Breast Cancer Research and Treatment最新文献

{"title":"Impact of the COVID-19 pandemic on breast cancer surgeries in a Canadian population.","authors":"Gary Ko, Qing Li, Ning Liu, Eitan Amir, Andrea Covelli, Antoine Eskander, Vivianne Freitas, C Anne Koch, Jenine Ramruthan, Emma Reel, Amanda Roberts, Toni Zhong, Tulin D Cil","doi":"10.1007/s10549-024-07547-9","DOIUrl":"10.1007/s10549-024-07547-9","url":null,"abstract":"<p><strong>Purpose: </strong>The COVID-19 pandemic significantly impacted breast cancer (BC) surgeries. Most studies showing reduced BC surgical volumes during the pandemic are from single institutions, few have described volume changes in different types of surgical procedures. This study aimed to assess the impact of the pandemic on BC surgery volumes and types at a population level.</p><p><strong>Methods: </strong>Patients diagnosed with BC between January 1, 2018, and June 25, 2022, in Ontario, Canada, were analysed from population-based datasets. Time periods were defined as pre-pandemic (Jan 2018-Mar 2020), immediate pandemic (Mar-Jun 2020), and peri-pandemic (Jun 2020-Jun 2022). Weekly BC surgery volume and type (lumpectomy, mastectomy, or mastectomy with immediate reconstruction) were evaluated using segmented negative binomial regression models.</p><p><strong>Results: </strong>Among 44 226 patients, 50 440 surgeries were performed. Weekly BC surgeries decreased by 16.9% during the immediate pandemic compared to pre-pandemic levels (180.5 vs. 217.1; p = 0.03). Surgical volumes recovered to pre-pandemic levels by June 2021. Mastectomies represented a higher proportion of BC surgeries during the pandemic (31.1% pre, 36.3% immediate, 32.4% peri-pandemic; p < 0.01). The proportion of mastectomies with immediate reconstruction remained stable during the immediate pandemic but increased in the peri-pandemic (20.1% vs. 17%; p < 0.01).</p><p><strong>Conclusion: </strong>There was a significant reduction in all BC surgeries during the pandemic. Mastectomies accounted for a higher proportion of BC surgeries in the pandemic period however access to reconstruction was maintained. Surgical volumes recovered within a year despite ongoing pandemic hospitalizations. Future studies are needed to explore the pandemic's long-term impact on BC care.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"147-156"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The functional TNF-α^-308G > a single-nucleotide polymorphism (rs1800629): association with the predictive indices of breast cancer carcinogenesis.","authors":"Sherif Refaat, Hanan E Al-Rashidi, Rania A Abd El Azeem, Walaa E Nouh, Sahar Hamed, Zeinab R Attia","doi":"10.1007/s10549-024-07536-y","DOIUrl":"10.1007/s10549-024-07536-y","url":null,"abstract":"<p><strong>Background: </strong>Compared with all other cancer types, Breast cancer (BC) among women has now exceeded them all as the primary reason for cancer worldwide. The BC represents 11.7% of all cancer cases and accounts for a predestined 2.3 million new cases. It is the fourth primary reason for cancer-associated deaths in women. With a staggering 200-400% increase in the relative incidence of BC in Egypt, there is an urgent need for new diagnostic or predictive markers.</p><p><strong>Purpose: </strong>The current investigation aims to explore the connection of the functional TNF-α^-308G > A (rs1800629) single-nucleotide polymorphism (SNP) with different breast cancer predictive indices.</p><p><strong>Methods: </strong>The ARMS-PCR method was used for genotyping TNF-α^-308G > A SNP. Three groups were recruited for the study: 79 patients with benign breast inflammation (BBI); 163 with breast cancer (BC) and 144 controls (C).</p><p><strong>Results: </strong>The TNF-α^-308G > A SNP was distributed among different groups in a unique pattern; in the control group 63.9% of cases were in the GG, 34% were in the GA, and 2.1% were in the AA. The BC group had 14% GG, 79% GA, and 7% AA, while the BBI group had 24% GG, 76% GA, and 0% AA. The AA genotype and A allele represented a strong significant correlation with risk factors in the BC group (OR_AA: 14.67 [95% CI = 3.78-56.91] and OR_A: 0.27 [95% CI = 0.19-0.39], respectively; P < 0.0001) in contrast to the control group. However, in the BBI group, a strong significant correlation was noted with the GA genotype (OR_GA: 5.93 [95% CI = 3.18-11.04] P < 0.0001). In the BC group, the AA genotype shows a significant increase in Nottingham Prognostic Index (NPI) in positive ER and PR in contrast to the relevant negative ones (P = 0.02 and 0.002, respectively). However, the GA genotype significantly increased NPI in positive Her2 and metastatic patients (P = 0.03 and 0.01, respectively).</p><p><strong>Conclusion: </strong>This research is the first to correlate TNF-α^-308G > A (rs1800629) SNP in Egyptian BC patients. The A allele, GA & AA genotypes, and the Overdominant model of the TNF-α^-308G > A gene variants were recorded as prognostic risk factors for BC carcinogenesis.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"57-70"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease recurrence in patients undergoing mastectomy for ductal carcinoma in situ.","authors":"Marissa C Kuo, Jessica Sims, Odette K Solis, Ingrid M Meszoely, Raeshell S Sweeting, Ana M Grau, Kelly C Hewitt, Rondi M Kauffmann, Mark C Kelley, Rachel L McCaffrey","doi":"10.1007/s10549-024-07530-4","DOIUrl":"10.1007/s10549-024-07530-4","url":null,"abstract":"<p><strong>Purpose: </strong>With DCIS incidence on the rise, up to 30% of patients undergo mastectomy for Ductal carcinoma in situ (DCIS) (Nash and Hwang, in: Ann Surg Oncol 30(6):3206-3214, 2023). Local recurrence rates after mastectomy for DCIS are reportedly low, but risk factors for recurrence are not known (Kim et al., in: J Cancer Res Ther 16(6):1197-1202, 2020). We aim to define risk factors associated with ipsilateral breast cancer recurrence in patients undergoing mastectomy for DCIS.</p><p><strong>Methods: </strong>We aimed to identify risk factors that may contribute to recurrence of breast cancer following mastectomy for pure DCIS. We hypothesized that close or positive mastectomy margins, age at diagnosis, extent of breast disease and mutation carriers would be associated with increased risk of recurrence. We performed a retrospective chart review of patients who underwent unilateral or bilateral mastectomies for pure DCIS at a single academic tertiary referral center from 2013 to 2023.</p><p><strong>Results: </strong>There were 165 patients who met inclusion criteria with an average length of follow-up of 39.9 months. On final surgical pathology, the average span of DCIS was 33.7 mm (± 24.6 mm). Hormone receptor positive disease was identified in 80.6% of the patient cohort. For margin status, 23 patients (14%) had < 1 mm margins on final pathology and of those, 1 received adjuvant radiation therapy and 4 returned to the OR for re-excision. Only 1 (0.6%) patient had ipsilateral disease recurrence during the study period.</p><p><strong>Conclusion: </strong>Recurrence after mastectomy for pure DCIS is a rare event and in our study sample, only one recurrence occurred. Risk factors for recurrence appear unrelated to margin status, age, extent of DCIS, or pathogenic mutation (ElSherif et al., in Am J Surg 226(5):646-651, 2023).</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"675-679"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative analysis of pressure levels in manual lymphatic drainage across stages of breast cancer-related lymphedema: implications for optimized treatment protocols.","authors":"Naifang Xing, Daiqing Liu, Lufeng Chen, Guorong Wang, Yuan Tian, Chen Yang, Yingjie Leng, Xin Jiang, Chengxiang Li, Ruonan Xie, Zhuomiao Nie, Tian Zhang","doi":"10.1007/s10549-024-07540-2","DOIUrl":"10.1007/s10549-024-07540-2","url":null,"abstract":"<p><strong>Objective: </strong>To quantify the pressure levels necessary for effective Manual Lymphatic Drainage (MLD) in managing Breast Cancer-Related Lymphedema (BCRL) across various stages, and to contribute to the development of standardized protocols for MLD therapy.</p><p><strong>Methods: </strong>The study included 42 patients with BCRL (Stages I-III) and 14 certified lymphedema therapists. Forearms and upper arm circumferences were measured pre and post a 21-day MLD intervention. A tactile sensor system recorded the applied pressure during treatment. The data were preprocessed and statistically analyzed to assess pressure patterns and their stage-specific impacts on lymphedema.</p><p><strong>Results: </strong>The mean age of the patients was 52.4 years, and that of the therapists was 39.1 years. A statistically significant reduction in arm circumference was observed post-MLD treatment (P < 0.05). The pressure applied varied across stages: I _forearm 16.5-20.1 mmHg, I _{upper arm} 16.1-20.7 mmHg; II _forearm 16.6-19.8 mmHg, II _{upper arm} 19.7-23.8 mmHg; III _forearm 29.3-34.3 mmHg, III _{upper arm} 29.7-34.3 mmHg. No statistically significant difference was found between forearm and upper arm treatment pressures within Stages I (P = 0.283) and III (P = 0.08), while Stage II exhibited a significant difference (P < 0.001). Across the same treatment area, pressures for Stages I and II in the forearm were significantly lower than those in Stage III (P < 0.001). The treatment pressure differences between forearm stages I and II were not statistically significant (P > 0.05). Differences in upper arm treatment pressures across Stages I, II, and III were also statistically significant (P < 0.001).</p><p><strong>Discussion: </strong>The study provides quantitative evidence on the pressure ranges needed for MLD across different stages of BCRL. It highlights the importance for stage-specific pressure adjustments to optimize treatment outcomes. These findings contribute to the existing body of knowledge on MLD and offer valuable data that could inform the development of rehabilitation technologies, including intelligent robots and visualization systems, as well as enhance therapist training programs.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"95-103"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of distress and depression screening measures and other electronic health record information with adjuvant endocrine therapy persistence.","authors":"Joan M Neuner, Melinda Stolley, Sailaja Kamaraju, Jacob Tiegs, Rodney Sparapani, Vaia Makris, Kathryn E Flynn","doi":"10.1007/s10549-024-07513-5","DOIUrl":"10.1007/s10549-024-07513-5","url":null,"abstract":"<p><strong>Purpose: </strong>Few risk factors for early adjuvant endocrine discontinuation have been identified, but clinical trials suggest pre-AET symptom burden might be important. We sought to assess this in an academic practice.</p><p><strong>Methods: </strong>We examined baseline and up to five years of follow-up information for postmenopausal women with stage I-III hormone-receptor positive breast cancer 2014-2019 receiving oncologist prescriptions for AET. The Distress Thermometer (DT) and its problem list, the Patient Health Questionnaire 2/9 (PHQ 2/9), cancer extent of disease and treatments, comorbidities, sociodemographics, and pharmacy prescription fill dates were abstracted from the cancer registry and electronic health record (EHR). The association of these variables with early AET prescription fill discontinuation (prior to 5 years) was examined using survival analysis and Bayesian machine learning, with censoring for recurrence, death, or provider change.</p><p><strong>Results: </strong>Among the cohort of 961 women (mean 68.8 years, SD 2.88), 91.6% were white, 74.6% had Stage I disease, and 45.0% a pre-AET DT showing high distress (> 3). The median follow-up time was 820 (25, 75% 448,1282) days, and 29.6% discontinued early. Neither the DT score nor the PHQ 2/9 was associated with nonadherence, although three physical problems were modestly associated. Over 25% of women who stopped filling prescriptions did not have their prescriptions discontinued in the EHR.</p><p><strong>Conclusions: </strong>Several commonly available baseline EHR variables were not associated with early discontinuation, although some symptoms may have modest effects. Many women who discontinued still had EHR prescriptions, suggesting that physicians could use prescription fill information to intervene earlier.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"541-552"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pooled clinical trial analyses evaluating outcomes of HER2-low vs HER2-0 expression in patients with metastatic breast cancer following chemotherapy.","authors":"Elizabeth B Lamont, Emily Stein, Paolo Tarantino, Sara M Tolaney, Corinne Ahlberg, Krishna Chinnathambu, Jiezhi Qi, Jackie Bilan, Ruthie Davi, Lisa Ensign","doi":"10.1007/s10549-024-07581-7","DOIUrl":"10.1007/s10549-024-07581-7","url":null,"abstract":"<p><p>The therapeutic importance of subsetting patients with HER2-negative breast cancer according to their tumors' cellular HER2 expression (e.g., HER2-low vs. HER2-0) is relatively new, stemming from the dramatic results of the DESTINY-04 trial which established HER2-low expression as actionable. Most prior observational research of traditionally HER2-negative patients suggests that tumor behavior and biology do not vary according to HER2-low vs. HER2-0 expression, though some studies suggest otherwise. Here we studied this question in women with metastatic breast cancer (MBC) who were treated with standard single agent chemotherapy in the setting of clinical trials carried out in the pre-DESTINY-04 era. After pooling data from 142 female patients with MBC across historic clinical trials and categorizing them according to HER2 expression (i.e., HER2-0 or HER2-low), we evaluated associations between HER2 expression and the outcomes of both progression-free survival (PFS) and overall survival (OS) with both Kaplan-Meier and Cox proportional hazards methods. Studying data from an era when quantifying amounts of tumor HER2 expression in HER2-negative patients was neither standardized nor clinically actionable, we found no meaningful clinical differences in PFS or OS according to HER2-low vs. HER2-0 status, supporting prior findings of no biologic differences.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"11-14"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Dynamics of Breast Cancer Subtypes: The Role of FAM83H-AS1 Long Non-coding RNA in Breast Cancer Metastasis.","authors":"Mohammad Hossein Hashemi, Hassan Moaiery, Bahram Nikkhoo, Fatemeh Zamani, Soma Mahmoodian, Marzieh Soheili, Farzad Soleimani, Zhila Bahramirad, MohammadBagher KhademErfan, Bayazid Ghaderi, Mohammad Erfan Keyhani, Sherko Nasseri","doi":"10.1007/s10549-024-07603-4","DOIUrl":"https://doi.org/10.1007/s10549-024-07603-4","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer is the leading cause of cancer-related deaths in women. Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are emerging as major players in cancer biology, This study investigates the expression of FAM83H-AS1 in breast cancer and its association with tumor grade, hormone receptors, pathological diagnosis, and molecular markers related to epithelial-mesenchymal transition (EMT).</p><p><strong>Methods: </strong>The expression of the long non-coding RNA FAM83H-AS1 in 80 breast cancer patients was assessed using quantitative real-time PCR (qRT-PCR). Clinical significance was evaluated through histopathological and immunohistochemical analyses. The associations of FAM83H-AS1 expression with tumor grade, hormone receptor status, and epithelial-mesenchymal transition (EMT) markers were analyzed.</p><p><strong>Results: </strong>A positive correlation was observed between tumor grade and the expression of FAM83H-AS1, N-cadherin, E-cadherin, and vimentin, whereas FGF-18, TGF-β, and β-catenin were downregulated. Estrogen receptor positivity was associated with CLDN1 and Snail-1 expression, while HER2 positivity was linked to vimentin expression. Snail-1 expression correlated positively with Ki-67 levels. All genes except MMP2 were significantly associated with lymph node metastasis. Comparative analysis revealed significant differences in FGF-18, TGF-β, N-cadherin, β-catenin, and MMP2 expression among luminal A, luminal B, and triple-negative breast cancer (TNBC) subtypes. FAM83H-AS1 was upregulated in TNBC compared to luminal A and inflammatory breast cancer (IBC), although the difference was not statistically significant. TNBC Exhibited upregulation of TGF-β, N-cadherin, and β-catenin, suggesting their role in the aggressive nature of this subtype. In contrast, MMP2 was downregulated in TNBC compared to IBC, potentially indicating a suppressive role in tumor invasion in TNBC. Vimentin was upregulated in IBC compared to luminal A, indicating its involvement in IBC's aggressive behavior. MMP2 and MMP9 were significantly upregulated in IBC compared to luminal A.</p><p><strong>Conclusion: </strong> FAM83H-AS1 shows potential as a prognostic biomarker and therapeutic target, especially in TNBC and IBC, with implications for personalized breast cancer treatment strategies. Its expression correlates with tumor grade, hormone receptor status, and EMT markers, suggesting a role in cancer progression and metastasis.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world quality-of-life of patients with HR+/HER2- advanced breast cancer treated with palbociclib plus endocrine therapy: EORTC QLQ-C30 results from POLARIS.","authors":"Gabrielle B Rocque, Joanne L Blum, Yan Ji, Timothy Pluard, John Migas, Shailendra Lakhanpal, Erin Jepsen, Eric Gauthier, Yao Wang, Monica Z Montelongo, Joseph C Cappelleri, Meghan S Karuturi, Debu Tripathy","doi":"10.1007/s10549-024-07524-2","DOIUrl":"10.1007/s10549-024-07524-2","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate patient-reported health-related quality-of-life (QoL) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced/metastatic breast cancer (ABC) treated with palbociclib in the longitudinal real-world study, POLARIS.</p><p><strong>Methods: </strong>Data were prospectively collected from adult patients with HR+/HER2- ABC treated with palbociclib plus endocrine therapy (ET) in routine clinical practice. QoL was assessed with the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) and reported at baseline and months 6, 12, and 18. Data were expressed as absolute scores at a given time and change from baseline for global QoL and functional/symptom scales. Global Heath Status (GHS)/QoL scores were also determined across 6 patient subgroup categories (e.g., age, visceral disease status). Additionally, the proportions of patients with scores below (functional scales) or above (symptom scales) EORTC-validated thresholds reflecting clinical importance of a health problem were determined.</p><p><strong>Results: </strong>Among patients treated with palbociclib plus ET (N = 1250) who completed questionnaires at any of the study timepoints, mean GHS/QoL scores at months 6 (69.3), 12 (70.1), and 18 (69.9) were higher than baseline (64.0). Similar trends were observed for functional and symptom scales. Mean GHS/QoL scores over time were consistent across the evaluated subgroups. Decreases in the proportions of patients with clinically important functional impairment/symptoms were observed for most functional/symptom scales from baseline through month 18.</p><p><strong>Conclusion: </strong>Findings from this real-world study indicate patients with HR+/HER2- ABC treated with palbociclib plus ET maintain their QoL for at least 18 months.</p><p><strong>Clinical trial registration: </strong>NCT03280303; registered 12 September 2017.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"613-627"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pexidartinib and standard neoadjuvant therapy in the adaptively randomized I-SPY2 trial for early breast cancer.","authors":"Hope S Rugo, Mike Campbell, Christina Yau, A Jo Chien, Anne M Wallace, Claudine Isaacs, Judy C Boughey, Hyo S Han, Meredith Buxton, Julia L Clennell, Smita M Asare, Katherine Steeg, Amy Wilson, Ruby Singhrao, Jeffrey B Matthews, Jane Perlmutter, W Fraser Symmans, Nola M Hylton, Angela M DeMichele, Douglas Yee, Laura J Van't Veer, Donald A Berry, Laura J Esserman","doi":"10.1007/s10549-024-07555-9","DOIUrl":"10.1007/s10549-024-07555-9","url":null,"abstract":"<p><strong>Purpose: </strong>We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.</p><p><strong>Methods: </strong>I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response.</p><p><strong>Results: </strong>A total of 9 participants were randomized to receive pexidartinib with neoadjuvant paclitaxel before enrollment was halted due to a serious adverse event of vanishing bile duct syndrome. No participants received a full course of the study drug.</p><p><strong>Conclusion: </strong>Although there remains interest in agents targeting CSF-1, hepatic toxicity appears to be a limiting factor for their use in early breast cancer.</p><p><strong>Trial registration: </strong>NCT01042379 ( www.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT01042379 ).</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"487-492"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APX2009 sensitizes hypoxic breast cancer cells to doxorubicin by increasing its accumulation and caspase-3/7-mediated apoptosis.","authors":"Ísis Salviano Soares de Amorim, Daphne Pinheiro, Matheus da Silva Oliveira, Mariana Moreno de Sousa Rodrigues, Julia Silva José, Priscyanne Barreto Siqueira, Bruno Ricardo Barreto Pires, Adenilson de Souza da Fonseca, Andre Luiz Mencalha","doi":"10.1007/s10549-024-07512-6","DOIUrl":"10.1007/s10549-024-07512-6","url":null,"abstract":"<p><strong>Purpose: </strong>The association of targeted therapy with chemotherapy is encouraged to increase the treatment efficiency, especially in hypoxic triple-negative breast cancer. The APE1 redox activity has stood out as a potential tumor target. However, the effect of the association of the APE1 redox inhibitors with doxorubicin in hypoxia still needs to be evidenced. Therefore, our objective was to investigate the effect of the APX2009 (APE1 inhibitor) on the sensitization of breast cancer cells to doxorubicin in normoxia and hypoxia.</p><p><strong>Methods: </strong>The WST-1 assay was used to evaluate cell viability after APX2009 and doxorubicin application under normoxia and hypoxia conditions in the MCF-7 and MDA-MB-231 cells. Apoptosis was analyzed by annexin assay and detection of caspases-3/7 activity by luminescence-based assay. The clinical association between APE1 inhibition signature and doxorubicin sensitivity was evaluated by bioinformatics analyses.</p><p><strong>Results: </strong>MDA-MB-231 and MCF-7 cell lines were more sensitive to APX2009 in normoxia than in hypoxia. Co-treatment with APX2009 and doxorubicin in hypoxia further decreased the viability of triple-negative MDA-MB-231 cells than treatment alone, which was accompanied by doxorubicin intracellular accumulation, and increase of apoptotic cells percentage, and caspases-3/7 activity. Moderate association was found between APE1 inhibition signature and doxorubicin sensitivity in the hypoxic basal subtype.</p><p><strong>Conclusion: </strong>The findings suggest that APX2009 sensitizes the MDA-MB-231 cells to doxorubicin in hypoxia by doxorubicin intracellular accumulation and caspases-3/7-mediated apoptosis.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"533-540"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}