{"title":"The USP8/CEP55/CHMP6 Axis Orchestrates Triple-Negative Breast Cancer Progression by Regulating Ferroptosis and Macrophage M2 Polarization.","authors":"Lin Wang, Ye Wang, Changgen Liu, Yixin Zhao","doi":"10.1016/j.clbc.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.08.003","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) carries a substantial risk of recurrence and metastasis, posing significant threats to patients' health and quality of life. Centrosomal protein 55 (CEP55) has been demonstrated to exhibit elevated expression levels in TNBC. However, its molecular regulatory mechanism in TNBC remains unclear.</p><p><strong>Methods: </strong>Bioinformatics databases, qRT-PCR, and Western blot were employed to analyze CEP55 expression in TNBC tissues and cells. EdU assays, flow cytometry, and Transwell assays were utilized to monitor cell proliferation, apoptosis, and invasion. Subsequently, macrophage polarization was detected by flow cytometry. Fe<sup>2+</sup>, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels were determined using corresponding kits. Immunoprecipitation (IP) was used to detect the ubiquitination level of CEP55, and co-IP was applied to confirm the interaction between CEP55 and Charged Multivesicular Body Protein 6 (CHMP6). Finally, a xenograft tumor model was established, and immunohistochemistry (IHC) was conducted to evaluate the expression of specific proteins.</p><p><strong>Results: </strong>CEP55 levels were increased in TNBC tissues and cells. Silencing CEP55 repressed TNBC cell proliferation, invasion, and macrophage M2 polarization, and facilitated cell apoptosis and ferroptosis. Additionally, ubiquitin-specific protease 8 (USP8) maintained CEP55 stability through deubiquitination, and CEP55 overexpression reversed the cellular effects caused by USP8 knockdown. Moreover, CEP55 bound to CHMP6 to promote its expression, thereby facilitating the malignant progression of TNBC cells. CEP55 overexpression abolished the inhibitory influence of USP8 silencing on tumor growth in vivo.</p><p><strong>Conclusion: </strong>USP8 stabilized CEP55 expression through deubiquitination, and CEP55 further promoted CHMP6 expression to inhibit ferroptosis progression, thereby facilitating macrophage M2 polarization and malignant biological behaviors of TNBC cells.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029015","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":"Mechanistic Insights and Therapeutic Implications of Endothelial Nitric Oxide Synthase and Reactive Oxygen Species in Breast Cancer.","authors":"Mohammed Dlshad Mohsin, Abbas Salihi","doi":"10.1016/j.clbc.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.08.004","url":null,"abstract":"<p><p>Breast cancer (BC) remains a significant health problem globally, with complex underlying processes that are not fully understood. This study investigates the intricate relationship between endothelial nitric oxide synthase (eNOS) and reactive oxygen species (ROS) in the progressions of BC. Here we examine the essential roles of superoxide (O2·¯), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), and hydroxyl free radicals (OH·) in promoting tumor development, angiogenesis, and metastasis. In addition, this review also analyzes the significant role of eNOS in BC, which highlighting its activation by estrogen and the impact of eNOS gene polymorphisms on cancer risk. Furthermore, we elucidate the mechanisms of eNOS uncoupling, primarily focusing on the deficiency of tetrahydrobiopterin (BH4), the depletion of L-Arginine (L-Arg), and the buildup of asymmetric dimethylarginine (ADMA). This extensive study provides novel insights into the molecular mechanisms connecting oxidative stress and NO signaling in BC. It identifies prospective targets for innovative treatment strategies. Hence, the outcomes of the study may highlight the importance of comprehending the complex balance between eNOS activity and ROS production in the progression of BC. This provides the foundation for further studies and targeted therapies in BC treatment.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945009","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}
Nicole L Brown, Ann Tivey, Caroline Wilson, Fiona Britton, Sacha J Howell
{"title":"Re: Bridging Gaps in Remote Cancer Care: Commentary on the Adjuvant Abemaciclib Monitoring Model.","authors":"Nicole L Brown, Ann Tivey, Caroline Wilson, Fiona Britton, Sacha J Howell","doi":"10.1016/j.clbc.2025.08.005","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.08.005","url":null,"abstract":"","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944834","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}
Gu-Yue Liu, Dong-Ping Huang, Can Ge, Xiao-Yu Li, Fei Chen, Jia-Shu Fan, Huan-Ping Tu
{"title":"SPON2 acts as a tumor promoter in HR-positive/HER2-negative breast cancer by regulating β-catenin signaling.","authors":"Gu-Yue Liu, Dong-Ping Huang, Can Ge, Xiao-Yu Li, Fei Chen, Jia-Shu Fan, Huan-Ping Tu","doi":"10.1016/j.clbc.2025.07.030","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.07.030","url":null,"abstract":"<p><strong>Background: </strong>Spondin-2 (SPON2) expression is associated with various types of cancer, but its role in breast cancer (BC) remains ambiguous, especially in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) BC.</p><p><strong>Methods: </strong>The expression of SPON2 in HR+/HER2- BC tissues and adjacent tissues was detected using immunohistochemical staining and western blotting. Cell proliferation and migration were assessed via CCK-8 assay, EdU assay, and transwell assay. Animal studies were performed to assess the effect of SPON2 knockdown on tumor growth.</p><p><strong>Results: </strong>Herein, increased expression of SPON2 was found in HR+/HER2- BC, and silencing SPON2 suppressed cell proliferation, clonogenicity, and migration, whereas SPON2 overexpression had the opposite effects. Notably, SPON2 knockdown significantly suppressed tumor growth in a xenograft tumor assay. Mechanistically, a reduction in SPON2 expression inhibited β-catenin activation, whereas its overexpression promoted β-catenin-mediated proliferation and migration.</p><p><strong>Conclusion: </strong>These data indicate that SPON2 plays oncogenic roles in HR+/HER2- BC via activating the β-catenin pathway, and may represent a potential therapeutic target for patients diagnosed with HR+/HER2- BC.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944859","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}
Paola Villa, Chiara Cassani, Rossella E Nappi, Valentina E Bounous, Dorella Franchi, Maurizio Guida, Inbal Dona Amar, Luca Cova, Alessandra Di Lelio, Giusi Graziano, Valentina Trionfera, Maria Cristina Meriggiola
{"title":"Quality of life and Satisfaction With Ospemifene for Treating Vulvovaginal Atrophy in Breast Cancer Survivors: Six-Month Results From the PatiEnt SatisfactiON StudY (PEONY).","authors":"Paola Villa, Chiara Cassani, Rossella E Nappi, Valentina E Bounous, Dorella Franchi, Maurizio Guida, Inbal Dona Amar, Luca Cova, Alessandra Di Lelio, Giusi Graziano, Valentina Trionfera, Maria Cristina Meriggiola","doi":"10.1016/j.clbc.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.08.001","url":null,"abstract":"<p><strong>Objective: </strong>Breast cancer (BC) survivors often experience vulvovaginal atrophy (VVA) due to endocrine therapies, affecting quality of life (QoL) and well-being. We aimed to evaluate impact of ospemifene treatment in postmenopausal women with history of BC and moderate to severe VVA.</p><p><strong>Methods: </strong>PEONY is a real-world, prospective, multicenter study. Participants completed questionnaires at baseline, after 3 and 6 months. Treatment satisfaction score was the primary outcome. As secondary outcomes, symptoms severity, day-to-day impact of vaginal aging scale, female sexual function index, female sexual distress scale-revised, and SF-12® Health survey were investigated.</p><p><strong>Results: </strong>Sixty-four women with a mean age of 56.4 ± 7.2 years (41.9% with severe VVA) either initiated (35.9%) or continued (64.1%) ospemifene. Treatment satisfaction significantly improved over 6 months, with mean score rising from 7.1 to 7.8 (P = .047). The odds of moderate to severe symptoms, such as vaginal dryness, pain and bleeding during sexual intercourse, genital discomfort during physical activity, burning, and itching, decreased by 70% to 90% at 6 months, as well as recurrent urinary tract infections and cystitis associated with sexual intercourse (by 80% and 90%). QoL measurements showed significant improvements in physical health and daily functioning, although mental health improvements were not statistically significant. Likelihood of sexual distress decreased by 40%. Although overall sexual function remained unchanged, specific domains such as lubrication and pain showed improvement.</p><p><strong>Conclusion: </strong>Ospemifene is effective and well-tolerated for treating moderate to severe VVA of women with history of BC. However, a comprehensive and multidisciplinary approach is needed to improve sexual function of BC survivors treated for VVA.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005977","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}
Congting Hu, Jia Liu, Suyan Liu, Pingping Peng, Jiaqin Cai, Xiaoxia Wei, Hong Sun
{"title":"Mendelian Randomization Study: The Impact of Gut Microbiota on Survival in HR+ Breast Cancer Patients Under Different Treatment Regimens Through the Modulation of Immune Cell Phenotypes.","authors":"Congting Hu, Jia Liu, Suyan Liu, Pingping Peng, Jiaqin Cai, Xiaoxia Wei, Hong Sun","doi":"10.1016/j.clbc.2025.07.024","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.07.024","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that the gut microbiota (GM) may influence the progression of breast cancer by modulating immune responses. Given the vast diversity of GM and immune cell phenotypes, this study aimed to utilize the most advanced and comprehensive data to explore the causal relationships among the GM, immune cell phenotypes, and survival rates in hormone receptor-positive (HR+) breast cancer patients under different treatment regimens.</p><p><strong>Methods: </strong>We investigated the causal relationships between the GM, immune cell phenotypes, and survival rates in HR+ breast cancer patients treated with 11 distinct therapeutic strategies using Mendelian randomization. Inverse variance weighted analysis served as the primary statistical method. Additionally, we explored whether immune cell phenotypes act as mediators in the pathway from the GM to HR+ breast cancer survival rates.</p><p><strong>Results: </strong>In this comprehensive study, we identified 116 distinct GM species that established causal links with survival rates across 11 different subgroups of HR+ breast cancer patients. Furthermore, we discovered 13 potential pathways through which the GM might influence immune cell phenotypes, thereby affecting patient survival rates.</p><p><strong>Conclusion: </strong>The GM is causally associated with survival rates in HR+ breast cancer patients treated with 11 different therapeutic strategies, and immune cell phenotypes serve as mediators in the pathway from the GM to HR+ breast cancer survival rates.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014035","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":"De-escalating Surgery, Escalating Radiation in Axillary Management of Breast Cancer: Progress or Lateral Shift?","authors":"Akshay Nagwani, Kanika Kapur, Pankaj Kumar Garg","doi":"10.1016/j.clbc.2025.07.029","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.07.029","url":null,"abstract":"","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945073","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}
Amparo Garcia-Tejedor, Carla Julià, Julia Ciria, Rodrigo Guevara-Peralta, Carlos Ortega-Expósito, Raul Ortega, Agostina Stradella, Héctor Pérez-Montero, Gabriel Reyes-Juncan, Ana Benitez, Anna Guma, Juan Azcarate, Miriam Campos, Maria J Plà, Evelyn Martinez, Sonia Pernas, Jordi Ponce, Catalina Falo
{"title":"Prognostic Outcomes by Axillary Approach in Lobular and Ductal Breast Cancer With Sentinel Node Macrometastases: A Retrospective Cohort Study.","authors":"Amparo Garcia-Tejedor, Carla Julià, Julia Ciria, Rodrigo Guevara-Peralta, Carlos Ortega-Expósito, Raul Ortega, Agostina Stradella, Héctor Pérez-Montero, Gabriel Reyes-Juncan, Ana Benitez, Anna Guma, Juan Azcarate, Miriam Campos, Maria J Plà, Evelyn Martinez, Sonia Pernas, Jordi Ponce, Catalina Falo","doi":"10.1016/j.clbc.2025.07.022","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.07.022","url":null,"abstract":"<p><strong>Purpose: </strong>To compare survival outcomes between patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma non-special type (NST) presenting with sentinel lymph node biopsy (SLNB)-detected macrometastases in early-stage breast cancer.</p><p><strong>Materials and methods: </strong>A retrospective cohort study was conducted including 364 cN0 breast cancer patients with SLNB-detected macrometastases who underwent surgical treatment between July 2011 and December 2023. Patients were categorized as NST (n = 250) or ILC (n = 108). SLNB was the primary axillary staging procedure, with axillary lymph node dissection (ALND) performed according to predefined clinical criteria. Univariate and multivariate Cox regression analyses were used to identify predictors of pN2-pN3. Survival outcomes were assessed using Kaplan-Meier curves and compared with log-rank tests.</p><p><strong>Results: </strong>ILC patients presented with larger tumors, higher rates of multifocality, and greater axillary nodal involvement compared to NST. Surgery was more frequently mastectomy and ALND. pN2-N3 was identified in 12% of cases, with pT3 stage, ILC histology, and lymphovascular invasion as independent predictors. After a median follow-up of 7.6 years, the ILC group exhibited higher overall mortality (19.4% vs. 9.6%) and deaths attributed to systemic progression (57% vs. 29%). Ten-year distant disease-free survival and breast cancer-specific survival were significantly lower in the ILC cohort (63% vs. 87% and 65% vs. 93%, respectively; P < .05). Although 10-year overall survival was lower in ILC (54% vs. 79%), statistical significance was only observed in patients with advanced nodal disease (pN2-N3).</p><p><strong>Conclusions: </strong>ILC is associated with more advanced axillary burden and significantly worse long-term oncologic outcomes compared to NST carcinoma when macrometastases are present at SLNB.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944778","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}
Britt A M Jansen, Claudia A Bargon, Danny A Young-Afat, Annemiek Doeksen, Teun Teunis
{"title":"Minimal Clinically Important Differences in Scales Measuring Decision Uncertainty, Distress After a Traumatic Event, Body Image and Health Status Among Women With Breast Cancer Having Surgery.","authors":"Britt A M Jansen, Claudia A Bargon, Danny A Young-Afat, Annemiek Doeksen, Teun Teunis","doi":"10.1016/j.clbc.2025.07.021","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.07.021","url":null,"abstract":"<p><strong>Background: </strong>The smallest clinically relevant change (ie, minimal clinically important difference, MCID) for several valuable PROMs for women undergoing breast cancer surgery is unknown. Therefore, this study evaluated the smallest clinically relevant change for decision uncertainty, distress after traumatic events, body image, and health status in women diagnosed with breast cancer considering surgery.</p><p><strong>Patients and methods: </strong>Between August 2020 and October 2022, we included 123 women with breast cancer considering surgical treatment. Women completed the decisional conflict scale (DCS), impact of event scale (IES), body image scale (BIS), and 36-Item Short Form (SF-36) after their first visit, and 4-6 weeks and 6 months after surgery. The MCID was calculated using the anchor-based method. For the MCID to be reliable, it needs to be greater than the minimum detectable change (MDC).</p><p><strong>Results: </strong>The MCID for decision uncertainty (8.6) was smaller than the MDC (22). MCID values were 11 and 12 (MDC 8.4) for improvement in cancer-specific distress (IES), 2.5 and 6.5 (MDC 2.6) for deterioration in body image (BIS) and 27 and 14 (MDC 12) for deterioration in health status (SF-36) at 4 to 6 weeks and 6 months after surgery, respectively.</p><p><strong>Conclusion: </strong>This study successfully determined MCIDs for several PROMs. For IES, BIS, and SF-36 the MCID seems reliable, while the DCS cannot reliably capture a clinically relevant change. The MCID values may be useful when assessing clinically relevant changes over time, interpreting treatment effects, and trial sample size determination.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945038","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}
Marcelo Antonini, André Mattar, Marcelo Madeira, Letícia Xavier Félix, Julio Antonio Pereira de Araújo, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antonio Luis Frasson, Eduardo Camargo Millen, Marina Diógenes Teixeira, Larissa Chrispim de Oliveira, Marcellus do Nascimento Moreira Ramos, Gil Facina, Rogério Fenile, Henrique Lima Couto, Sabrina Monteiro Rondelo, Leonardo Ribeiro Soares, Ruffo de Freitas, Renata Arakelian, Vitoria Rassi Mahamed Rocha, Renata Montarroyos Leite, Luiz Henrique Gebrim
{"title":"Prognostic Impact of Real-World Immunohistochemical Changes in Breast Cancer Treated with Neoadjuvant Chemotherapy.","authors":"Marcelo Antonini, André Mattar, Marcelo Madeira, Letícia Xavier Félix, Julio Antonio Pereira de Araújo, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antonio Luis Frasson, Eduardo Camargo Millen, Marina Diógenes Teixeira, Larissa Chrispim de Oliveira, Marcellus do Nascimento Moreira Ramos, Gil Facina, Rogério Fenile, Henrique Lima Couto, Sabrina Monteiro Rondelo, Leonardo Ribeiro Soares, Ruffo de Freitas, Renata Arakelian, Vitoria Rassi Mahamed Rocha, Renata Montarroyos Leite, Luiz Henrique Gebrim","doi":"10.1016/j.clbc.2025.07.023","DOIUrl":"https://doi.org/10.1016/j.clbc.2025.07.023","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the rate and types of immunohistochemical (IHC) changes after neoadjuvant chemotherapy (NAC) and their influence on disease-free survival (DFS) and overall survival (OS) in breast cancer patients, with a focus on conversions such as HR+/HER-2+ to HR-/HER-2- and their implications for treatment adjustments.</p><p><strong>Methods: </strong>This retrospective cohort study included 369 female patients aged 18 years or older with nonmetastatic breast cancer treated with NAC between January 2011 and January 2023. Patients who did not achieve complete pathological response were evaluated for changes in IHC profiles, including hormone receptor (HR) status, HER-2 expression, and Ki-67 index. Prognostic outcomes were assessed using Kaplan-Meier survival analysis and multivariate Cox regression models.</p><p><strong>Results: </strong>IHC changes were observed in 41.7% of patients. Among those initially classified as HR-/HER-2-, 50.9% gained HR expression, and 14.1% acquired HER-2 expression. In HR+/HER-2+ cases, 70.8% experienced a loss of HER-2 expression. Patients with HER-2+ tumors exhibited more frequent IHC changes compared to HER-2- cases (P < .0001). After a median follow-up of 47.7 months, local recurrences occurred in 10.3% of patients, distant metastases in 29.5%, and 25.5% had died. Patients with IHC changes demonstrated significantly worse DFS and OS (P = .002), with the poorest outcomes associated with conversion to HR-/HER-2- (P < .001).</p><p><strong>Conclusion: </strong>Post-NAC IHC changes are common and associated with poor prognosis, especially in patients losing HR and HER-2 expression. Monitoring IHC shifts is critical for guiding personalized treatment and improving prognostic evaluation.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944445","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}