bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncologic outcomes for different axillary staging techniques in nodal positive breast cancer undergoing neoadjuvant systematic treatment: A cancer registry study.
Authors: Pfob André , Kokh Daria , Surovtsova Irina , Riedel Fabian , Heil Joerg , Morakis Philipp ,   KRBW (Krebsregister Baden-Württemberg)
Published: June 2023

e12571 Background: The optimal axillary staging technique for patients with nodal positive breast cancer undergoing neoadjuvant systemic treatment (NAST) is unclear. Less invasive, targeted approaches like targeted axillary dissection (TAD) or sentinel-lymph node biopsy (SLNB) recently showed false-negative rates < 10% compared to axillary lymph node dissection (ALND). Oncologic outcomes, however, are unknown. Methods: We identified nodal positive breast cancer patients undergoing NAST from 2016 to 2021 with at least 1-year follow-up and available information regarding axillary staging from the state cancer registry of Baden-Wuerttemberg, Germany. Invasive disease-free survival (iDFS) was assessed using Kaplan-Meier statistics and multivariate cox regression models (adjusted for age, pN stage, pT stage, and tumor biologic subtype). Results: A total of 2403 patients with a median follow-up of 23.2-months after surgery were identified: 1963 underwent ALND, 407 underwent SLNB (in 230 cases, three or more sentinel nodes (SLNs) were removed and in 177 cases, 1-2 SLNs were removed), and 33 underwent TAD. The proportion of patients with pN+ stage within these four groups was 54%, 31%, 26%, and 35%, respectively ( P < 0.001). Significant differences in iDFS between the ALND, SLNB, and TAD groups were observed (log rank P = 0.046): iDFS 2 years after surgery was 74.5% (ALND), 80.2% (SLNB ≥3 removed SLNs), 85.6% (SLNB < 3 removed SLNs), and 88.4% (TAD), respectively. iDFS after 4 years was 61.5% (ALND), 69.1% (SLNB ≥3 removed SLNs), and 74.6% (SLNB < 3 removed SLNs), respectively. Multivariate cox regression analysis showed no significant influence of different axillary staging techniques on iDFS: HR 0.91 (95% CI 0.55 to 1.52) for SLNB with ≥3 removed SLNs, HR 0.99 (95% CI 0.59 to 1.67) for SLNB with < 3 removed SLNs (reference = ALND). Conclusions: This data suggests that ALND provides no benefit in terms of iDFS compared to targeted approaches like TAD or SLNB for patients with nodal positive breast cancer undergoing NAST. Future studies with longer-term follow-up are welcomed to fully inform this discussion.
Impact of distance between tumor and nipple on survival outcomes in breast cancer.
Authors: Cheun Jong-Ho , Kang Eunhye , Chun Jung Whan , Kim Hong-Kyu , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik , Hwang Ki-Tae 
Published: June 2023

e12579 Background: Mastectomy is usually recommended surgical procedure for centrally located tumors regarding the increased risk of nipple invasion. Despite no difference in survival outcomes based on tumor locations, central tumor may have a higher chance of main lactiferous duct invasion, leading to tumor cell can migration to periphery of the breast. In this study, we investigated the relationship between locoregional recurrence (LRR) and the tumor-to-nipple distance (TND). Methods: We retrospectively analyzed the data of patients who underwent breast cancer surgery between 2004 and 2018 at two institutions. Patients who underwent neoadjuvant chemotherapy were excluded. TND was measured using preoperative MRI records. Results: A total of 9,014 patients were included, and median TND was 3.4 (0.0-15.0)cm. A restricted cubic spline curve showed that the hazard risk of LRR increased with shorter TND for all patients. While the risk of LRR appeared to apparently increase in the breast-conserving surgery (BCS) group, the mastectomy group showed the constant pattern. Thus, we conducted survival analysis for 5,455 patients who underwent BCS. We set the TND cutoff at 2.5 cm, which showed the lowest p-value for LRR rate. Compared to those with TND > 2.5cm, patients with TND≤2.5cm had significantly lower rates of LRR (HR,1.83; 95%CI,[1.37-2.46], p < 0.001) and distant metastasis (DM) (HR,1.53; 95%CI,[1.16-2.02], p = 0.002). However, overall survival was not different between the two groups (p = 0.405). Cox-regression analysis showed that TND still had a significant impact on LRR (HR,1.52; 95%CI,[1.11-2.09], p = 0.010) but not on DM. Importantly, TND still remained significant factor affecting LRR when analyzed as continuous variable (HR,1.04; 95%CI,[1.02-1.06], p < 0.001). The prognostic impact of shorter TND was more evident in patients with high mammographic density. Conclusions: BCS can be considered a safe option for central tumors, but mastectomy could be a better choice for patients who are concerned about recurrence or unwilling to undergo additional surgeries.
A meta-analysis of cardiac toxicity of concurrent epirubicin and trastuzumab in early breast cancer.
Authors: Yang Minghan , Huang Chiun-Sheng , Chang Dwan-Ying , Chen I-Chun , Lin Ching-Hung , Lu Yen-Shen 
Published: June 2023

e12583 Background: The concurrent use of doxorubicin and trastuzumab has been limited due to the increased risk of cardiac toxicity. Epirubicin is a less cardiotoxic alternative to doxorubicin, and the change in ejection fraction occurs until its cumulative dose doubles that with doxorubicin. This study aims to evaluate the cardiotoxicity and pathological complete response (pCR) rate associated with concurrent usage of epirubicin and trastuzumab in patients with HER2 positive early breast cancers (EBC). Methods: A literature search was conducted on NCBI/PubMed, and Cochrane database for phase II or III randomized controlled trials of concurrent use of epirubicin and trastuzumab in HER2 positive EBC between January 1, 2000 and February 28, 2021.The definition of adverse cardiac events varied among these trials, including changes in left ventricular systolic function and clinical heart failure. To compare the risk of cardiotoxicity and the odds of pCR rate between concurrent and non-concurrent regimens, a meta-regression analysis utilizing fixed-effects and mixed-effects linear models was conducted to investigate the relationship between various covariates. Results: Seven trials containing concurrent use of epirubicin and trastuzumab involving 1797 patients were analyzed. All of them are neoadjuvant studies. The median cumulative dose of epirubicin used was 300mg/m2 and there were a total of 96 reported cardiac adverse events. The concurrent use of epirubicin and trastuzumab did not result in a statistically significant increase in cardiotoxicity compared to non-concurrent regimens (risk ratio = 1.18, 95% CI: 0.68-2.05). Meanwhile, there was a significant increase in pCR rate with the concurrent regimens (odds ratio = 1.48, 95% CI: 1.04-2.12). Mixed-effects meta-regression analysis showed that in trials with higher proportion of hormone receptor-positive EBC patients, the risk ratio of cardiotoxicity significantly increased with concurrent regimens and pathological complete response rate became less significant. Conclusions: The concurrent use of a limited dose of epirubicin and trastuzumab demonstrated a positive impact on pCR rate without a significant increase in cardiotoxicity. Further research is necessary to fully comprehend the long-term safety profile in individuals with metastatic breast cancer. [Table: see text]
Association of circulating tumor DNA with survival in neoadjuvant-treated triple negative breast cancer independent of pathological complete response.
Authors: Li Yan , Chen Xiaobin , Lin Yuxiang , Fu Fangmeng , Wang Chuan 
Published: June 2023

e12588 Background: Many patients with triple negative breast cancer (TNBC) still succumb to their disease after systematic treatment. It is crucial to identify those at high risk. Circulating tumor DNA (ctDNA) has recently become a promising marker to monitor tumor burden. Our study aimed to evaluate the clinical value of the presence and dynamic change of ctDNA to predict the tumor response and prognosis in TNBC patients treated with neoadjuvant chemotherapy (NAC). Methods: Cell-free DNA (cfDNA) was isolated from pre-NAC plasma samples and then analyzed by duplex sequencing. A Chi-square test or Fisher exact test were used for categorical variables. Kaplan‐Meier analysis with a Log‐rank test and the Cox proportional hazard regression model were used for the univariate and multivariable survival analysis. Survival prediction was assessed using a time-dependent receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Results: A total of 82 TNBC patients receiving NAC were enrolled. Baseline ctDNA detection indicated significantly worse survival. TP53 and genes involved in PI3K-Akt signaling pathway mutations were significantly associated with survival independent of the pathological complete response (pCR). A TP53 detection combined clinical model is highly predictive, with a time-dependent ROC of 0.936 for 3-year overall survival (OS), compared to the model including clinical variables only (AUC of the clinical predictor: 0.751, P= 0.028). Conclusions: Baseline ctDNA detection, TP53 mutations, and genes involved in PI3K-Akt signaling pathway mutation are all independent prognostic factors in TNBC patients receiving NAC. A TP53 detection combining model is highly predictive.
Real-world, single-center experience on the outcomes of neoadjuvant chemotherapy and trastuzumab alone or in combination with pertuzumab in human epidermal growth factor receptor-2 breast cancer patients.
Authors: Vaid Ashok Kumar , Sharma Devender , Wadhwa Jyoti , Agarwal Rajeev Kumar , Kaur Kanchan , Goyal Shina , Gautam Dheeraj , Arora Jyoti , Gupta Sabhyata , Goel Ruchika , Sen Ashok 
Published: June 2023

e12589 Background: Neoadjuvant chemotherapy (NACT) is the standard of care for early-stage breast cancer (BC). Human epidermal growth factor receptor 2 (HER2) positive disease constitutes a large proportion of BC patients, and HER2 overexpression is associated with poor prognosis. The introduction of HER2+ targeted therapies, such as trastuzumab and pertuzumab, has resulted in improved outcomes in HER2+ BC. NACT in combination with HER2 targeted therapies aims at achieving pathological complete response (pCR) and an improved survival rates. Methods: We performed a retrospective review of HER2+ BC patients who were treated at Medanta – The Medicity Hospital, Gurugram, Haryana, India, between 2011 and 2021. A total of 108 HER2+ BC patients who received NACT with platinum, anthracycline or taxane-based regimens, along with trastuzumab alone or in combination with pertuzumab, were included. Results: Of 108 enrolled patients, 66 and 42 patients received neoadjuvant single-blockade (trastuzumab) and dual-blockade (trastuzumab and pertuzumab) anti-HER2 therapy, respectively. The majority of patients were aged < 60 years. The patient populations were comparable in terms of clinical stage, hormone receptor status, histopathology category [Invasive ductal carcinoma (IDC) being most common] and Ki67 status for both groups. All patients had IHC3+/FISH+ HER2 expression. No significant (p = 0.896) difference was observed for breast conserving surgery between the groups. A higher pCR rate after surgery was reported in the dual-blockade versus single-blockade group (50% vs. 39.2%; p = 0.271). The median follow-up duration was 21.9 and 15.2 months in the single-blockade and dual-blockade groups, respectively. For dual- vs. single- blockade groups, the 1-year OS rates were 100% each, and 3-year OS rates were 100% vs. 98.48%. For dual- vs. single- blockade groups, the 1-year DFS rates were 100% vs. 95.45%, and 3-year DFS rates were 92.85% vs. 80.3% respectively. Conclusions: Neoadjuvant chemotherapy with dual HER2-blockade had higher pCR and survival rates compared with the single HER2-blockade strategy in HER2 positive breast cancer. [Table: see text]
Factors associated with response to neoadjuvant chemotherapy and immune checkpoint inhibition in triple-negative breast cancer.
Authors: LeVee Alexis , Wong Megan , Flores Sarah , Ruel Nora H. , Lavasani Sayeh Moazami , Patel Niki , Sedrak Mina S. , Stewart Daphne B. , Waisman James Ross , Yuan Yuan , Mortimer Joanne E. 
Published: June 2023

e12593 Background: Immune checkpoint inhibition with pembrolizumab plus neoadjuvant chemotherapy is now the standard-of-care in patients with high-risk triple-negative breast cancer (TNBC) based on the KEYNOTE-522 trial. The trial demonstrated that the addition of pembrolizumab improves pCR, but it is currently unclear which patients benefit most from the addition of immunotherapy (IO). We sought to identify which demographic and clinical characteristics were associated with response to neoadjuvant pembrolizumab plus chemotherapy. Methods: We performed a single institution, retrospective study of early-stage TNBC patients treated with neoadjuvant chemotherapy and pembrolizumab between March 1st, 2020 and December 1st, 2022. We excluded patients who had not undergone definitive surgery. We collected demographic information, clinical and pathologic characteristics, and treatment data. Pathologic complete response (pCR) was defined by ypT0/Tis and ypN0. Multivariate analysis was performed using logistic regression to identify factors associated with pCR. This study was approved by the City of Hope Institutional Review Board. Results: 67 patients were analyzed with a median age of 56 years and median BMI of 29. Self-reported racial groups included 25 Hispanic patients (37%), 23 non-Hispanic White (34%), 9 Asian (13%), 6 Black (9%), and 4 other/unknown (6%). 6 (9%) patients were BRCA1+ and 1 (1.5%) patient was BRCA2+. The majority of patients had invasive ductal carcinomas (91%), were clinical T2 stage (65.7%), and node negative (52.2%). The median number of cycles of neoadjuvant IO was 7 (IQR 4-8) and median months from start of IO to surgery was 6 (IQR 4.6-6.7). 42 (62.7%) patients had a pCR. Multivariate results showed that patients under 50 years at time of diagnosis (vs. age > 50 years), those with grade 3 (vs. 2), and those receiving 7 or more cycles of pembrolizumab (vs. < 7) had improved rates of pCR (ORs 5.7, 8.1, and 3.4, respectively, p < 0.05). BMI, race, BRCA1/2 status, histopathology, clinical T and N stage, and timing of start and end of IO to surgery were not significantly associated with pCR. Conclusions: Younger TNBC patients with high tumor grade were more likely to respond to treatment with neoadjuvant pembrolizumab and chemotherapy. More cycles of treatment with pembrolizumab was also associated with response. Further research to identify which patients with TNBC benefit from the addition of pembrolizumab to chemotherapy is necessary to determine whether its additional toxicity and cost are warranted.
Phase II neoadjuvant trial of albumin-bound paclitaxel, trastuzumab and pertuzumab followed by anthracycline based regimens in patients with operable HER2 positive breast cancer (OMC-BC05).
Authors: Iwamoto Mitsuhiko , Ikari Ayana , Tominaga Tomo , Maezawa Saki , Sakane Junna , Oku Hiroyo , Yoshidome Katsuhide , Morimoto Takashi , Fujioka Hiroya , Hagihara Seita , Nitta Toshikatsu , Matsutani Ayumi , Kimura Kosei 
Published: June 2023

e12594 Background: Anthracycline and Taxane have been widely used and studied in neoadjuvant setting for treatment of locally advanced breast cancer. Various regimens have explored the addition of newer agents to determine safety and efficacy, and pathological complete response(pCR) has been demonstrated to be associated with favorable overall survival in primary breast cancer. Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to Trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (Her2)-positive breast cancer. In addition, APHINITY trial showed that Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to Tastuzumab and chemotherapy. We conducted a clinical phase II neoadjuvant trial of nab-Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline Based Regimens in Patients with Operable Her2 Positive Breast Cancer. Methods: The study is designed to evaluate nab-paclitaxel, Trastuzumab and Pertuzumab followed by EC or AC or FEC as neoadjuvant therapy in patients with Her2 positive operable breast cancer. Patients are treated with neoadjuvant nab-paclitaxel(260 mg/m2 ), Trastuzumab and Pertuzumab followed by EC(Epirubicin 90 mg/m2 , Cyclophosphamide 600 mg/m2) or AC(Doxorubicin 60 mg/m2 , Cyclophosphamide 600 mg/m2) or FEC(Fluorouracil 500mg/m2, Epirubicin 100 mg/m2 , Cyclophosphamide 500 mg/m2 ) q21d x 4. Patients undergo surgery 4-6 weeks later from completing chemotherapy. The primary endpoint, pCR is defined as no evidence of invasive tumors in the final surgical sample both in the breast and axillary lymph nodes. Secondary endpoints include overall response rate, disease-free survival, rate of breast conserving surgery, histological response rate, rate of sensory neuropathy ant the safety of the treatment. Results: In 30 evaluable patients, the pCR rate was 50%; 6/19 (31.6%) in ER-positive and 9/11 (81.8%) in ER-negative, 1/7 (14.3%) in IHC 2+, FISH positive and 14/23 (60.9%) in IHC 3+ . Of the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; no patient required a dose reduction for nab-PTX because of peripheral neuropathy. Conclusions: Neoadjuvant treatment using albumin-bound Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline based regimens appears to be effective especially in pure HER2 type or IHC 3+ cases.
Informative tools to optimize neoadjuvant therapy in ER positive, HER2 negative breast cancers.
Authors: Luzhna Lidiya , Chia Stephen , Pauls Mehrnoosh , LeVasseur Nathalie 
Published: June 2023

e12595 Background: Neoadjuvant therapy (NAT) in HR+/HER2- tumors is often disputable. While the role of Oncotype DX has been well established in adjuvant settings, its clinical utility and potential implementation for prediction of NAT benefit requires further study. This ongoing study aims to report the feasibility of Oncotype DX testing on core biopsy specimens prior to NAT in patients with operable HR+/HER2- breast cancer. The effect of the recurrence score (RS) on systemic treatment recommendations and its correlation to dynamic markers of proliferation and NAT response will be evaluated. Methods: Participants with clinical T2-T4 and/or node positive HR+/HER2- breast cancer had Oncotype DX testing done prior to NAT. Clinico-pathological information, treatment regimens, clinical, radiologic, and pathological responses were recorded. Results: Of the 48 patients with HR+/HER2- breast cancer referred to BC Cancer Vancouver for consideration of NAT between September 2021 and January 2023, 26 were eligible and enrolled in the study. The success rate of the Oncotype DX on core biopsy samples was 96%. The mean turnaround time from patient consent to RS report was 19 calendar days. Approximately 32% of tumors had a RS equal or higher than 26 while 4% had a score less than 10. Nearly 25% of neoadjuvant treatment recommendations were changed based on the RS. Overall, 33% of patients received neoadjuvant chemotherapy, 54% received neoadjuvant endocrine treatment, and 12.5% proceeded with upfront surgery. Conclusions: The success rate of Oncotype DX testing on core biopsy samples was excellent. There were multiple factors that influenced trial enrollment, highlighting the low uptake and equipoise of NAT use in HR+/HER2- tumors. The Oncotype DX testing resulted in a change in systemic treatment plan in 25% of patients. Analyses are ongoing to correlate the recurrence score to NAT response, dynamic Ki-67 changes and breast MRI changes. Clinical trial information: NCT03790813 .
The impact of exercise training on the pathologic response and tumor immune microenvironment in breast cancer after neoadjuvant chemotherapy: An exploratory study.
Authors: Guedes Helena , João David , Antunes Pedro , Silva Sandra , Leão Inês , Esteves Dulce , Helguero Luisa , Costa Telma , Viamonte Sofia , Alves Alberto , Caldas Margarida , Joaquim Ana 
Published: June 2023

e12596 Background: In early breast cancer (BC), pathological complete response (pCR) is an efficacy endpoint of neoadjuvant chemotherapy (ChT) and percentage of tumor-infiltrating lymphocytes (TILs) is a prognostic biomarker. Although exercise training is an evidence-based supportive care across the BC journey, one open question is its impact on the antitumor effect of neoadjuvant ChT. The authors aim to investigate the effects of a supervised exercise training program (STEP) in pCR and TILs in BC women undergoing neoadjuvant ChT. Methods: MAMA_MOVE_Gaia on Treatment (ISRCTN, ISRCTN32617901) is randomized controlled trial in which women with early BC undergoing anthracycline containing ChT were randomized in a 1:1 ratio to a SETP or to usual care, close to recruitment in January 2022. For this exploratory analysis, we retrospectively identified patients who underwent neoadjuvant ChT, and compare pCR and TILs between the two arms. Results: Sixty-four participants were included, aged from 26 to 72 years old (mean = 50.3, SD = 10.1) majority with stage II and III (n = 58, 90,6%) and HER2+ (n = 23, 35.9%) or triple negative (n = 19, 29.7%) disease. The pCR in STEP arm had a prevalence of 56.7% and in the usual care arm of 55.9%(p = 0.950). In the STEP arm median TILs were, for the biopsy and tumor site, of 5.0 (range 0.0-80.0) and 5.0 (range 5.0-30.0). In the usual care arm, median TILs were, for the biopsy and tumor site, of 5.0 (range 0.0-90.0) and 0.0 (range 0.0-30.0). There was no difference between groups for TILs of the biopsy (p = 0.907). Higher TILs of the tumor site was marginally associated with the STEP arm (p = 0.082). Conclusions: Despite the results obtained, it is believed that a larger sample may lead to different results. However, these data could also support future research in this field, bringing new insights for cancer survivors continuum of care.