vs. concentric, p = 0.47) and lower with breast pCR (OR 0.23, p = 0.17), but these results were not statistically significant. Multicentric disease, receptor status, ypT, ypN, RCB score, degree of treatment effect, high-grade residual invasive disease, margin status of residual disease and lymphovascular invasion were not associated with LR (all p > 0.05). Age (OR < 50 vs ≥50 7.4, p = 0.04) and residual DCIS with comedonecrosis (OR 7.5, p = 0.02) remained significant on MVA. Conclusions: With modern systemic therapy, LR rates after NAC, breast-conserving surgery and radiation are low, with less than 5% of patients experiencing a LR after a median follow-up of over 6 years. Young age and residual DCIS with comedonecrosis were associated with LR, but not pattern of tumor response.
Neoadjuvant TCH (docetaxel/darboplatin/trastuzumab) versus EC-TH (epirubicin/cyclophosphamide followed by docetaxel/ trastuzumab ) in patients with HER2-positive breast cancer (neoCARH): A randomised, open-label, multicenter, phase II trial.
Authors: Gao Hong-Fei , Wu Zhiyong , Lin Ying , Song Xiangyang , Cao Yin , Liu Zhenzhen , Chen Qian-Jun , Zhang Liulu , Yang Ci-Qiu , Yang Mei , Zhu Teng , Li Jieqing , Ji Fei , Cheng Min-Yi , Wang Kun 
Published: May 2020

585 Background: The optimal neoadjuvant treatment for HER2-positive breast cancer is unknown. We wanted to compare the efficacy and safety of the anthracycline regimen EC-TH versus nonanthracycline regimen TCH in neoadjuvant setting for HER2-positive breast cancer. Methods: Patients with stage II or III HER2-positive breast cancer were randomly assigned to either four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel and trastuzumab (EC-TH) every 3 weeks during all chemotherapy cycles, or six cycles of docetaxel and carboplatin plus trastuzumab (TCH) every 3 weeks. The primary endpoint was pathological complete response (defined as the absence of invasive tumour cells in breast and axilla, ypT0/is ypN0). This trial is registered with ClinicalTrials.gov, number NCT03140553. Results: From September 2016 to November 2019, 140 patients were randomly assigned, and 131 were evaluable for the primary end-point. The pathological complete response was recorded in 25 (38.5%, 95% confidence interval [CI] 26.6–50.2) of 65 patients in the EC-TH group and in 37 (56.1%, 44.1–68.0) of 66 in the TCH group (p=0.044). In the EC-TH group, 15 (23.1%) of 65 patients underwent breast-conserving surgery. In the TCH group, 21 (31.8%) of 66 patients underwent breast-conserving surgery. There was no difference in the proportions of patients undergoing breast-conserving surgery between the two treatment groups (p=0·262). The most common adverse events were neutropenia (in 23 [35.4%] of 65 patients in the EC-TH group vs 27 [40.9%] of 66 in the TCH group), anemia(in 33 [50.8%] of 65 patients in the EC-TH group vs 34 [51.5%] of 66 in the TCH group) and thrombocytopenia (in 5 [7.7%] of 65 patient in the EC-TH group vs 17 [25.8%] of 66 in the TCH group). Conclusion: This is the first multicenter prospective randomised phase II trial compare EC-TH with TCH for neoadjuvant therapy in HER2-positive breast cancer. There was a similar incidence of AEs but a higher pCR rate in TCH arm compared with the EC-TH arm. TCH regimen might be a preferred approach in patients with HER2-positive breast cancer. Long-term follow-up is required to confirm these results. Clinical trial information: NCT03140553 .
Neoadjuvant docetaxel + carboplatin versus epirubicin+cyclophosphamide followed by docetaxel in triple-negative, early-stage breast cancer (NeoCART): Results from a multicenter, randomized controlled, open-label, phase II trial.
Authors: Zhang Liulu , Wu Zhiyong , Lin Ying , li jie , Liu Zhenzhen , Cao Yin , Zhang Gangling , Gao Hong-Fei , Yang Mei , Yang Ci-Qiu , Zhu Teng , Cheng Min-Yi , Ji Fei , Li Jieqing , Wang Kun 
Published: May 2020

586 Background: Taxane- and anthracycline-based neoadjuvant regimens have become a standard treatment for triple-negative breast cancer (TNBC). Previous studies have shown that adding carboplatin to neoadjuvant chemotherapy regimens significantly improved pCR rate in TNBC patients. The NeoCART study was designed to compare the efficacy and safety of docetaxel plus carboplatin with standard neoadjuvant chemotherapy in TNBC. Methods: NeoCART was designed as a multicenter, randomized controlled, open-label, phase 2 trial. The patients enrolled were at least 18 years old with previously untreated stage II-III (T1cN1-2 or T2-4N0-2) invasive TNBC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. All eligible patients were randomly assigned, in a 1:1 ratio, to the experimental arm (docetaxel (75 mg/m2) plus carboplatin (AUC 6) for six cycles) or the standard treatment arm (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 four cycles, followed by docetaxel 100 mg/m2 for four cycles). The primary end point was the pCR rate (ypT0/is and ypN0). Secondary endpoints included event-free survival, frequency of breast-conserving surgery, and safety. Results: Between September 1, 2016, and December 31, 2019, 88 patients from 6 participating centers were included and randomized (44 patients to the DCb arm and 44 to the EC-D arm). In the primary end point analysis, 27 patients (61.4%, 95% CI 47.0 - 75.8) in the DCb group achieved a pCR compared with 17 patients (38·6%, 95% CI 24.3 - 53.0) in the EC-D group (odds ratio 2.52, 95% CI 2.4 - 43.1; p = 0.033). In different stage disease, the pCR rates of the DCb and the EC-D groups were 73.3% (22/30) vs 48.4% (15/31) in stage II (p = 0.046), and 35.7% (5/14) vs 15.4% (2/13) in stage III (p = 0.384). In patients with axillary lymph node involvement, the pCR rates were 45.8% (11/24) vs 30.8% (8/26) (p = 0.273); and 80.0% (16/20) vs 50.0% (9/18) with lymph node negative disease (p = 0.052). The frequency of breast-conserving surgery in the DCb and EC-D groups was 36.4% and 37.2%, respectively (p = 0·935). The grade 3/4 adverse events include anemia (4.5%), thrombocytopenia (2.3%), neutropenia (2.3%) and ALT/AST increased (2.3%) in the DCb group. Conclusions: Compared with the standard neoadjuvant regimen, docetaxel combined with carboplatin showed a higher pCR rate in TNBC. The higher pCR rate was more significant in patients with earlier disease stage and negative lymph node. Clinical trial information: NCT03154749 .
12-chemokine gene expression score in breast cancer patients treated with neoadjuvant chemotherapy.
Authors: Soliman Hatem Hussein , Prabhakaran Sangeetha , Rosa Marilin , Cox Charles E. , Whitworth Pat W. , Uygun Sahra , Kling Heather M. , Yoder Erin , Audeh William 
Published: May 2020

591 Background: Although advances in immunotherapy for the treatment of breast cancer have been minimal compared with other cancers, studies demonstrating tumor-infiltrating lymphocytes and immunomodulatory gene activation in the tumor microenvironment suggest the importance of antitumor immune responses in clinical outcomes. A 12-chemokine gene score has been shown to predict the presence of ectopic lymph node-like structures (ELN) in the tumor microenvironment and improved survival in melanoma, colon cancer, and breast cancer patients (Prabhakaran, 2017). Here, we evaluated this signature in an independent dataset of breast cancer patients treated with neoadjuvant chemotherapy. Methods: Tumor specimens used in this retrospective analysis (n = 92) were from breast cancer patients enrolled in either MINT (NCT0151487) or NBRST (NCT01479101) neoadjuvant registry trials from 2011 to 2016. Clinical data were captured with informed consent, and 70-gene signature (70-GS), 80-gene signature (80-GS), and full transcriptome data were generated by Agendia, Inc. Gene expression data were quantile normalized using R limma package. Principal component analysis (PCA) was performed on the normalized dataset using R princomp package. Chemokine score (CS) was defined as the first principal component values resulting from PCA. 70-GS/80-GS and clinical data were evaluated in relation to CS. CS were compared using Mann-Whitney test. Results: Of 92 breast tumors available for analysis, 84% were 70-GS High Risk (HR). Tumors were 39% Luminal-type, 24% HER2-type, and 32% Basal-type by 80-GS. HR tumors had higher CS than 70-GS Low Risk (LR) tumors (p < 0.001). 80-GS Basal-type, HER2-type, and Luminal B tumors had higher CS than Luminal A tumors (p < 0.01 for each comparison). High grade and ER-negative tumors seemed to have a high CS, although not significantly. Tumors from patients who achieved a pathological complete response (pCR) following neoadjuvant chemotherapy had higher CS than patients with residual cancer burden (p = 0.048). Conclusions: The current study demonstrated a significantly higher CS in 70-GS HR tumors and those which achieved pCR following neoadjuvant chemotherapy. Although further study is needed to evaluate the association of high CS with tumor-associated ELN, these results support previous work demonstrating that, although high CS is associated with aggressive clinical features, it also predicts superior clinical outcomes. The current study suggests validation of the 12-chemokine gene score in an independent dataset of breast cancer patients.