bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mastectomy and immediate prepectoral versus submuscular breast reconstruction after neoadjuvant chemotherapy: Our early experience.
Authors: Scardina Lorenzo , Moschella Francesca , Magno Stefano , Sanchez Alejandro Martin , Di Leone Alba , D'Archi Sabatino , Franco Antonio , Biondi Ersilia , Carnassale Beatrice , Di Micco Annalisa , Bria Emilio , Masetti Riccardo , Franceschini Gianluca 
Published: June 2022

e12618 Background: Conservative mastectomy with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that allows to improve aesthetic results and patient quality of life. Traditionally, implants have been placed in a submuscolar (SM) plane beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of prosthesis is increasingly used in order to avoid morbidities related to manipulation of PMM. The aim of this study was to compare outcomes of SM vs PP IPBR after conservative mastectomy in patients with histologically proven breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: In this retrospective observational study we analyzed two cohorts of patients that underwent mastectomy with IPBR after NAC in our Istitution from January 2018 to December 2021. Conservative mastectomy was performed in 155 of the 400 patients that underwent NAC during the study period. Patients were divided in 2 groups based on the positioning of implants: 60 SM versus 95 PP. Results: The two cohorts were similar for age (mean age 45 and 42 years in the SM and PP group respectively) and follow‐up (32 and 21 months, respectively). Mean operative time was 55 minutes shorter in the PP group (298 and 243 minutes in the SM and PP group). No significant differences were observed in overall major complication rates. Implant loss occurred was observed in 1.6% of patients (1/60) in the SM group and 1,05% of patients (1/95) in PP group. No differences were observed among the two groups in local or regional recurrence. Conclusions: Our preliminary experience, that represents one of the largest series of PP-IPBR after NAC at a single Institution documented in the Literature, seems to confirm that PP - IPBR after NAC is a safe, reliable and effective alternative to traditional SM - IPBR with excellent aesthetic and oncological outcomes; it is easy to perfom, reduces operative time and minimizes complications related to manipolation of PPM. However this promising results need to be confirmed in prospective trials with longer follow-up.
Neoadjuvant pegylated liposomal doxorubicin (PLD) plus cyclophosphamide followed by nab-paclitaxel (Nab-P) as primary chemotherapy continuously combined with dual HER2 blockage for HER2-positive breast cancer: A single-arm phase 2 trial (Brecan Trial).
Authors: Yang Jixin , Yang Yuqing , Wen Xinxin , Wu Jiang , Yu Jing , Wang Lei , Huang Meiling , Hu Wenyu , Ma Wen , Li Nanlin 
Published: June 2022

e12622 Background: Despite that AC-THP regimen is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that pCR rate rarely exceeds 70%. We hypothesized that prolonged dual anti-HER2 therapy can increase pCR rate in neoadjuvant therapy. In this study, we designed a single-arm trial of ACHP-THP regimen (continuous dual anti-HER2 therapy of trastuzumab and pertuzumab) in neoadjuvant therapy of HER2 positive breast cancer. To minimize adverse cardiovascular events, we used pegylated liposomal doxorubicin (PLD) and Nab-Paclitaxel (Nab-P) instead of doxorubicin and paclitaxel. We aimed to examine whether continuous dual anti-HER2 therapy can boost pCR rate in the neoadjuvant therapy. The cardiotoxicity was closely monitored when the anti-HER2 therapy was combined with PLD and Nab-P respectively. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy, were enrolled. The patients were treated with PldCHP (pegylated liposomal doxorubicin 35mg/m2, cyclophosphamide 600mg/m2, trastuzumab 8 mg/kg loading, then 6 mg/kg, pertuzumab 840 mg loading, then 420 mg, iv, q3w) for 4 cycles followed by Nab-PHP (Nab-Paclitaxel 260mg/m2, trastuzumab 6 mg/kg, pertuzumab 420 mg, iv, q3w) for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity during neoadjuvant therapy. Results: From January 2020 to October 2021, a total of 96 patients were recruited. Among the 96 patients with a median age of 49 (21-71), 58 patients were HR positive and 42 patients had positive lymph node status. Overall, the pCR rate was 80.2% (77/96). The ER-positive tumor achieved a higher pCR rate than ER-negative tumor (82.8% vs 76.3%, p=0.439), but the difference was statistically insignificant. Multivariate regression analysis showed that for participants older than 30, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were neutropenia (30.2%), asthenia (8.3%), and peripheral sensory neuropathy (7.3%). Left ventricular insufficiency was detected in 4 patients, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusions: The PldCHP---Nab-PHP regimen is a feasible and effective neoadjuvant therapy for early stage HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for continuous dual anti-HER2 therapy combined with PLD in neoadjuvant or adjuvant therapy of HER2 positive breast cancer.
A novel patient-derived organoid model for triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy for screening personalized drugs.
Authors: Liu Feiyang , Ma Dandan , Liu Qingsong , Qi Xiaowei 
Published: June 2022

e12625 Background: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence. In this study, we developed a novel organoid culture method for growing TNBC patient samples after NAC, with the goal of generating models that more faithfully recapitulates the key features of the primary tumor for screening personalized drugs. Methods: We established organoid lines derived from TNBC patients who had residual tumors after anthracycline and taxane±platinum based NAC as well as normal human mammary tissues. The histopathology signatures of organoid lines were characterized by H&E staining and immunohistochemistry. The genetic and transcriptional features of organoids were analyzed by targeted sequencing and RNA sequencing. A set of clinical drugs were screened for their ability to suppress cancer organoids in vitro and the consistency was also analyzed between clinical response and drug efficacy of organoid models. Results: A total of 10 cancer organoid lines were successfully established, and cultured stably for more than 4 months. For comparison, 2 organoids derived from normal mammary tissues were generated as well. Our success rate for establishing cancer organoids from TNBC patient samples after NAC was 83% (10 out of 12 samples), and for organoids from normal mammary tissues, it was 100% (2 out of 2 samples). These organoid lines closely recapitulated the histopathology, genetic and transcriptional signature, and intratumor heterogeneity of the primary tissues. We found that active PI3K/AKT/mTOR pathways signaling is always required for cancer organoids from TNBC patient samples after NAC, while Wnt pathway activation is dispensable for generation of them in comparison to the organoid cultures from normal breast tissues. More importantly, we found that the anti-Trop-2 antibody-drug conjugate sacituzumab govitecan (IMMU-132) showed higher sensitivity to most cancer organoids from TNBC patient samples after NAC (8 out of 10 samples) with IC50 ranging from 0.3 nM to 86 nM in contrast to 5-FU (5 out of 10 samples) with IC50 ranging from 0.9 μM to 10.2 μM in vitro, whose prodrug capetabine is considered as a standard option in the postneoadjuvant setting. These results were also confirmed in patient-derived tumor xenograft models. The consistency of drug efficacy in the established cancer organoids and the patient responses in the clinic reached to 70% (7 out of 10 samples). Conclusions: We established a novel organoid culture system for TNBC patient samples after NAC, which was potentially a useful platform to explore molecular characteristics of TNBC patients after NAC and discover personalized drugs for intensive treatment.
Immunological profile could be responsible of the unusual long-lasting cutaneous-only breast cancer recurrence: An observational study.
Authors: Rebollo Joseba , González-Manzano Ramón , Sureda Manuel , Martínez Elena Ma , Monedero Elena , Bretcha Pedro , Brugarolas Antonio 
Published: June 2022

e13000 Background: A small number of breast cancer patients develops long-lasting loco-regional cutaneous recurrent disease with a delayed appearance of systemic disease. We recently have observed a favourable immunological signature in one patient and thereafter we looked back to the institutional series to formulate a possible hypothesis. Methods: Two datasets of resistant and metastatic solid tumors (362 Agilent microarrays and 169 RNA sequencing), have been studied. Three immunological signatures have been applied (T-cell inflamed, Cytolysis and TMM) and patients with at least one positive signature have been identified. Results: Preliminary evidence identified, from our genomic and transcriptomic advanced breast cancer database (73 patients and 80 procedures), three patients (4%) with loco-regional only cutaneous recurrent disease. Two patients (#1 and #2) were Hormone Receptor-negative, HER2 receptor-positive with a long-lasting breast cancer cutaneous recurrence (57 and 42 months, respectively) until bone (#1) or visceral (pleura and liver) (#2) progression. Patient #3 is a Hormone Receptor-positive, HER2-negative breast cancer that has recently developed an ipsilateral cutaneous (breast) recurrence so we do not have a follow up. Patient #1 had 4 transcriptomic tests, patient #2 had 2 tests and #3 one test. Biopsies were obtained from cutaneous lesions. According to our database, 25 out 80 procedures (31.25%) showed at least one favourable immunological signature (Table). In patients #1 and #2 with consecutive genomic testing, the immunological profile got worse with the resistance to therapies before systemic progression. Conclusions: According to our observation, a positive immunological signature was associated with a loco-regional cutaneous breast cancer recurrence and an unusually prolonged course of the disease. This observation should be confirmed in larger trials with more patients. Immunotherapy might play a role in the management of this clinical situation. None of these 3 patients had a triple negative phenotype for which immunotherapy has been found active. Ayers et al. J Clin Oncol 2017; 127 (8):2930-2940. Yang et al. Clin Cancer Res 2020; 26(8):3296-3306. Manzano et al. BMC Cancer 2021: 432.[Table: see text]
Palliative care among metastatic breast cancer patients in the end-of-life period in the U.S.
Authors: Subramaniam Divya S. , Zhang Zidong , Jenkins Alexandria , Hinyard Leslie J. 
Published: June 2022

e13002 Background: Research has shown that palliative care improves the quality of end of life care, and lowers associated costs for cancer patients. The purpose of this study was to determine utilization of palliative care consult (PCC) on or after date of metastasis to date of death, the association of emergency department (ED), intensive care unit (ICU) and chemotherapies among metastatic breast cancer (MBC) patients in the United States. Methods: We conducted a retrospective study using the de-identified electronic medical record data from a national healthcare informatics provider and insurer between January 1, 2000 and December 31, 2018. The MBC patients (age ≥ 18 years) who were diagnosed with a secondary neoplasm after the index diagnosis of breast cancer and deceased in the period of data capture were included. The cohort was split into the PCC groups, patients who had received at least one PCC on or after the date of metastasis through date of death; and the non-PCC group. The ED, ICU and chemotherapy encounters since metastasis were defined by ICD-9/10, HCPCS or CPT codes per encounter records. We quantified the ED and ICU visits within two months of death; and the antineoplastic chemotherapies within one and two months of death. Time from metastasis to death and utilization of services were compared between the PCC and the non-PCC groups using Whitney U-test and Chi-squared test. Results: 979 deceased MBC patients had at least one PCC and 1,636 did not at all. Overall, average patient age at the last admission was 68.7+/-12.9 years. The median time from metastasis to death was 9 (2 – 24) years. More than half of them were Caucasian (79.8%) and nearly half from the Midwest region (47.1%). Between the two groups, age distribution was not significantly different, but the PCC patients were more likely to have shorter time to death (8 vs 10 years), be African American (12.8% vs 9.8%), reside in Midwest (52.9% vs 43.7%) and have experienced complications since metastasis except for acute cerebrovascular events. Compared to the non-PCC patients, the PCC patients were more likely to use ED (52.2% vs 22.2%), ICU (12.5% vs 13.4%) within two months of death, and to receive chemotherapy within one and two months of death (17.7% vs 13.9% and 12.9% vs 6.0%, respectively). Conclusions: Our study found that only 38% of BC patients received at least one PCC following date of metastatic diagnosis. Findings highlight the need to increase PCC among MBC patients immediately following diagnosis to ensure appropriate care is provided and utilized. Furthermore, educational and informational interventions will need to be developed to boost PCC utilization among MBC patients.
Cytokine as an potential prognostic factor associated with absolute value of neutrophil and serum albumin in breast cancer patients.
Authors: Zhu Ye , Zhang Jingyi , Chen Chong , Tong Zhongsheng , Zhao Weipeng 
Published: June 2022

e13007 Background: Cytokines are involved in many inflammatory diseases through various ways and play an important role in tumor immune regulation. With the development of molecular biology these years, researchers have found that breast cancer is not only related to genetic and environmental factors, but also to the chronic inflammation and immunity. But at the moment，there are few studies on the prognostic evaluation of serum cytokines in breast cancer. The correlation between serum cytokines and leukocytes was not clear. The purpose of this study is to investigate the value of serum cytokines in prognosis of breast tumors and their relationship with leukocyte characters and serum albumin level. Methods: A total of 75 serum samples and clinicopathological data of breast cancer patients from Tianjin Medical University Cancer Institute and Hospital were collected. The expression levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-α, IFN-γ) in serum were detected by immunofluorescence method. The absolute value of different kinds of leukocyte were determined by automatic blood analyzer. The concentration of albumin (ALB) was determined by bromocresol green method (BCG method). Univariate Cox regression and multivariate Cox regression were used to analyze the influence of the above indexes and clinicopathological features on the prognosis of patients. The correlation between the expression of cytokines and the absolute value of various kinds of leukocyte and serum albumin was studied by using multiple regression analysis. Results: A multivariate Cox proportional risk model was established by including breast cancer stage, molecular typing, IL-10, IL-12p70, absolute value of neutrophil, serum albumin and dipeptide aminopeptidase. It showed that different breast cancer stage (HR=0.415, 95%CI 0.191-0.902, P=0.026), and IL-10 (HR=0.177, 95%CI 0.038-0.821, P=0.027) were independent prognostic factors, Luminal B breast cancer had a statistically significant impact on survival compared with triple negative breast cancer (HR=0.193, 95%CI 0.067-0.554, P=0.002). The effect of other variables on survival was not statistically significant (P>0.05). Multiple linear regression analysis model demonstrated that the absolute value of neutrophils (b=1.498, t =2.938, P=0.005) and serum albumin (b=1.253, t=2.777, P=0.007) had statistically significant differences on IL-10, but breast cancer stage (b=0.635, t=1.776, P=0.08) and dipeptide aminopeptidase had no significant difference (b=0.952, t=1.715, P=0.091). Conclusions: Serum IL-10 plays an important role in indicating the prognosis of patients with breast cancer and its expression level was closely correlated with absolute value of neutrophil and serum albumin.
Real-world survival outcomes associated with use of pertuzumab and trastuzumab emtansine (T-DM1) for HER2-positive (HER2+) metastatic breast cancer (MBC) in Brazilian private healthcare setting.
Authors: Dienstmann Rodrigo , Cruz Heloisa , Coelho Gonçalves Aline , Andrade Diocesio Alves Pinto de , Liedke Pedro Emanuel Rubini , Costa Rafael Brant , Dantas Loures da Costa Mario Alberto , Boukai Alexandre , Paes Flavia Rocha , Landeiro Luciana G. , Gimenes Daniel Luiz , Magalhaes Maria Cristina Figueroa , Resende Cristiano Augusto Andrade de , Reinert Tomas , Aguiar Junior Pedro N. , Paes Rafael , Costa e Silva Matheus , Ferrari Bruno Lemos , Mano Max S. 
Published: June 2022

e13022 Background: Breast cancer is a leading death cause of women in Brazil. There are increased concerns with limited access to innovative therapies and the effectiveness of these agents outside clinical trials. This study aims to assess practice patterns and real-world outcomes of patients with HER2+ metastatic breast cancer (MBC) treated in the largest network of community oncology practices of Brazil after the introduction of pertuzumab and T-DM1 in routine care. Methods: De-identified electronic medical records from Oncoclínicas Group were aggregated in a cloud-based central database that allows technology-based abstraction, whereby trained data curators qualify the information using mCODE standards. We included data from all patients with a confirmed diagnosis of HER2+ MBC treated from 2014 to 2021. The primary objective was median overall survival (OS) from diagnosis of metastatic disease and other endpoints included adoption of pertuzumab-based regimen and T-DM1 in the palliative setting and their median Time to Treatment Discontinuation (TTD) in a real-world scenario. Results: Out of 21,559 patients with BC in our database, 6,215 had HER2+ disease and 1,250 had MBC treated with at least one palliative anti-HER2 therapy. Median age at diagnosis was 56 years, 29% had de novo metastatic disease, 81% received 2nd line therapy and 47% a 3rd line or beyond. With a median follow-up of 2 years, median OS was 49 months (CI95% 44-59). We found a ten-fold increase in the proportion of patients receiving pertuzumab or T-DM1 in the last two years when compared to 2014-2015. Overall, 62% received a pertuzumab-based regimen, mostly in the 1st line (76%), with median TTD of 9.9 months (CI95% 9-13). T-DM1 was accessible to 22% of the patients, mostly in 2nd (28%) or 3rd line and beyond (50%), with median TTD of 10.2 months (CI95% 9-13). Conclusions: In the largest Brazilian real-world study of patients with HER2+ MBC treated in the private health system, we found similar outcomes as those reported in North-American and European cohorts, both in terms of OS and TTD with standard-of-care therapies. Adoption of pertuzumab and T-DM1 was fast, but there are still gaps in access and the need to optimize clinical positioning of new anti-HER2 therapies recently approved for clinical use.
Maintenance endocrine therapy prolonged progression-free survival of first-line chemotherapy with trastuzumab in advanced HR-positive, HER2-positive breast cancer patients.
Authors: Shen Xia-Bo , Wu Jia-Yi , Chen Ke-Yu , Fang Zi-Ru , Li Guang-Liang , Zou Wei-Bin , Wang Xiaojia , Shao Xi-Ying 
Published: June 2022

e13023 Background: Human epidermal growth factor receptor-2 (HER2) positive breast cancer is a growing concern due to the boom in anti-HER2 therapy. Trastuzumab as the most classic anti-HER2 therapy drug, combined with chemotherapy has become the standard first-line treatment for advanced HER2-positive (HER2+) patients. Although some real-world studies of trastuzumab have been reported, less is known about the role of hormone receptors (HR) in first-line combined therapy. For maintenance therapy after chemotherapy combined with anti-HER2 therapy, the guidance given by clinical trials is the maintenance of targeted therapy. However, for those with HER2+/HR-positive (HR+) breast cancer, whether adding endocrine maintenance therapy can benefit progression-free survival (PFS) in addition to anti-HER2 therapy still needs more research. Thus, the purpose of this study was to retrospectively analyze real-world data, determine the factors that influence the trastuzumab-based therapy in advanced HER2-positive breast cancer patients. Methods: We retrospectively collected the treatment information of advanced breast cancer patients underwent first-line chemotherapy with trastuzumab from 2012 to 2021 in Zhejiang Cancer Hospital. Kaplan–Meier analysis and Cox regression methods were used to calculate and compare the PFS. Results: The study finally enrolled 285 patients meeting the requirement, including 150 HER2+/HR-negative (HR-) and 135 HER2+/HR+ (triple-positive) patients. The median chemotherapy treatment cycles and trastuzumab cycles were 7 (6-8) and 12 (7-17) cycles, respectively. For triple-positive breast cancer, maintenance endocrine therapy was aslo given concurrently with trastusumab in 75 patients after chemotherapy and trastusumab. Overally, the median PFS of first-line treatment was 11.73 (10.16-13.30) months, which was consistent with literature reports. Multivariate analysis revealed that HR positive [hazard ratio, 0.69; 95% confidence interval (CI), 0.52–0.92; P= 0.010], and non-brain metastasis (hazard ratio, 0.54; 95% CI, 0.29–0.99; P= 0.048) were independent prognostic factors. Further Kaplan–Meier analysis demonstrated triple-positive patients with maintenance endocrine therapy significantly had longer PFS than triple-positive patients without maintenance endocrine therapy and HER2+/HR- patients (21.33m vs. 10.13m vs. 9.53m, respectively, P < 0.001). Conclusions: HR-positive was an independent prognostic factor for HER2-positive advanced breast cancer patients receiving first-line chemotherapy with trastuzumab. And endocrine therapy combined trastuzumab as Maintenance after chemotherapy prolonged PFS in HR-positive subgroup patients.