bluuebunny/crossref_metadata_2025_split huggingface dataset:
National trends in neoadjuvant chemotherapy utilization for cT1-2 N0 triple negative breast cancer: Did the CREATE-X trial impact treatment patterns?
Authors: Rogers Christine , Lloren Jan Irene , Johnson Morgan K. , Cobb Adrienne , Chaudhary Lubna Naaz , Huang Chiang-Ching , Teshome Mediget , Singh Puneet , Kong Amanda L. , Cortina Chandler Scott 
Published: June 2023

e12599 Background: Neoadjuvant chemotherapy (NAC) for operable breast cancer allows for in-vivo assessment of chemotherapy response with survival and therapeutic implications. In 2017, the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial demonstrated significant improvement in survival with the addition of adjuvant capecitabine in patients with triple negative breast cancer (TNBC) and residual disease after NAC. These results provided the rationale for NAC even in early stage TNBC. The aim of this study was to assess U.S. national rates of NAC utilization in early-stage node-negative TNBC patients before and after the release of CREATE-X and to assess factors associated with receiving NAC vs adjuvant chemotherapy (AC). Methods: The National Cancer Database was queried for women with cT1-2N0M0 TNBC from 2014–19. NAC utilization was collected and categorized as 2014-15 (pre-CREATE-X), 2016-17 (transition yrs), and 2018-19 (post-CREATE-X). Those who did not receive chemotherapy were excluded. NAC use over time was analyzed via multivariable logistic regression (MLR). Clinical and demographic factors associated with NAC vs AC utilization were assessed using ANOVA, Chi-squared, and Fisher Exact tests. A MLR model was used to determine predictors of receipt of NAC vs AC. Results: 55,633 women were treated from 2014-19: 26.9% with NAC, 52.4% with AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71yrs, respectively, p < 0.01). Most had cT1c (32.7%, n = 18,190) or cT2 (41.95%, n = 23,331) tumors and 99% had invasive ductal pathology. NAC utilization significantly increased over time, 19.5% (n = 3,465 of 17,777) in 2014-15, 27.1% (n = 5,140 of 18,985) in 2016-17, and 33.6% (n = 6,337 of 18,871) in 2018-19 (p < 0.01). On MLR analysis, increased use of NAC was associated with younger age ( < 50yrs), non-Hispanic white patients, having no comorbidities, having a cT2 tumor, grade 2 disease, and care at an academic or integrated network cancer program (p < 0.05 for all). Patients with Medicare and Medicaid insurance were less likely to receive NAC (p < 0.01). Patients who traveled > 60 miles to their treating facility were more likely to receive NAC (p < 0.01). Conclusions: From 2014–19, NAC utilization increased for patients with cT1-2N0M0 TNBC coinciding with the release of the CREATE-X results. Findings demonstrate the significance of the multidisciplinary oncology team in developing individualized treatment plans based on emerging clinical trial evidence. Racial, socioeconomic, and access disparities were observed in NAC utilization and warrants further investigation and interventions to ensure equitable care. [Table: see text]
Magnetic resonance imaging tumor regression shrinkage patterns during neoadjuvant chemotherapy versus neoadjuvant immunochemotherapy in triple-negative breast cancer (NeoMDSS-TN-SP): A nonrandomized, prospective cohort study.
Authors: Zhang Liulu , Zou Jiachen , Chen Yuanqi , Yan Xinjian , Wang Kun 
Published: June 2023

e12601 Background: Previous studies have shown that the tumor regression shrinkage pattern (SP) of triple-negative breast cancer (TNBC) during neoadjuvant chemotherapy (NAC) is more likely to present with concentric shrinkage (CS), which is associated with a pathological complete response (pCR). Since immunotherapy and chemotherapy have different antitumor mechanisms, it is reasonable to believe that there may be different SPs between neoadjuvant immunochemotherapy (NAIC) and NAC. This NeoMDSS-TN-SP prospective study aimed to investigate whether tumor SPs differed between NAIC and NAC in TNBC, as well as to calculate the correlation between SP and efficacy. Methods: In this prospective, single-center, nonrandomized cohort study, eligible patients with stage II-III TNBC received NAIC or NAC and underwent MRI at baseline, after the first cycle of neoadjuvant therapy, and preoperatively. Based on the MRI after the first cycle, the tumor SPs were grouped into three categories: CS, diffuse decrease, and no change or enlargement. The primary end point was the difference in SP between the two treatment groups. Secondary endpoints included the correlation between SP and treatment efficacy. This study is registered with ClinicalTrials.gov, number NCT04909554. Results: Ninety-nine patients were enrolled from January 2019 to July 2021; 65 received NAC and 34 received NAIC. Baseline characteristics were similar between the two groups. More patients in the NAIC group achieved pCR after surgery than in the NAC group (82.4% vs. 44.6%, p=0.0003). In the NAC group, more patients showed CS (53.8%), and patients with the CS pattern had a significantly higher pCR rate than those with diffuse decrease or no change/enlargement (65.7% vs. 21.7% vs. 14.3%, p=0.0007). In the NAIC group, although a higher proportion of patients showed diffuse decrease (67.6%), all three SP categories had relatively high pCR rates, so pCR was not correlated with SP (85.7% vs. 82.6% vs. 75.0%, p=0.9029). Conclusions: This is the first study to investigate the tumor regression SP of NAIC in TNBC patients. Compared to traditional chemotherapy, NAIC was more prone to diffuse regression, but the relatively high pCR rates had no correlation with the SPs during neoadjuvant therapy. Clinical trial information: NCT04909554 . [Table: see text]
Neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer: A pilot trial.
Authors: Xue Jinqi , Niu Nan , Wang Shuo , Chen Guanglei , Qiu Fang , Zhao Yi , Xing Fei , Zheng Xinyu , Tu Wei , Li Ke , Zhao Hai , Tang Meiyue , Xu Qianshi , Liu Chao , Zhao Yafei , Jiang Xiaofan , Huo Shiwen , Pang Zheng , Zhang Dianlong , Liu Caigang 
Published: June 2023

e12603 Background: Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib plus dalpiciclib (cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with triple-positive breast cancer (TPBC), but the efficacy still needs improvement. This pilot study explored the efficacy and safety of adding trastuzumab to this neoadjuvant regimen in TPBC. Methods: Patients received five 28-day cycles of pyrotinib (320 mg once daily), dalpiciclib (125 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), followed by surgery. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, residual cancer burden (RCB), change in Ki-67 level from baseline to surgery, and safety. Results: Between February 16, 2022 and June 2, 2022, 12 patients were enrolled. Seven (58%; 95% CI, 27.7-84.8) patients achieved tpCR and bpCR. The rate of RCB 0-I was 75% (95% CI, 46.8-91.1%). ORR was 92% (95% CI, 64.6-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5% - 70.5%) at baseline to 17.2% (95% CI, 0.7% - 33.7%) after neoadjuvant therapy (P<0.05). The most common grade 3 adverse events were diarrhea (4 [33%]) and decreased neutrophil count (3 [25%]). No grade 4 events or treatment-related deaths occurred. Conclusions: This four-drug neoadjuvant regimen shows promising pathological response in patients with TPBC, with an acceptable safety profile. The results warranted further validation. Clinical trial information: NCT05228951 .
Neoadjuvant stereotactic body radiotherapy plus dalpiciclib and exemestane for hormone receptor-positive, HER2-negative breast cancer.
Authors: Niu Nan , Cao Shuo , Chen Guanglei , Xue Jinqi , Zhang Yu , Xu Yongqing , Yin Jianqiao , Liu Chao , Jiang Xiaofan , Tang Meiyue , Xu Qianshi , Jia Mingxuan , Zhang Xu , Zhang Zhenyong , Li Huajun , Li Ailin , Liu Caigang 
Published: June 2023

e12604 Background: Despite cyclin dependent kinase 4/6 (CDK4/6) inhibitors having revolutionized treatment for advanced hormone receptor (HR)-positive, HER2-negative (HR+/HER2-) breast cancer, it still has limited efficacy in the neoadjuvant setting. Preclinical studies have indicated radiotherapy followed by CDK4/6 inhibitors can enhance antineoplastic effects. Stereotactic body radiotherapy (SBRT) is more effective than conventional fractionation. This MUKDEN 03 pilot study aimed to explore the efficacy and safety of a chemotherapy-free neoadjuvant regimen with SBRT followed by CDK4/6 inhibitors and endocrine therapy in patients with HR+/HER2- breast cancer. Methods: In this single-center, single-arm prospective study, treatment-naïve patients with unilateral invasive, pathologically confirmed HR+/HER2- breast cancer at stage II-III would be enrolled. Eligible patients received neoadjuvant SBRT (24Gy/3f) to breast target lesion followed by dalpiciclib (150mg daily for 3 weeks on and 1 week off) and exemestane (25mg daily) every 4 weeks for 6 cycles. Patients without menopause also received goserelin 3.6 mg every 4 weeks. The primary endpoint was the proportion of patients with residual cancer burden (RCB) score of 0-I. Key secondary endpoints included objective response rate (ORR), pathologic complete response (pCR), and safety. Results: Between November 2021 and August 2022, 12 enrolled patients completed the study treatment and surgery. The median age was 48.5 years (95% confidence interval [CI], 36-56) and half of them were premenopausal women. 5 (41.7%) patients had stage III disease. The results met the primary endpoint as the therapy resulted in RCB 0-I of 16.7% (2/12, 95% CI 3.5%-46.0%) with the ORR of 91.7% (11/12, 95% CI 62.5%-100%). 2 (16.7%, 95% CI 3.5%-46.0%) patients achieved pCR in the breast and axilla (ypT0/is ypN0). 3 (25.0%, 95% CI 8.3%-53.9%) patients reached pCR in the breast (ypT0/is). The most common grade 3 adverse events (AEs) were neutropenia (8 [66.7%]) and leukopenia (3 [25%]). No patient experienced grade 4-5 AE or death. There was no patient with radiation-related dermatitis and skin hyperpigmentation. Conclusions: Neoadjuvant SBRT followed by dalpiciclib and exemestane seems effective and tolerable, which may offer an alternative for patients with HR+/HER2- breast cancer. The results warranted further validation. Clinical trial information: NCT05132790 .
Efficacy and safety of neoadjuvant double anti-Her2 blockade combined with anthracycline-free chemotherapy in locally advanced breast cancer.
Authors: Rodriguez Garcés Maria Yeray , Samblás Victoria García , Morales Pancorbo David , Bayo Calero Juan Lucas 
Published: June 2023

e12612 Background: Double anti-Her2 blockade combined with chemotherapy (CT) is a standard regimen in Her2 positive locally advanced breast cancer (LABC) with a high risk of relapse. TCHP provides more anti-Her2 treatment, better pathological complete response (pCR) rates and less cardiotoxicity. However, it is not a very widespread option due to the risk of toxicity. Our group shows a manageable toxicity profile by adding G-CSF as primary prohylaxis. Methods: We describe our experience with neoadjuvant TCHP and pegfilgrastim combination between years 2017-2023. Efficacy and safety were analyzed and compared with other schemes accepted by clinical guidelines. Results: 62 patients, median age 48 years; 61.3% were premenopausal; 54.8% were stage II at diagnosis and 45.2% were stage III; 67.7% had N+; 62.9% had RH-. A total of six cycles were completed in 85.5%; 8 patients discontinued treatment due to toxicity. The most frequent adverse events were hematological (grade 3-4 in 8.1%) and digestive (grade 3-4 in 19.4%). No cardiac event was reported. 6.5% were hospitalized due to toxicity (3.2% febrile neutropenia). Dose reduction was needed in 43.5%. Clinical response occurred in 98.4% and radiological response in 87.1% (complete in 38.7%). pCR (ypT0/isN0) was obtained in 67.7% (66.7% in N+; 77.4% in RH-). Up to now, 4 patients have relapsed (3 of them had pRC) and 3 have died. After median 24.5 months of follow-up, the median relapse-free and overall survival by Kapplan-Meier have not been reached. Cox regression shows that getting rPC does not impact survival. The Odds Ratio shows a higher proportion of obtaining pRC in the RH- and N+ subgroups, but without statistically significant differences. Conclusions: Our data based on combination of TCHP and pegfilgrastim shows considerable efficacy with an acceptable toxicity profile. The main advantage is the intensification of double lock dose, without anti Her2 window period, avoiding the addition of anthracyclines and, therefore, cardiac toxicity. pRC and toxicity profile results were better than other regimen proposed in other studies. Our data shows that pRC has no impact on survival. We assume a favorable association between pRC and N+ and HR-, although not statistically significant, probably due to the small amount of patients. Based on these favorable results, we believe that the priority use of TCHP-GCSF should be considered in the neoadjuvant treatment of Her2+ LABC. [Table: see text]
Neoadjuvant tucidinostat combined with chemotherapy for hormone receptor-positive, HER2-negative breast cancer.
Authors: Niu Nan , Xue Jinqi , Qiu Fang , Chen Guanglei , Gu Xi , He Guijin , Cao Shuo , Yu Xiaopeng , Xu Yongqing , Yin Jianqiao , Han Sijia , Han Ye , Tang Meiyue , Zhao Yafei , Zheng Ran , Zheng Xinyu , Xu Hong , Liu Caigang 
Published: June 2023

e12617 Background: Both neoadjuvant chemotherapy and endocrine therapy only result in trivial pathological complete response rates and moderate objective response rate (ORR) in hormone receptor (HR)-positive, HER2-negative breast cancer, more promising alternatives are urgently needed. Tucidinostat is an oral subtype-selective histone deacetylase inhibitor that has shown efficacy and safety when used in combination with exemestane in patients with advanced HR+ breast cancer. This MUKDEN 05 study aimed to assess the efficacy and toxicity of the combination of tucidinostat and EC-T as a neoadjuvant strategy in patients with HR+/HER2-, stage II-III breast cancer. Methods: This study is a multicenter, single-arm, phase II study. Eligible patients received 20 mg tucidinostat orally twice a week (on days 1, 4, 8, and 11), 2 weeks on, 1 week off. The dose and administration schedule of EC-T were as follows: 4 cycles of epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100 mg/m2 every 3 weeks. The primary endpoint was the proportion of residual cancer burden (RCB) 0-I. Key secondary endpoints included pathological complete response (pCR), objective response rate (ORR), and safety. Results: Between May 2022 and August 2022, a total of 35 patients were enrolled. 27 patients were pathologically evaluable. The remaining 8 patients have completed neoadjuvant treatment and wait for operation. The ratio of RCB 0-I was 37% (95% CI, 23.2-53.7%). ORR was 86% (95% CI, 70.6-93.7%). Four (15%; 95% CI, 5.91-32.5%) patients achieved bpCR, and one (4%; 95% CI, 0.67-18.3%) patients achieved tpCR. Most adverse events (AEs) were grade 1 or 2. Grade 3/4 AEs included neutropenia (21.1%), and thrombocytopenia (15.8%). Conclusions: The combination of Tucidinostat and EC-T had an acceptable safety profile and encouraging clinical responses, offering a neoadjuvant treatment option for patients with early HR+/HER2- breast cancer. Further research is required to validate these findings. Clinical trial information: NCT05400993 .
Comparing time to treatment for neoadjuvant chemotherapy for breast cancer across the urban-rural continuum.
Authors: Kasper Laura , Coogan Alison , Akers Rachel , Lunt Lilia , Madrigrano Andrea , Dixon Matthew , O'Donoghue Cristina 
Published: June 2023

e12619 Background: Time-to-treatment is a quality measure in breast cancer care that can impact breast cancer survival as delayed treatment can increase mortality. This study aims to determine whether differences exist in time-to-treatment for breast cancer patients receiving neoadjuvant chemotherapy (NAC) across the urban-rural continuum. Methods: The National Cancer Database (NCDB) was queried for women with a diagnosis of breast cancer between 1 January 2004 – 31 December 2019. Patients who fit criteria for NAC consideration according to NCCN guidelines were included (inflammatory breast cancer, HER2 positive with tumor stage >T1c, triple negative with tumor stage >T1c, HER2 positive or triple negative lymph node positive, and stage III estrogen receptor (ER) positive). Analysis was stratified according to histopathologic subtype and geographic location as defined by the NCDB. Differences were analyzed using χ2 tests. Results: For patients with NAC-eligible breast cancer, there was no statistically significant difference in terms of days until treatment for each histopathologic subtype across the urban-rural continuum. The distance to treatment facility increases the further away patients are from a large metropolitan area, with individuals located in an urban area that is not adjacent to a metro area traveling the furthest distance (12.7mi large metro, 18.1mi small metro, 36.7mi urban adjacent to metro, 62.6mi urban not adjacent to metro, 56.4mi rural). No significant difference in distance traveled was observed between tumor subtype group. Conclusions: While previous studies have determined that rural patients receive NAC at lower rates than those in large urban areas, this study shows that time to treatment and distance traveled is similar across rural urban continuum and different histopathologic subtypes. Future studies are needed to determine why patients receive NAC at lower rates in rural areas.
Analysis of pathological complete response (PCR) and impact of modifiable risk factors on the premature discontinuation of pertuzumab use in early stage HER-2 breast cancer: A retrospective single-institutional study.
Authors: Anwar Khurram , Khatri Jai Kumar , Masoudi Mohd , Abdallah Mahmoud , Tahboub Ihab , Nwanwene Kemnasom , Howide Eldib , Tria Tirona Maria Rosalia 
Published: June 2023

e12627 Background: In patients with HER-2 positive breast cancer, Pertuzumab in combination with Trastuzumab forms a potent Anti HER-2 regimen. Randomized clinical trials have concluded that addition of Pertuzumab to Trastuzumab and Chemotherapy leads to improved rates of Pathological Complete Response and also improved Invasive-disease-free survival rates in early stage HER-2 positive breast cancer. Pertuzumab is frequently associated with treatment limiting diarrhea and other adverse effects. In this study, we report our experience with the use of Pertuzumab in early stage HER-2 breast cancer. We analyzed the adverse events, PCR rates for those patients who had premature discontinuation of treatment versus those who had successful treatment completion, and modifiable risk factors that may have affected completion of treatment. Methods: We conducted an IRB approved, retrospective study, analyzing the use of Pertuzumab at our institution for early stage (Stage I-III), HER-2 positive female and male breast cancer patients seen from June 2018 to June 2022. Data were obtained from our Institutional Cancer Registry. Results: One hundred and eighteen (118) patient charts were reviewed. Sixty Five (55.08%) patients received Pertuzumab. Of the patients who received Pertuzumab, 61 (93.85%) received it in the Neoadjuvant setting. Thirty Eight (58.46%) patients completed the treatment and 27 (41.5%) patients had premature treatment discontinuation due to adverse effects. The rate of PCR in patient who completed the prescribed treatment course was 55.56%, and 51.85% for those who did not (p value 0.77). Among the patients in whom treatment was discontinued, diarrhea (51%), followed by rash (11.11%) were the main adverse effects. Almost 66% of non-smokers completed treatment as compared to 48% of smokers (p value 0.15). Patients with a normal BMI had a treatment completion rate of 76% compared to obese or overweight patients who had a rate of 52% (p value 0.08). Conclusions: Our retrospective study showed that there was a high premature discontinuation rate of the use of Pertuzumab. This is due to adverse effects, diarrhea being the most notable. However, the PCR rate difference was not statistically significant (55.56 vs 51.85, P value 0.77) in patients who completed treatment versus those who did not. There was a positive trend observed that non-smokers and non-obese patients were more likely to complete treatment with Pertuzumab. Although it was observed that premature discontinuation of Pertuzumab did not significantly impact PCR, further studies are required to validate this observation.
Serial multiomic analysis in advanced breast cancer: A novel platform to inform therapeutic decisions.
Authors: Kong Ben , Keck Jamie , Johnson Brett , Stommel Jayne , Zheng Christina , Siex Kiara , Guimaraes Alexander , Corless Christopher L. , Mitri Zahi Ibrahim , Gray Joe W. , Mills Gordon B. , Bergan Raymond C. ,   SMMART Clinical Trials Program
Published: June 2023

e13001 Background: We designed and implemented a platform wherein patients with metastatic treatment-refractory cancer would receive individually tailored treatment informed by multi-omic data and iteratively adapted in real-time. Here we describe the workflow of this platform and quantify operational characteristics for a metastatic breast cancer cohort. Methods: Participants with metastatic breast cancer progressing after standard-of-care therapy were enrolled. Sites demonstrating disease progression were targeted for biopsy. Resultant tissue was analyzed by a next-generation sequencing (NGS) solid tumor panel, whole exome sequencing, whole transcriptomic sequencing, multiplex protein analysis of a panel of cancer-relevant proteins and phosphoproteins, and focused immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) analysis. Results: Between 1/1/2017 to 12/31/2021, 74 participants were consented and 55 were enrolled. Median age at enrollment was 54 years, most were ECOG 0-1, and received a median of 2 lines of therapy in the metastatic setting. There were 95 biopsies collected from 55 individual participants and analytics were successfully generated in 94% of the cases. At the provider’s request, an integrated clinical, molecular, and cancer biology tumor board (TB) was convened for 25 participants. A total of 21 participants received matched therapy based on clinical parameters coupled to a consideration of biologically informed therapeutic vulnerabilities and 6 had a PFS2/PFS1 > 1.3. Twenty-one participants had a median of 2 repeat progression biopsies (range 2-5) and new alterations with potential therapeutic implications were identified. Repeat biopsies could have led to a new treatment in 11 of the participants, though only 3 received a therapy recommended by the tumor board owing to either rapid disease progression, clinical deterioration, or lack of access to drug. Conclusions: We demonstrated the practical feasibility and initial operating characteristics of a platform designed to comprehensively understand and integrate the clinical and molecular characteristics of a cohort with metastatic progressive breast cancer as they evolve on therapy and to use this information to deliver iteratively tailored therapy in real time. Further, clinical responses were observed in a subset of participants. These findings suggest an opportunity to incorporate this platform earlier in a disease course or to design adaptive clinical trials with access to therapies aimed at targeting new biological alteration.