Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.012
Yi-Jing Fan , Hui-Qian Xu , Hong Li , Zi-rui Zhang , Shu-Fang Zhang , Ai-Jun Du , Li-zhi Zhou , Yang Wang
Background
Breast cancer-related lymphedema (BCRL) is a relatively common and harmful complication after breast cancer surgery, and there is currently no effective cure. We hypothesized that, compared with the control group, 12 weeks of resistance exercise at different intensities could reduce the incidence of BCRL after axillary lymph node dissection.
Methods
114 breast cancer patients undergoing axillary lymph node dissection were randomly divided into a Control Group (CG), a Low-to-Moderate Intensity Exercise Group (L-MIEG, 40%-70% 1-RM) and a Moderate-to-High Intensity Exercise Group (M-HIEG, 60%-85% 1-RM).
Results
(1) The 12-month cumulative BCRL incidence was higher in the CG (16.3%, 6/37) than in the L-MIEG (8.3%, 3/36) and M-HIEG (5.5%, 2/37). (2) Postintervention and at 6-and 12- month follow-ups, both intervention groups had smaller interlimb differences than the CG (P < .05), and the M-HIEG had smaller differences at 6-month than the L-MIEG (P < .05). (3) InBody analysis showed both intervention groups outperformed CG in segmental water differences, extracellular water (ECW), and single-frequency bioelectrical impedance analysis (SFBIA) (P < .05), and the M-HIEG was better at 6-month (P < .05). (4) At 6-and 12-month follow-ups, both intervention groups improved grip strength more than CG (P < .05), and the M-HIEG was superior at 12 months (P < .05).
Conclusions
Different- intensity resistance exercises benefit BCRL prevention, with M-HIEG being more effective.
{"title":"Effects of Resistance Training at Different Intensities on Preventing Breast Cancer-Related Lymphedema: A 1-Year Randomized Controlled Trial","authors":"Yi-Jing Fan , Hui-Qian Xu , Hong Li , Zi-rui Zhang , Shu-Fang Zhang , Ai-Jun Du , Li-zhi Zhou , Yang Wang","doi":"10.1016/j.clbc.2025.07.012","DOIUrl":"10.1016/j.clbc.2025.07.012","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer-related lymphedema (BCRL) is a relatively common and harmful complication after breast cancer surgery, and there is currently no effective cure. We hypothesized that, compared with the control group, 12 weeks of resistance exercise at different intensities could reduce the incidence of BCRL after axillary lymph node dissection.</div></div><div><h3>Methods</h3><div>114 breast cancer patients undergoing axillary lymph node dissection were randomly divided into a Control Group (CG), a Low-to-Moderate Intensity Exercise Group (L-MIEG, 40%-70% 1-RM) and a Moderate-to-High Intensity Exercise Group (M-HIEG, 60%-85% 1-RM).</div></div><div><h3>Results</h3><div>(1) The 12-month cumulative BCRL incidence was higher in the CG (16.3%, 6/37) than in the L-MIEG (8.3%, 3/36) and M-HIEG (5.5%, 2/37). (2) Postintervention and at 6-and 12- month follow-ups, both intervention groups had smaller interlimb differences than the CG (<em>P</em> < .05), and the M-HIEG had smaller differences at 6-month than the L-MIEG (<em>P</em> < .05). (3) InBody analysis showed both intervention groups outperformed CG in segmental water differences, extracellular water (ECW), and single-frequency bioelectrical impedance analysis (SFBIA) (<em>P</em> < .05), and the M-HIEG was better at 6-month (<em>P</em> < .05). (4) At 6-and 12-month follow-ups, both intervention groups improved grip strength more than CG (<em>P</em> < .05), and the M-HIEG was superior at 12 months (<em>P</em> < .05).</div></div><div><h3>Conclusions</h3><div>Different- intensity resistance exercises benefit BCRL prevention, with M-HIEG being more effective.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 204-212"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803721","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.030
Gu-yue Liu, Dong-ping Huang, Can Ge, Xiao-yu Li, Fei Chen, Jia-shu Fan, Huan-ping Tu
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"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":"10.1016/j.clbc.2025.07.030","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 298-305"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.008
Grace H. Amaden , Kelly A. Hyland , Joseph G. Winger , Sarah A. Kelleher , Allison K. Diachina , Shannon N. Miller , Kelly Westbrook , Gretchen Kimmick , Linda Sutton , Mei R. Fu , Tamara J. Somers
Purpose
To examine the relationship of lymphedema with pain, physical function, and demographic and medical variables in women with breast cancer and pain.
Methods
Secondary analysis of baseline data from a study of women with breast cancer and pain. Self-report questionnaires assessed lymphedema, pain severity, pain medication use behavior, pain-related cognitions (ie, pain self-efficacy, pain catastrophizing), and physical function (ie, basic and intermediate activities of daily living (ADLs)). Demographic and medical variables were extracted from the medical record. Univariate analyses examined relationships among lymphedema and variables of interest.
Results
Women (N = 327, Mage = 57 years, 63% White) reported moderate pain severity (M = 4.04). Twenty-six percent of women (n = 85) reported having lymphedema. Women with lymphedema endorsed greater pain severity (P = .007) and pain catastrophizing (P = .015) than women without lymphedema; groups did not differ on pain medication use or pain self-efficacy. Women with lymphedema reported a reduced capacity to complete intermediate ADLs compared to women without lymphedema (P = .044); groups did not differ on ability to complete basic ADLs. Women with lymphedema were more likely to be non-White, have lower educational attainment, have undergone lymph node removal or dissection, and received radiation therapy.
Conclusion
In women with breast cancer and moderate pain, lymphedema is associated with greater pain severity and pain catastrophizing, and decreased ability to complete intermediate ADLs. Women with lymphedema and pain may benefit from tailored, accessible cognitive-behavioral-physiological interventions to improve self-management (eg, Pain Coping Skills Training, interventions to promote lymph flow and reduce inflammation). Disparities in lymphedema prevalence by race and education warrant further exploration.
{"title":"Examining the Interrelationships of Lymphedema with Pain, Physical Function, and Demographic and Medical Variables in Women with Breast Cancer and Pain","authors":"Grace H. Amaden , Kelly A. Hyland , Joseph G. Winger , Sarah A. Kelleher , Allison K. Diachina , Shannon N. Miller , Kelly Westbrook , Gretchen Kimmick , Linda Sutton , Mei R. Fu , Tamara J. Somers","doi":"10.1016/j.clbc.2025.07.008","DOIUrl":"10.1016/j.clbc.2025.07.008","url":null,"abstract":"<div><h3>Purpose</h3><div>To examine the relationship of lymphedema with pain, physical function, and demographic and medical variables in women with breast cancer and pain.</div></div><div><h3>Methods</h3><div>Secondary analysis of baseline data from a study of women with breast cancer and pain. Self-report questionnaires assessed lymphedema, pain severity, pain medication use behavior, pain-related cognitions (ie, pain self-efficacy, pain catastrophizing), and physical function (ie, basic and intermediate activities of daily living (ADLs)). Demographic and medical variables were extracted from the medical record. Univariate analyses examined relationships among lymphedema and variables of interest.</div></div><div><h3>Results</h3><div>Women (<em>N</em> = 327, M<sub>age</sub> = 57 years, 63% White) reported moderate pain severity (<em>M</em> = 4.04). Twenty-six percent of women (<em>n</em> = 85) reported having lymphedema. Women with lymphedema endorsed greater pain severity (<em>P</em> = .007) and pain catastrophizing (<em>P</em> = .015) than women without lymphedema; groups did not differ on pain medication use or pain self-efficacy. Women with lymphedema reported a reduced capacity to complete intermediate ADLs compared to women without lymphedema (<em>P</em> = .044); groups did not differ on ability to complete basic ADLs. Women with lymphedema were more likely to be non-White, have lower educational attainment, have undergone lymph node removal or dissection, and received radiation therapy.</div></div><div><h3>Conclusion</h3><div>In women with breast cancer and moderate pain, lymphedema is associated with greater pain severity and pain catastrophizing, and decreased ability to complete intermediate ADLs. Women with lymphedema and pain may benefit from tailored, accessible cognitive-behavioral-physiological interventions to improve self-management (eg, Pain Coping Skills Training, interventions to promote lymph flow and reduce inflammation). Disparities in lymphedema prevalence by race and education warrant further exploration.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 179-186"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774777","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.009
Mattia A. Mahmoud , Oluwadamilola M. Fayanju , Anne Marie McCarthy , Carla R. Zeballos Torrez , Christine E. Edmonds
Purpose
Breast density is recognized as a well-established risk factor for breast cancer, influencing screening recommendations. While quantitative measures of breast density have been developed to address limitations of qualitative measures, the role of racial differences in quantitative measures and their effect on breast cancer risk, especially in Black women, remains unclear. Additionally, while background parenchymal enhancement (BPE) is an established as a predictor of breast cancer risk, no research has been conducted to investigate whether the impact of BPE varies by race or ethnicity. This perspective reviews existing data on BPE, specifically its relationship with breast density and breast cancer risk and emphasizes the need for further investigation in Black women.
Discussion
Current supplemental screening methods are heavily reliant on qualitative breast density assessments, which may disadvantage Black women. Although BPE has been significantly associated with breast cancer risk independent of breast density, no studies were found that explored the relationship between BPE and breast cancer risk in Black women.
Conclusion
The limited data on absolute quantitative density measures, such as dense volume, which could improve screening practices, is highlighted in this review. While BPE is well-established as a breast cancer risk factor, further research is needed to investigate racial differences in BPE and its association with breast cancer risk, particularly among Black women.
{"title":"Exploring Imaging Biomarkers to Improve Equity in Supplemental and High-Risk Breast Cancer Screening Between Black and White Women: A Perspective on Background Parenchymal Enhancement and Breast Density","authors":"Mattia A. Mahmoud , Oluwadamilola M. Fayanju , Anne Marie McCarthy , Carla R. Zeballos Torrez , Christine E. Edmonds","doi":"10.1016/j.clbc.2025.07.009","DOIUrl":"10.1016/j.clbc.2025.07.009","url":null,"abstract":"<div><h3>Purpose</h3><div>Breast density is recognized as a well-established risk factor for breast cancer, influencing screening recommendations. While quantitative measures of breast density have been developed to address limitations of qualitative measures, the role of racial differences in quantitative measures and their effect on breast cancer risk, especially in Black women, remains unclear. Additionally, while background parenchymal enhancement (BPE) is an established as a predictor of breast cancer risk, no research has been conducted to investigate whether the impact of BPE varies by race or ethnicity. This perspective reviews existing data on BPE, specifically its relationship with breast density and breast cancer risk and emphasizes the need for further investigation in Black women.</div></div><div><h3>Discussion</h3><div>Current supplemental screening methods are heavily reliant on qualitative breast density assessments, which may disadvantage Black women. Although BPE has been significantly associated with breast cancer risk independent of breast density, no studies were found that explored the relationship between BPE and breast cancer risk in Black women.</div></div><div><h3>Conclusion</h3><div>The limited data on absolute quantitative density measures, such as dense volume, which could improve screening practices, is highlighted in this review. While BPE is well-established as a breast cancer risk factor, further research is needed to investigate racial differences in BPE and its association with breast cancer risk, particularly among Black women.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 187-194"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774778","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.005
Yasmin A. Civil , Nora D. Purcell , Ralph de Vries , Arlene L. Oei , Victor L.J.L. Thijssen , Tanja D. de Gruijl , Berend J. Slotman , Famke L. Schneiders , H.J.G. Desirée van den Bongard
High tumor-infiltrating lymphocytes (TILs) levels in triple-negative and HER2-positive breast cancer are associated with better survival outcomes, highlighting its potential as prognostic biomarkers. Radiotherapy can also trigger immune cell infiltration. This systematic review evaluates the prognostic value of TILs in radiotherapy-treated breast cancer patients. A literature search (in PubMed, Embase and Web of Science) was performed up to April 5, 2024 (PROSPERO registration CRD42024401741). Two independent reviewers screened articles according to predefined criteria, resolving discrepancies through consensus. The collected outcomes were prognostic value of TILs for ipsilateral breast tumor recurrence (IBTR), any recurrence, distant metastasis (DM), overall survival (OS) and disease-free survival (DFS). Of 10,927 records, 11 studies (3899 patients) were included. Patients underwent lumpectomy or mastectomy, with or without postoperative radiotherapy. Three studies examined neoadjuvant partial breast irradiation. The stroma threshold for high vs. low TILs ranged from 5 to 50%, with most patients (73%) having low TILs. Low TILs patients significantly benefited from radiotherapy in reducing IBTR and any recurrence. In luminal B, triple-negative and HER2-positive subtypes, high TILs were associated with better outcomes in DM, OS and DFS. For radiotherapy-treated luminal A breast cancer, low TILs were associated with improved OS. For DCIS patients, low TILs correlated with reduced IBTR. TILs could be a prognostic biomarker for radiotherapy-treated breast cancer patients. However, study heterogeneity complicates comparisons. To refine personalized treatment, further prospective studies are necessary to investigate TILs levels and the impact of neoadjuvant radiotherapy on oncological outcomes across different breast cancer subtypes.
在三阴性和her2阳性乳腺癌中，高肿瘤浸润淋巴细胞（TILs）水平与更好的生存结果相关，突出了其作为预后生物标志物的潜力。放射治疗也能引发免疫细胞浸润。本系统综述评估TILs在放疗乳腺癌患者中的预后价值。文献检索（PubMed， Embase和Web of Science）进行到2024年4月5日（PROSPERO注册号CRD42024401741）。两名独立审稿人根据预先确定的标准筛选文章，通过共识解决差异。收集的结果是TILs对同侧乳腺肿瘤复发（IBTR）、任何复发、远处转移（DM）、总生存期（OS）和无病生存期（DFS）的预后价值。在10927份记录中，纳入了11项研究（3899例患者）。患者接受乳房肿瘤切除术或乳房切除术，术后有或没有放疗。三项研究考察了新辅助部分乳房放疗。高TILs vs低TILs的间质阈值从5%到50%不等，大多数患者（73%）TILs较低。低TILs患者在减少IBTR和任何复发方面明显受益于放疗。在luminal B、三阴性和her2阳性亚型中，高TILs与DM、OS和DFS的较好预后相关。对于放射治疗的腔A乳腺癌，低TILs与改善的OS相关。对于DCIS患者，低TILs与IBTR降低相关。TILs可能是放疗乳腺癌患者的预后生物标志物。然而，研究异质性使比较复杂化。为了完善个性化治疗，需要进一步的前瞻性研究来调查不同乳腺癌亚型的TILs水平和新辅助放疗对肿瘤预后的影响。
{"title":"Prognostic Value of Tumor-Infiltrating Lymphocytes in Breast Cancer Patients Treated With Radiotherapy: A Systematic Review of Literature","authors":"Yasmin A. Civil , Nora D. Purcell , Ralph de Vries , Arlene L. Oei , Victor L.J.L. Thijssen , Tanja D. de Gruijl , Berend J. Slotman , Famke L. Schneiders , H.J.G. Desirée van den Bongard","doi":"10.1016/j.clbc.2025.07.005","DOIUrl":"10.1016/j.clbc.2025.07.005","url":null,"abstract":"<div><div>High tumor-infiltrating lymphocytes (TILs) levels in triple-negative and HER2-positive breast cancer are associated with better survival outcomes, highlighting its potential as prognostic biomarkers. Radiotherapy can also trigger immune cell infiltration. This systematic review evaluates the prognostic value of TILs in radiotherapy-treated breast cancer patients. A literature search (in PubMed, Embase and Web of Science) was performed up to April 5, 2024 (PROSPERO registration CRD42024401741). Two independent reviewers screened articles according to predefined criteria, resolving discrepancies through consensus. The collected outcomes were prognostic value of TILs for ipsilateral breast tumor recurrence (IBTR), any recurrence, distant metastasis (DM), overall survival (OS) and disease-free survival (DFS). Of 10,927 records, 11 studies (3899 patients) were included. Patients underwent lumpectomy or mastectomy, with or without postoperative radiotherapy. Three studies examined neoadjuvant partial breast irradiation. The stroma threshold for high vs. low TILs ranged from 5 to 50%, with most patients (73%) having low TILs. Low TILs patients significantly benefited from radiotherapy in reducing IBTR and any recurrence. In luminal B, triple-negative and HER2-positive subtypes, high TILs were associated with better outcomes in DM, OS and DFS. For radiotherapy-treated luminal A breast cancer, low TILs were associated with improved OS. For DCIS patients, low TILs correlated with reduced IBTR. TILs could be a prognostic biomarker for radiotherapy-treated breast cancer patients. However, study heterogeneity complicates comparisons. To refine personalized treatment, further prospective studies are necessary to investigate TILs levels and the impact of neoadjuvant radiotherapy on oncological outcomes across different breast cancer subtypes.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 165-178.e1"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803723","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.023
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 Junior , Renata Arakelian , Luiz Henrique Gebrim
Purpose
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.
Methods
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.
Results
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).
Conclusion
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.
{"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 Junior , Renata Arakelian , Luiz Henrique Gebrim","doi":"10.1016/j.clbc.2025.07.023","DOIUrl":"10.1016/j.clbc.2025.07.023","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 (<em>P</em> < .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 (<em>P</em> = .002), with the poorest outcomes associated with conversion to HR-/HER-2- (<em>P</em> < .001).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 276-289.e4"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.019
Lisa Anderson , Oindrila Bhattacharyya , Akia Clark , Sharnell Smith , Michael Grimm , Elizabeth Fox , Annie Trance , Bridget A. Oppong
Purpose
With advancements in breast cancer treatment, survivorship has increased, leading to 3.8 million survivors in the US. These women have diverse supportive care needs, often addressed through survivorship programs (SPs), which provide clinical and nonclinical support services. SPs aim to deliver a holistic approach to comprehensive breast cancer treatment and recurrence prevention. Historically, disparities in SP utilization exist among minority and elderly women. This study aims to explore trends varying in SP participation by age and race within a single institution.
Methods
A retrospective analysis of breast cancer patients' survivorship needs at a tertiary referral academic cancer center program was conducted. Data were collected from programs between 2019 and 2022, including demographics and referrals to clinical resources such as Adolescent/Young Adult care, Fertility preservation, Palliative care, Psychosocial support, and Survivorship. Participation in nonclinical areas, including Art, Education, Exercise, Mind-Body-Spirit, and Nutrition, was also evaluated. Descriptive statistics summarized patterns based on age, race, and ethnicity.
Results
From 2019 to 2022, 2198 patients attended SPs, with Nutrition and Exercise being the most popular. Most attendees were 60-69 years old and White. Black attendees declined from 9.9% (2019) to 5.7% (2022). Clinical resources showed the highest referral rate to survivorship clinics. Black patients saw an increase in palliative care referrals, rising from 11% to 21%.
Conclusion
Data reveal differences in clinical referrals by age and race, with fewer referrals for older women and more for Black patients. Participation in nonclinical SPs was similar across groups. Future program development will focus on inclusivity and equitable access.
{"title":"Preferences for Breast Cancer Survivorship Programs Among Multiracial and Ethnic Women","authors":"Lisa Anderson , Oindrila Bhattacharyya , Akia Clark , Sharnell Smith , Michael Grimm , Elizabeth Fox , Annie Trance , Bridget A. Oppong","doi":"10.1016/j.clbc.2025.07.019","DOIUrl":"10.1016/j.clbc.2025.07.019","url":null,"abstract":"<div><h3>Purpose</h3><div>With advancements in breast cancer treatment, survivorship has increased, leading to 3.8 million survivors in the US. These women have diverse supportive care needs, often addressed through survivorship programs (SPs), which provide clinical and nonclinical support services. SPs aim to deliver a holistic approach to comprehensive breast cancer treatment and recurrence prevention. Historically, disparities in SP utilization exist among minority and elderly women. This study aims to explore trends varying in SP participation by age and race within a single institution.</div></div><div><h3>Methods</h3><div>A retrospective analysis of breast cancer patients' survivorship needs at a tertiary referral academic cancer center program was conducted. Data were collected from programs between 2019 and 2022, including demographics and referrals to clinical resources such as Adolescent/Young Adult care, Fertility preservation, Palliative care, Psychosocial support, and Survivorship. Participation in nonclinical areas, including Art, Education, Exercise, Mind-Body-Spirit, and Nutrition, was also evaluated. Descriptive statistics summarized patterns based on age, race, and ethnicity.</div></div><div><h3>Results</h3><div>From 2019 to 2022, 2198 patients attended SPs, with Nutrition and Exercise being the most popular. Most attendees were 60-69 years old and White. Black attendees declined from 9.9% (2019) to 5.7% (2022). Clinical resources showed the highest referral rate to survivorship clinics. Black patients saw an increase in palliative care referrals, rising from 11% to 21%.</div></div><div><h3>Conclusion</h3><div>Data reveal differences in clinical referrals by age and race, with fewer referrals for older women and more for Black patients. Participation in nonclinical SPs was similar across groups. Future program development will focus on inclusivity and equitable access.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 247-253"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945006","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.07.017
Francisco Cezar Aquino de Moraes , Pedro Henrique de Souza Wagner , Ana Beatriz Nardelli da Silva , Maria Cristina Figueroa Magalhães , Rommel Mario Rodríguez Burbano
Introduction
Breast cancer (BC) is the most common cancer among women worldwide, accounting for over 2.3 million new cases annually. Recent evidence suggests Epstein-Barr virus (EBV) may play a role in its pathogenesis. Given EBV’s known oncogenic potential, this study investigates the prevalence and possible role of EBV in BC pathogenesis.
Methods
Random-effects meta-analyses were conducted to estimate raw proportions and risk ratio (RR), with 95% confidence intervals (CIs). Heterogeneity was assessed using I². Statistical significance was set at P < .05. Analyses were performed in R 4.2.3
Results
Our meta-analysis included 57 studies, comprising a total of 5,133 BC tissues to analyze the presence of EBV. Our analysis revealed a prevalence of 25% (95% CI: 21%-30%) of EBV in BC tissues. In the analysis by continent, Europe, Africa, and Oceania showed a similar proportion of 33%. Regarding the risk of EBV in BC tissues compared to healthy controls, the analysis identified a statistically significant difference, presenting higher risk of EBV in the BC group (RR: 3.35; P < .001). South America showed the highest and significant RR of 12.34 (P = .007) among the continents. Subgroup analysis by income revealed that the low-income-group exhibited the highest EBV prevalence (44%; 95% CI: 28%-61%). According to the subtype BC analysis, triple-negative BC exhibited the highest EBV prevalence (30%; 95% CI: 19%-44%).
Conclusion
This meta-analysis underscores the global prevalence of EBV in BC and highlights a potential association between EBV presence and breast cancer. Further standardized, prospective studies using robust detection methods, including paired tissue analyses, are needed to confirm these observations and to clarify the possible role of EBV in breast tumorigenesis.
{"title":"Does Epstein–Barr Virus Contribute to Breast Cancer Risk Worldwide? A Systematic Review and Meta-Analysis","authors":"Francisco Cezar Aquino de Moraes , Pedro Henrique de Souza Wagner , Ana Beatriz Nardelli da Silva , Maria Cristina Figueroa Magalhães , Rommel Mario Rodríguez Burbano","doi":"10.1016/j.clbc.2025.07.017","DOIUrl":"10.1016/j.clbc.2025.07.017","url":null,"abstract":"<div><h3>Introduction</h3><div>Breast cancer (BC) is the most common cancer among women worldwide, accounting for over 2.3 million new cases annually. Recent evidence suggests Epstein-Barr virus (EBV) may play a role in its pathogenesis. Given EBV’s known oncogenic potential, this study investigates the prevalence and possible role of EBV in BC pathogenesis.</div></div><div><h3>Methods</h3><div>Random-effects meta-analyses were conducted to estimate raw proportions and risk ratio (RR), with 95% confidence intervals (CIs). Heterogeneity was assessed using I². Statistical significance was set at <em>P</em> < .05. Analyses were performed in R 4.2.3</div></div><div><h3>Results</h3><div>Our meta-analysis included 57 studies, comprising a total of 5,133 BC tissues to analyze the presence of EBV. Our analysis revealed a prevalence of 25% (95% CI: 21%-30%) of EBV in BC tissues. In the analysis by continent, Europe, Africa, and Oceania showed a similar proportion of 33%. Regarding the risk of EBV in BC tissues compared to healthy controls, the analysis identified a statistically significant difference, presenting higher risk of EBV in the BC group (RR: 3.35; <em>P</em> < .001). South America showed the highest and significant RR of 12.34 (<em>P</em> = .007) among the continents. Subgroup analysis by income revealed that the low-income-group exhibited the highest EBV prevalence (44%; 95% CI: 28%-61%). According to the subtype BC analysis, triple-negative BC exhibited the highest EBV prevalence (30%; 95% CI: 19%-44%).</div></div><div><h3>Conclusion</h3><div>This meta-analysis underscores the global prevalence of EBV in BC and highlights a potential association between EBV presence and breast cancer. Further standardized, prospective studies using robust detection methods, including paired tissue analyses, are needed to confirm these observations and to clarify the possible role of EBV in breast tumorigenesis.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 229-246.e22"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944992","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.08.008
Israa K. Mohamed , Maggie M. Abbassi , Mohamed R. Kelany , Samar F. Farid
Aim
The purpose of this study is to compare topical betamethasone-17-valerate and olive oil cream in preventing radiation-induced dermatitis (RID) in breast cancer patients and to provide prospective data evaluating the quality of life, subjective symptoms, and treatment satisfaction reported by the patients.
Methods
This was a prospective, double-blind, randomized, parallel, placebo-controlled trial. A total of 132 patients were randomized into three groups to receive either olive oil cream (G1), betamethasone-17-valerate (Betnovate® cream, GlaxoSmithKline) (G2), or unmedicated cream base (G3) throughout radiotherapy (RT) and 2 weeks after. The study is registered on clinicaltrials.gov with ID: NCT05285943, Date: November 2021.
Results
A total of 128 patients were included in the final analysis. Betamethasone and olive oil significantly differed from the unmedicated cream base at weeks 1 to 4 (P < 0.05). At week 5, only significance was observed between olive oil and unmedicated cream base (P = 0.013), and the mean RTOG (Radiation Therapy Oncology Group) score was significantly lower in olive oil and betamethasone groups than in the unmedicated cream base group (P < 0.05 at weeks 1-5) but, there was no significant difference between olive oil and betamethasone (P > 0.999). Furthermore, the percentage of patients who developed grade 3 at the end of the follow-up was significantly different between the olive oil group and the unmedicated cream base group (27.9% vs. 61%, P = 0.004). Additionally, olive oil and betamethasone had non-significant delayed grade 2 and grade 3 development (P > 0.999).
Conclusion
Olive oil cream is as effective as betamethasone in alleviating RID in patients treated with adjuvant radiotherapy for breast cancer.
{"title":"Efficacy of Topical Betamethasone Valerate and Olive Oil in Preventing Acute Radiation Dermatitis in Breast Cancer: A Randomized Double-Blind Placebo-Controlled Study","authors":"Israa K. Mohamed , Maggie M. Abbassi , Mohamed R. Kelany , Samar F. Farid","doi":"10.1016/j.clbc.2025.08.008","DOIUrl":"10.1016/j.clbc.2025.08.008","url":null,"abstract":"<div><h3>Aim</h3><div>The purpose of this study is to compare topical betamethasone-17-valerate and olive oil cream in preventing radiation-induced dermatitis (RID) in breast cancer patients and to provide prospective data evaluating the quality of life, subjective symptoms, and treatment satisfaction reported by the patients.</div></div><div><h3>Methods</h3><div>This was a prospective, double-blind, randomized, parallel, placebo-controlled trial. A total of 132 patients were randomized into three groups to receive either olive oil cream (G1), betamethasone-17-valerate (Betnovate® cream, GlaxoSmithKline) (G2), or unmedicated cream base (G3) throughout radiotherapy (RT) and 2 weeks after. The study is registered on clinicaltrials.gov with ID: NCT05285943, Date: November 2021.</div></div><div><h3>Results</h3><div>A total of 128 patients were included in the final analysis. Betamethasone and olive oil significantly differed from the unmedicated cream base at weeks 1 to 4 (<em>P</em> < 0.05). At week 5, only significance was observed between olive oil and unmedicated cream base (<em>P</em> = 0.013), and the mean RTOG (Radiation Therapy Oncology Group) score was significantly lower in olive oil and betamethasone groups than in the unmedicated cream base group (<em>P</em> < 0.05 at weeks 1-5) but, there was no significant difference between olive oil and betamethasone (<em>P</em> > 0.999). Furthermore, the percentage of patients who developed grade 3 at the end of the follow-up was significantly different between the olive oil group and the unmedicated cream base group (27.9% vs. 61%, <em>P</em> = 0.004). Additionally, olive oil and betamethasone had non-significant delayed grade 2 and grade 3 development (<em>P</em> > 0.999).</div></div><div><h3>Conclusion</h3><div>Olive oil cream is as effective as betamethasone in alleviating RID in patients treated with adjuvant radiotherapy for breast cancer.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 348-359.e1"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091266","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}
Pub Date : 2026-01-01DOI: 10.1016/j.clbc.2025.08.004
Mohammed Dlshad Mohsin , Abbas Salihi
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 (H2O2), 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.
{"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":"10.1016/j.clbc.2025.08.004","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":"26 1","pages":"Pages 330-345"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","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}
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