bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of tumor size on nodal disease burden in clinically node negative breast cancer.
Authors: Lee Minna K. , Rubenstein Robyn , Sevilimedu Varadan , Montagna Giacomo , Shamsunder Meghana , Nelson Jonas A. , Le Tiana , Garcia Paula , Morrow Monica , Tadros Audree 
Published: June 2022

e12575 Background: Randomized trials have shown no difference in outcomes for cT1-2N0 breast cancer patients with 1-2+ sentinel lymph nodes (SLNs) undergoing sentinel lymph node biopsy (SLNB) alone compared to axillary dissection (ALND). No studies have yet evaluated whether these results can be applied to cT3N0 patients. Our objective was to evaluate nodal burden in cT3N0 compared to cT1-2N0 patients. Methods: Patients with cT1-3N0 breast cancer undergoing upfront surgery were identified from the National Cancer Database (NCDB) from 2012 through 2017. Analysis was limited to those with ≥ 3 lymph nodes (LNs) retrieved. Clinical and pathologic characteristics were examined using Wilcoxon Rank sum tests, Chi square, or Fisher’s exact tests. Univariate and multivariable logistic regression analyses were performed to examine characteristics associated with increased nodal burden (≥ 3 +LNs). Results: During the study period, we identified 198,137 cN0 patients with ≥ 3 LNs retrieved, of which 191,672 (97%) were cT1-2 and 6,465 (3%) were cT3. Most patients had ductal histology (83%) and ER+/HER2- subtype (83%). Of cT1-2 patients, 7% (13,902/191,672) had ≥ 3 +LNs compared to 28% (1,791/6,465) of cT3 patients. Among patients with ≥ 3 +LNs, the majority (91%) underwent ALND with a median of 14 (interquartile range [IQR] 9,19) LNs retrieved. Of these patients, cT3 disease was associated with an increased number of +LNs compared to cT1-2 disease (median [IQR], 6 [4,10] vs. 4 [3,7], p<0.01). On multivariable analysis, invasive lobular carcinoma (ILC) (OR 2.11, 95% CI 1.34-3.30), lymphovascular invasion (LVI) (OR 5.22, 95% CI 4.43-6.16), and pathological tumor size > 8 cm (OR 2.76, 95% CI 2.16-3.53) were independently associated with ≥ 3 +LNs in cT3 patients. Triple-negative breast cancer (TNBC) was associated with lower odds of ≥ 3 +LNs (OR 0.50, 95% CI 0.36-0.68). In those with tumors 5-8 cm in size, 364 (27%) of 1,363 patients with IDC had ≥ 3 +LNs, compared to 152 (48%) of 315 patients with ILC. Conclusions: cT3N0 patients have increased nodal burden compared to cT1-2N0 patients. Caution should be used in extrapolating guidelines for cT1-2N0 patients to high-risk cT3N0 patients with large tumors, LVI, and lobular histology.[Table: see text]
Real-life analysis of pathologic complete response with neoadjuvant trastuzumab plus taxane with or without pertuzumab therapy in HER2 positive locally-advanced breast cancer (HER2PATH Study).
Authors: Bilici Ahmet , Olmez Omer Fatih , Sezer Ahmet , Oksuzoglu Berna , Kaplan Muhammet Ali , Karadurmus Nuri , Cubukcu Erdem , Sendur Mehmet A.N. , Aksoy Sercan , Erdem Dilek , Basaran Gul , Cakar Burcu , Seker Mesut , Arslan Cagatay , Sezgin Goksu Sema , Cicin Irfan , Gumus Mahmut , Selcukbiricik Fatih , Harputluoglu Hakan , Helvaci Kaan 
Published: June 2022

e12610 Background: Studies in HER2+ locally-advanced breast cancer (LABC) patients with neoadjuvant dual HER2 blockage therapy demonstrated high rates of pathologic complete response (pCR). This study evaluates neoadjuvant chemotherapy (NCT) plus trastuzumab (H) with or without pertuzumab (P) therapy with a nation-wide real world setting. Methods: In this study, 1528 female HER2+ LABC patients’ data received NCT plus H with or without P were collected retrospectively from 21 centers. Ethics committee approved the study (NCT04765124). Primary end point was pCR rate (ypT0/Tis ypN0 in the current AJCC staging system). Results: Of the 1528, 951 (62.2%) were received NCT-H, 577 (37.8%) were received NCT-HP, follow-up durations were 30 months and 15 months, median ages were similar between 2 groups (47 years, range: 20-81 and 47 years, range 22-88, respectively). According to the menopausal and hormone receptor status 60% and 53.7% of patients were classified as premenopausal, 56% and 57.8% as estrogen receptor positive and 46.2% and 47.2% as progesterone receptor positive respectively at NCT-HP and NCT-H groups. Despite the patients at NCT-HP group mostly received docetaxel (75%), NCT-H group received weekly paclitaxel (59.4%) as taxane (p<0.001). pCR rate for patients treated with NCT-HP was significantly better than that for patients received NCT-H (66.4% vs. 56.8%, respectively, p<0.001) and there were not any statistical difference according to hormone receptor status. Two-years event-free survival (EFS) rates were 93.5% and 93.2% for NCT-HP and NCT-H groups, respectively (p=0.655), however, two years EFS rate was statistically significant in patients who achieved pCR compared to those who did not achieve pCR (95.1% vs. %90.6, p<0.001). There was not any toxicity leading to death. Conclusions: Our analysis of this real world data shows higher rates of pCR than in clinical trials, also adding pertuzumab to NCT-H demonstrates higher pCR rates and EFS rates compared with NCT-H in patients with HER2+ LABC.
HDAC inhibitor Tucidinostat plus exemestane as neoadjuvant therapy in patients with hormone receptor positive, HER2 negative breast cancer.
Authors: Wang Xin ,   Tianjin Medical University Cancer Institute and Hospital
Published: June 2022

e12623 Background: Tucidinostat (formerly known as chidamide) is an oral subtype-selective histone deacetylase (HDAC) inhibitor with demonstrated efficacy and safety in combination with exemestane in postmenopausal patients with advanced, hormone receptor-positive breast cancer. The aim of this study was to evaluate the efficacy of tucidinostat combined with exemestane as neoadjuvant strategy in hormone receptor-positive early breast cancer patients. Methods: The study (ChiCTR2100046678) is a single-center, prospective, open-labeled, single-arm phase II study. Patients with HR-positive, HER2-negative, and node-positive, stage II–III breast cancer were enrolled at Tianjin Medical University Cancer Institute and Hospital. Eligible patients received 30 mg oral tucidinostat twice weekly in combination with 25 mg oral exemestane daily for up to a total of 24 weeks. The primary endpoint was to determine percent of pts who achieve a PEPI score of 0. The secondary endpoints were to analyze the the pathological complete remission (pCR) rate, complete cell cycle arrest (CCCA, defined as Ki67<2.7%), objective response rate (ORR), disease control rate (DCR) and event free survival (EFS), and overall survival (OS) as well as the safety and tolerability. Results: Patient enrollment initiated in Jan. 2021 and ended in Nov. 2021. Of the 20 pts enrolled, 20 were treated and radiologically evaluable for response. The ORR was 40% with CR 5% (n=1) and PR 35% (n=7). The DCR was 100%. Four patients were still on wait lists for surgery. Of the 16 pts with surgery, one case achieved pCR. The follow-up remains ongoing and updated results will be presented thereafter. Most adverse events (AEs) were grade 1 or 2. Grade 3 AEs included neutropenia (11.8%), thrombocytopenia (5.9%) and lung infection (5.9%), respectively. Conclusions: The combination of Tucidinostat and exemestane was well tolerated with encouraging clinical responses in early hormone receptor positive, HER2 negative breast cancer. Further investigation is warranted. Clinical trial information: ChiCTR2100046678.
Neoadjuvant therapy with concurrent anthracyclines and taxanes in Her2-negative breast cancer (HNBC): TAC legacy.
Authors: García Samblás Victoria , David Morales Pancorbo , Aragon Manrique Isabel , Bayo Juan L. 
Published: June 2022

e12629 Background: Adyuvant therapy with Concurrent docetaxel-adriamycin-cyclophosphamide (TAC) increases overall survival in positive node breast cancer. However it is associated with an increased risk of infection and cardiotoxicity. Switching to epirubicin (TEC) and adding Filgrastim prophylaxis (GCSF) could be an useful and safe option in the neoadjuvant setting. Methods: We reviewed the efficacy and safety of neoadjuvant regimen TEC x 6 cycles(c) and GCSF in HNBC. Kaplan–Meier, Cox regression and binary logistic regression were performed to analyze survival prognostic factors, pathological complete response rate (pCR) and serious adverse events. Results: From 2015 to 2021, 204 patients (pt) and 1125 cycles were registered. Median follow-up of 39.4 months. Median age 48 years (SD 8.3), stage II to IIIC (35% IIB), 64% were positive node and 25% Triple Negative(TN) tumors. A median dose of 90% (87.9-93.4) was administered, 93% with a cumulative dose higher than 66% (equivalent to 4 c). Radiologic response in 75% pt. 16.3% pt achieved pCR (3.2% in LumA, 15% in LumB and 35% in TN tumors). OR 4.98 (2.18-11.35) for TN and OR 0.94 (0.89-0.99) for older p<0.05. No relapses were detected in TN patients with PCR. PCR was non-inferior in pt who received 66% of planned dose (OR 1.3, p=0.76) and was higher in LumB than LumA, OR 5.2 (1.13- 24.61), p <0.05. Lymphadenectomy was avoided in 29.2% of patients with affected node at baseline. 3 years (y) relapse free (F) survival (S) of 86.1% (91-80%), better prognosis in stage II HR 0.29 (0.14-0.58) and older HR 0.93 (0.89-0.98), p< 0.005. 3y overall FS of 89% (93-84%), worse prognosis in TN with HR 3.48 (1.37-8.84). Lower risk in stage II with HR 0.31 (0.13-0.75) and in Pegfilgastrim with HR 0.14 (0.03-0.67), p<0.05. Hospital admissions in 24% for any cause. Older age (OR 1.05, p=0.01). 21% neutropenia G3/4. Infections in 17.2% of pt. Febril neutropenia in 18.1%, no related to age (p=0.5) or pegfilgrastim Vs filgrastim (p=0.99). Asthenia 17%, colitis 6% and thrombosis in 2%. No cardiacs events were reported. Conclusions: TEC is effective in the neoadjuvant setting of HNBC. It has similar pCR and survivall to those reported in meta-analysis. GCSF facilitates treatment compliance but the risk of neutropenia and admissions are still present. A lower cumulative dose could be enough to achieve the same results. Stage III and TN have shown a worse prognosis.
The decline of circulating tumor cell clusters count for predicting the treatment response in breast cancer patients.
Authors: Chou Hsu-Huan , Che Ting-Fang , Chen Shin-Cheh , Tsai Chi-neu , Chang Ying , Chen Fang Ming 
Published: June 2022

e13009 Background: Circulating tumor cells (CTCs) are the precursors of metastatic cancer because they originate from primary tumor sites into the vascular system. The prognostic information of CTCs was well established in breast cancer treatment while the predictive value was still unclear. The aim of this study was to analyze the predictive value of CTCs count during treatment. Materials and Methods: A prospective study was conducted from 2019 to 2021, and 31 female breast cancer patients were enrolled, and 54 blood samples were collected at Linkou Chang Gung Memorial Hospital. The median age was 47 years old. We used LIPO platform for CTC isolation with anti-EpCAM antibody. To achieve maximum cellular viability, the LIPO platform was further optimized by using liposomes-lipid bilayers instead of lipid bilayers as the underneath surface coating to facilitate the detachment of bound cells from the surface and maintain cellular viability. Results: Fourteen patients were Stage II or stage III (non-metastasis) and 17 metastatic patients were included. Eleven patients (35.5%) were ER-positive HER2-negative while 10 patients (32.6%) were ER-positive HER2-positive. Three patients (9.7%) were HER2 enriched subtypes, and 7 patients (22.6%) were triple negative breast cancer. Blood samples from a total of 28 patients can be analyzed. At least one CTC was detected in 44/49 (89.8%) blood samples, CTC can’t be identified in 2/5 (40%) post-treatment with good response. The average single CTC count per 2 ml was 34.40 in non-metastatic patients versus 110.43 in metastatic patients (p = 0.3895). The average clustered CTC count per 2 ml was 13.44 in non-metastatic patients versus 40.16 in metastatic patients (p = 0.424). The total single and clustered CTC count per 2 ml was 47.84 non-metastatic patients versus 150.59 in metastatic patients (p = 0.3977). In 10 patients with clinically partial response, the average single CTC count per 2 ml was 61.9 before treatment and 11.81 after treatment (p = 0.0716), and the average clustered CTC per 2 ml was 15.83 before treatment and 5.28 after treatment (p = 0.8806). In 4 patients with clinical progression, the average single CTC count per 2 ml was 22.694 before treatment and 26.125 after treatment (p = 0.0257), and the average clustered CTC per 2 ml was 7.69 before treatment and 16.61 after treatment (p = 0.3798). Conclusions: Our findings concluded that the decline of circulating tumor cell clusters count can predict the treatment response in breast cancer patients.
Effectiveness and safety of eribulin as a front-line treatment in advanced breast cancer patients in China: A prospective real-world study.
Authors: Zhao Jian-Li , Dinglin Xiao-Xiao , Yang Ya-Ping , Luo Si-Min , Cai Yang-Yang , Chai Jie , Liu Dong-Geng , Wang Ying , Yao He-Rui 
Published: June 2022

e13015 Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. However, the efficacy and safety data of eribulin for the ABC in Chinese patients is lacking, whether as first, second, or third-line regimens. This study aimed to evaluate the clinical effectiveness, safety, and treatment pattern of eribulin in first to third-line settings in Chinese ABC patients. Methods: Patients with histologically confirmed advanced breast cancer, who previously received ≤2 lines of treatment for metastatic disease were enrolled. In HR+/HER2- ABC, eribulin monotherapy was used; in HER2+ ABC, eribulin plus anti-HER2 targeted therapy were used; in metastasis triple-negative breast cancer (mTNBC), eribulin plus immunotherapy/chemotherapy were used. Primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: Forty-seven patients were enrolled from 2021.1.1 to 2021.10.20, including 41 metastatic and 6 de novo ABC patients. Eribulin was used as first-line therapy in 12 (25.5%) patients, second-line therapy in 24 patients (51.1%), and third-line therapy in 11 (23.1%) patients. More than 90% of the patients did not receive gemcitabine or vinorelbine, and 30.0% of them did not receive anthracycline or taxane previously. DCR was 70.2%, as 24 cases (51.1%) had stable disease and 9 cases (19.1%) had complete or partial remission. In subgroup analysis, median PFSs of 9.6 (95% CI: 6.5-12.7), 7.1 (95%CI: 4.4-9.8), and 5.6 (95%CI: 3.8-7.5) months were observed in patients receiving eribulin as first-, second-, and third-line therapy, respectively. In addition, median PFSs were 7.1 (95% CI: 5.1-9.3), 9.6 (95%CI: 3.6-15.7), 4.6 (95%CI: 4.6-4.6) and 5.8 (95%CI: 4.4-7.3) months for HR+/HER2-, HR+/HER2+, HR-/HER2+, and mTNBC patients, respectively. Other results from the subgroups analysis were shown in table. Common treatment-related toxicity was hematological toxicities including leukopenia (23%), neutropenia (17%), and thrombocytopenia (10%). There was no ≥grade 3 adverse events and no adverse event-related treatment discontinuation. Conclusions: Eribulin monotherapy or combined with targeted therapy was effective and well-tolerated as the first to third lines of treatment in ABC. This promising therapeutic outcome might warrant further studies in early eribulin administration in ABC patients. Clinical trial information: NCT04683445. [Table: see text]
28-gene classifier model for prediction of local recurrence and distant metastasis risk in HER-2 positive operable breast cancer.
Authors: Kang Yikun , Wang Huimin , Ding Ran , Xu Binghe , Yuan Peng 
Published: June 2022

e13018 Background: Accurate prediction of postoperative recurrence risk is very important for the formulation of appropriate treatment for breast cancer patients. However, traditional clinicopathological indicators cannot accurately assess the recurrence risk of patients. We aimed to build a novel gene-clinical variable model, which included 28 genetic profiles and clinical variable information, to assess the risk of recurrence in a more individualized and accurate manner. Methods: We retrospectively included a cohort of operable HER-2 positive breast cancer patients treated in Cancer Hospital of the Chinese Academy of Medical Sciences from 2010 to 2016. The genetic and clinical data were used to train and validate the 28-gene classifier model in predicting local recurrence and distant metastasis risk. Results: A total of 260 HER-2 positive breast cancer patients were Included in the study. All patients received standard adjuvant chemotherapy and routine targeted therapy after mastectomy. All patients were followed up for a median of 60.4 months for disease recurrence. Among them, 21 patients had distant metastasis events and 18 patients had local recurrence events. We used the 28 gene-clinical variable model to classify 260 patients into high- and low-risk groups. Kaplan-Meyer survival curves were used to compare the prognostic difference of DFS into high- and low- risk groups. Conclusions: 28 gene-clinical variable model may be a reliable toll to predict local recurrence and distant metastasis risk in HER-2 positive operable breast cancer.
Association of intrathecal trastuzumab to standard therapy in patients with leptomeningeal metastasis in HER2 positive breast cancer.
Authors: Trifanescu Oana Gabriela , Gales Laurentia Minea , Ciornei Ana , Mitrea Dan , Anghel Rodica Maricela 
Published: June 2022

e13021 Background: Leptomeningeal metastases are rare but fatal manifestation of metastatic breast cancer, especially in HER2 positive sub-type, with limited treatment options and median overall survival in the range of only 4-6 weeks in untreated patients. Methods: Our prospective study included 9 patients with HER2 positive breast cancer with leptomeningeal metastases that received intrathecal treatment with Trastuzumab along with systemic therapy. Data was compared with a control lot of 9 patients with leptomeningeal metastasis that did not receive intrathecal treatment. Radiotherapy was administered in all patients. The patients included in the study received cures of 150 mg of Trastuzumab injected intrathecal every 3 weeks. Results: Median age of the patients at the time of diagnosis was 53 years. Median time from diagnosis of BC until diagnosis of leptomeningeal carcinomatosis was 3.4 years. Median progression free survival for patients receiving trastuzumab intrathecal was 11.1 months compare with 6.4 months in patients receiving standard treatment, p < 0.019. In our lot of patients, response rate was 66.6%. A clinical benefit with symptoms relief was observed in 77.7% of patients. Mean number of administrations was 12. Two patients presented pain and in two instance the administration was not possible. Concurrent systemic treatment consisted in lapatinib and capecitabine (22.2%), trastuzumab emtansine (44.5%), tucatinib combination (22.2%), vinorelbine (11.1%) and no unexpected toxicity to systemic treatment was noticed. Conclusions: Intrathecal administration of trastuzumab along with systemic treatment and radiotherapy, might improve or stabilise the consequences of leptomeningeal involvement by HER2-positive breast cancer with manageable toxicity.
The CDK4/6 inhibitor FCN-437c plus letrozole for the treatment of HR+/HER2– advanced breast cancer: Updated results from a phase 1b study.
Authors: Zhang Jian , Wang Xiaojia , Wang Xian , Li Wei , Cheng Ying , Huang Tao , Wang Ying , Hui Ai-Min , Wu Zhuli , Tian Ling , Zhao Han , Yang Yuchen , Zhang Wenjing , Zhang Yushun , Hu Xichun 
Published: June 2022

e13025 Background: FCN-437c is an oral potent and highly selective CDK4/6 inhibitor without the inhibition of CDK1, CDK2, or CDK5. In the phase 1a dose-escalation part of this study (NCT04488107), the safety profile of FCN-437c was acceptable in patients with ABC, and the maximum tolerated dose was determined to be 300 mg QD when used as monotherapy (presented at AACR 2021). Phase 1b aimed to explore the RP2D and to evaluate the tolerability and antitumor activity of FCN-437c combined with letrozole in patients with previously untreated HR+/HER2– ABC. Methods: Adult, post-menopausal female patients diagnosed with treatment-naive ER+/HER2– ABC were eligible for this expansion stage. Patients received FCN-437c once daily at 200 mg or 300 mg on a 21-day-on and 7-day-off schedule in combination with letrozole 2.5 mg once daily in 28-day cycles. The primary endpoints were safety and RP2D. Results: As of November 26, 2021, 29 patients were enrolled and had a median follow-up of 10.4 months. Of these patients, 25 (86.2%) were endocrine-sensitive and 4 (13.8%) were endocrine-resistant. Visceral disease was present in 21 patients (72.4%), and 1 (3.4%) patient had bone-only disease. DLTs of grade 4 neutropenia occurred in 2 patients (40.0%) in 300 mg dose group; they were considered intolerable. One out of the first 6 patients experienced DLTs in 200 mg dose group (grade 4 neutropenia, leukopenia, and thrombocytopenia); these were also considered to be FCN-437c-related SAEs. FCN-437c-related grade ≥3 TEAEs were observed in 26 (89.7%) patients, with neutropenia (n=24, 82.8%) and leukopenia (n=14, 48.3%) being most common. Among the 28 measurable patients, 16 patients had a PR, the ORR was 57.1% (95% CI 37.2–75.5); the CBR was 82.1% (95% CI 63.1–93.9) (Table). Median PFS, DOR, and OS were not reached. At 6 and 12 months, PFS rates were 92.3% and 83.5%, and DOR rates were 100% and 90%, respectively. A RP2D of 200 mg was suggested per safety considerations and preliminary antitumor activity. Conclusions: FCN-437c plus letrozole was well tolerated and demonstrated antitumor activity in patients with previously untreated HR+/HER2– ABC. FCN-437c in combination with NSAI as the first-line treatment for HR+/HER2– ABC will be further investigated in a phase 3 trial. Clinical trial information: NCT04488107. [Table: see text]