Breast Cancer Research最新文献

{"title":"DNA methylation-predicted plasma protein levels and breast cancer risk.","authors":"Jacob K Kresovich, Brett M Reid, Katie M O'Brien, Zongli Xu, Doratha A Byrd, Clarice R Weinberg, Dale P Sandler, Jack A Taylor","doi":"10.1186/s13058-025-02004-x","DOIUrl":"10.1186/s13058-025-02004-x","url":null,"abstract":"<p><strong>Background: </strong>Blood DNA methylation (DNAm) profiles have been used to show that changes in circulating leukocyte composition occur during breast cancer development, suggesting that peripheral immune system alterations are markers of breast cancer risk. Blood DNAm profiles have recently been used to predict plasma protein concentrations (\"Protein EpiScores\"), but their associations with breast cancer risk have not been examined in detail.</p><p><strong>Methods: </strong>Whole blood DNAm profiles were obtained for a case-cohort sample of participants in the Sister Study and used to calculate 109 Protein EpiScores. Of the 4,479 women included, 2,151 (48%) were diagnosed with breast cancer within 15 years of their baseline blood draw (median time to diagnosis: 8.6 years; 1,673 invasive cancer and 478 ductal carcinomas in situ). Protein EpiScores associations with breast cancer incidence were estimated using weighted Cox regression models, overall and stratified by time and participant characteristics.</p><p><strong>Results: </strong>Protein EpiScores for RARRES2, IGFBP4, and CCL21 were positively associated with invasive breast cancer risk (hazard ratios from 1.17 to 1.24), while those for F7, SELL, CXCL9, CD48, and IL19 were inversely associated (hazard ratios from 0.82 to 0.86) (all FDR < 0.10). Eight immune response-related Protein EpiScores (CXCL9, CD48, FCGR3B, CXCL11, CCL21, CRTAM, VCAM1, GZMA) were associated with invasive cancers diagnosed within five years of enrollment. Protein EpiScore associations were consistently stronger for estrogen receptor-negative tumors.</p><p><strong>Conclusions: </strong>Several Protein EpiScores, including many related to immune response, were associated with breast cancer risk, highlighting novel changes to the peripheral immune system that occur during breast cancer development.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"46"},"PeriodicalIF":7.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China.","authors":"Hong Lv, Junqiu Yue, Qingfu Zhang, Fangping Xu, Peng Gao, Haifeng Yang, Xiu Nie, Lingfei Kong, Guanjun Zhang, Jianming Li, Shiwei Xiao, Hongmei Wu, Aiyan Xing, Min Hong, Jun Fan, Huijuan Guan, Peilong Cao, Hengli Ni, Wentao Yang","doi":"10.1186/s13058-025-02001-0","DOIUrl":"10.1186/s13058-025-02001-0","url":null,"abstract":"<p><strong>Background: </strong>Accurately assessing HER2-low (immunohistochemistry [IHC] 1 + and IHC 2+/in situ hybridization [ISH]-) and HER2-ultralow (IHC > 0 < 1+) is essential given the emergence of novel therapies. Thorough understanding of the reproducibility of rescoring IHC stained slides or re-staining archived tissue slides is essential.</p><p><strong>Methods: </strong>2,869 breast cancer patients diagnosed between July 2021 and July 2022 from 10 hospitals in China were included in this multicentre study. The prevalence of different HER2 expression levels and distribution of HER2 IHC scores were assessed by HER2 status determination from rescored historical slides. Concordance was evaluated across historical results versus rescored results, historical results versus re-stained results, and leading center results versus local site results. Clinicopathological characteristics were retrospectively analyzed as well.</p><p><strong>Results: </strong>HER2 IHC 0, IHC 1+, IHC 2+, and IHC 3 + were identified in 682 (23.8%), 871 (30.4%), 801 (27.9%), and 515 (18.0%) cases, respectively. HER2-positive, HER2-low, and HER2 IHC 0 (HER2-ultralow and IHC null) were identified in 21.7%, 54.5%, and 23.8% of cases, respectively. The prevalence of HER2-ultralow and IHC null was 10.6% and 13.2%, respectively. The concordance for HER2-ultralow was 43.3%; 30% of cases that were scored as HER2-ultralow at local sites were rescored as HER2-null and 26.7% of cases were rescored as IHC 1 + at the leading site. Overall, there was substantial agreement (83.1%) between rescored and historical IHC results. A high concordance rate of 91.7% was observed for HER2-low classification.</p><p><strong>Conclusions: </strong>This is the first multicenter study to determine the prevalence of HER2-low and HER2-ultralow based on rescored results in the Chinese breast cancer population. The concordance analysis carries important implications for the diagnosis of HER2-low and HER2-ultralow cases in clinical practice. The relatively low concordance in identifying HER2-ultralow suggested that the reproducibility of scoring HER2-ultralow needed to be improved through training.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT05203458.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"45"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary measures show that recurrence of DCIS is distinct from progression to breast cancer.","authors":"Angelo Fortunato, Diego Mallo, Luis Cisneros, Lorraine M King, Aziz Khan, Christina Curtis, Marc D Ryser, Joseph Y Lo, Allison Hall, Jeffrey R Marks, E Shelley Hwang, Carlo C Maley","doi":"10.1186/s13058-025-01966-2","DOIUrl":"10.1186/s13058-025-01966-2","url":null,"abstract":"<p><strong>Background: </strong>Progression from pre-cancers like ductal carcinoma in situ (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity would predict clinical outcomes for DCIS since it serves as the substrate for natural selection among cells.</p><p><strong>Methods: </strong>We profiled two samples from two geographically distinct foci from each DCIS in both cross-sectional (n = 119) and longitudinal cohorts (n = 224), with whole exome sequencing, low-pass whole genome sequencing, and a panel of immunohistochemical markers.</p><p><strong>Results: </strong>In the longitudinal cohorts, the only statistically significant associations with time to non-invasive DCIS recurrence were the combination of treatment (lumpectomy only vs mastectomy or lumpectomy with radiation, HR 12.13, p = 0.003, Wald test with FDR correction), ER status (HR 0.16 for ER+ compared to ER-, p = 0.0045), and divergence in SNVs between the two samples (HR 1.33 per 10% divergence, p = 0.018). SNV divergence also distinguished between pure DCIS and DCIS synchronous with invasive disease in the cross-sectional cohort. In contrast, the only statistically significant associations with time to progression to invasive disease were the combination of the width of the surgical margin (HR 0.67 per mm, p = 0.043) and the number of mutations that were detectable at high allele frequencies (HR 1.30 per 10 SNVs, p = 0.02). No predictors were significantly associated with both DCIS recurrence and progression to invasive disease, suggesting that the evolutionary scenarios that lead to these clinical outcomes are markedly different.</p><p><strong>Conclusions: </strong>These results imply that recurrence with DCIS is a clinical and biological process different from invasive progression.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"43"},"PeriodicalIF":7.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cells and energy metabolism in HER2-positive DCIS: insights into breast cancer progression from spatial-omics analyses.","authors":"Helga Bergholtz, Jens Henrik Norum, Tonje Gulbrandsen Lien, Martina Landschoof Skrede, Øystein Garred, Therese Sørlie","doi":"10.1186/s13058-025-01990-2","DOIUrl":"10.1186/s13058-025-01990-2","url":null,"abstract":"<p><p>During breast tumor progression, the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer is a critical step with large implications for prognosis. However, the mechanisms of invasion are still largely unknown. At the DCIS stage, there is an over-representation of HER2-positive lesions compared with invasive breast cancer. In this study, we investigated the associations between gene expression profiles in cancer cells and the immune microenvironment of HER2-positive DCIS and invasive breast tumors with concurrent DCIS using spatial transcriptomics. We found distinctly more B cells in the vicinity of DCIS ducts than in invasive tumor areas. There was higher expression of genes involved in energy metabolism in DCIS cancer cells than in invasive cancer cells and a positive correlation between expression of metabolic genes and B-cell abundance in DCIS. In contrast were processes related to epithelial to mesenchymal transition negatively correlated with B-cell abundance in DCIS. We also found significant correlation between expression of the B-cell-attracting chemokines CCL19, CCL21 and CXCL13 in stromal cells and B cell abundance in DCIS. This study indicates that B cells may play a protective role in the progression of HER2-positive DCIS to invasive breast cancer and that increased metabolic activity in intraductal cancer cells in combination with chemokines produced by stromal cells may influence the immune microenvironment of DCIS. These findings have implications for understanding HER2-positive breast cancer progression.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"44"},"PeriodicalIF":7.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant chemotherapy response in androgen receptor-positive triple-negative breast cancer: potential predictive biomarkers and genetic alterations.","authors":"Ming Li, Shuling Zhou, Hong Lv, Mengyuan Cai, Ruohong Shui, Wentao Yang","doi":"10.1186/s13058-025-01994-y","DOIUrl":"10.1186/s13058-025-01994-y","url":null,"abstract":"<p><strong>Background: </strong>The aim of the present study was to investigate whether the androgen receptor (AR) status affects the efficacy of neoadjuvant chemotherapy (NACT) in triple negative breast cancer (TNBC) patients, and to elucidate the predictive biomarkers and mutations associated with pathological complete response (pCR) in AR-positive TNBC patients.</p><p><strong>Methods: </strong>The current retrospective cohort included 226 TNBC patients who underwent NACT. AR and FOXC1 were assessed by immunohistochemistry on pretreatment biopsy specimens of 226 TNBC patients from 2018 to 2022. The clinicopathological features of AR-negative, AR < 10%, and AR ≥ 10% TNBC patients were analyzed to confirm the appropriate threshold. The response was evaluated in terms of pCR and Miller-Payne (MP) grade in the subsequent mastectomy or breast conservation samples. Next-generation sequencing (NGS) was utilized to further investigate the molecular characteristics of 44 AR-positive TNBC patients.</p><p><strong>Results: </strong>Among the 226 TNBC patients, compared with AR-negative and AR < 10% tumors (68.58%, 155/226), AR ≥ 10% TNBC patients (31.41%, 71/226) exhibited distinct clinicopathological features, while no significant difference was detected between those with AR-negative tumors and those with AR < 10% tumors. Thus, tumors with AR ≥ 10% expression were defined as having AR positive expression. The pCR rate of AR-positive TNBCs was lower than that of AR-negative TNBC patients (12.68% vs. 34.19%, p < 0.001). In TNBC, multivariate analysis demonstrated that FOXC1 was an independent predictor of pCR (p = 0.042), whereas AR was not. The pCR rate was higher in FOXC1 positive patients than in FOXC1 negative patients (34.44% vs. 3.13%, p < 0.001). In the AR-positive TNBC subgroup, patients with FOXC1 expression had lower AR expression, higher Ki-67 expression, and higher histological grade. Compared with AR-positive TNBC patients who achieved pCR, the non-pCR patients had a greater percentage of mutations in genes involved in the PI3K/AKT/mTOR pathway.</p><p><strong>Conclusions: </strong>The current study indicated that the AR-positive TNBC is correlated with lower rates of pCR after NACT. The expression of FOXC1 in TNBC patients and AR-positive TNBC patients could be utilized as a predictive marker for the efficacy of NACT. The present study provides a rationale for treating these non-pCR AR-positive TNBC tumors with PI3K/AKT/mTOR inhibitors.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"41"},"PeriodicalIF":7.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological complete response, histologic grade, and level of stromal tumor-infiltrating lymphocytes in ER + HER2- breast cancer.","authors":"Seung Ho Baek, Min Ji Lee, Yoonwon Kook, Soong June Bae, Joon Jeong, Yoon Jin Cha, Sung Gwe Ahn","doi":"10.1186/s13058-025-01999-7","DOIUrl":"10.1186/s13058-025-01999-7","url":null,"abstract":"<p><strong>Background: </strong>Recent trials have integrated immune checkpoint inhibitors (ICIs) into neoadjuvant chemotherapy (NAC) in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer of histologic grade (HG) III. We assessed the pathological complete response (pCR) rate according to the level of stromal tumor-infiltrating lymphocytes (sTIL) and HG in patients with ER + HER2- breast cancer undergoing NAC.</p><p><strong>Methods: </strong>Between January 2016 and December 2023, we retrospectively identified 376 patients with ER + HER2- breast cancer who underwent NAC followed by surgery. HG and sTIL levels were examined in the biopsied samples before NAC. Multiple sTIL cutoff values as 10%, 20%, and 30% were applied.</p><p><strong>Results: </strong>Twenty-seven patients (7.2%) had HG III tumors. The pCR rate in the HG III group was 22.2%, which was significantly higher than that in the HG I/II group (4.0%) (p < 0.001). The HG III group had a higher mean sTIL level than HG I/II group (38.7% vs. 12.9%; p < 0.001). According to the sTIL levels, the pCR rate in the high sTIL group was significantly higher than that in the low sTIL group: i) cutoff of 10%, 2.4% vs. 9.5%; cutoff of 20%, 2.8% vs. 13.7%; and cutoff of 30%, 3.2% vs. 18.3%. In the high sTIL (≥ 30%) group, the pCR rate for HG III was 33.3%, whereas that for HG I/II was 13.3%.</p><p><strong>Conclusions: </strong>High tumor grade and sTIL levels were associated with higher rates of pCR in ER + HER2- breast cancer. Our findings support that the addition to ICIs to NAC increased pCR in high-risk, HG III, ER + HER2- breast cancer and suggest that sTIL levels could be utilized to identify patients with ER + HER2- breast cancer eligible for chemoimmunotherapy.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"42"},"PeriodicalIF":7.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone.","authors":"James N Ingle, Vera J Suman, Malvika H Solanki, Marie R Passow, Jordan D Campbell, Liewei Wang, Matthew P Goetz","doi":"10.1186/s13058-025-01992-0","DOIUrl":"10.1186/s13058-025-01992-0","url":null,"abstract":"<p><strong>Background: </strong>Our goal was to evaluate the impact of level of androgen receptor (AR) expression on outcomes in women with estrogen receptor α (ER) positive breast cancer. We sought to corroborate our preclinical findings that AR-agonists were efficacious in patients with ER-positive tumors that also expressed high levels of AR.</p><p><strong>Methods: </strong>Tissue microarrays (TMAs) were prepared from primary tumor blocks from patients entered on a prospective randomized adjuvant trial of tamoxifen (Tam) alone or combined with fluoxymesterone (Flu), an AR-agonist, (NCCTG 89-30-52). TMAs were stained for ER and AR and expression examined in decile increments (0-100%) of positive invasive tumor nuclei. The primary endpoint was relapse-free survival (RFS).</p><p><strong>Results: </strong>301 (59%) of the 514 patients had sufficient tissue to determine ER and AR expression, where nuclear staining of > 70% was considered \"enriched\" and nuclear staining of ≤ 70% was considered \"poor/moderate\". Eleven (4%) of these patients had poor/moderate ER staining and were excluded from these analyses. The proportion of the ER-enriched tumors that also had AR-enriched expression levels was 56.3% in the Tam arm and 51.8% in the Tam + Flu arm. Within the AR-enriched patients, the cumulative incidence of RFS events showed an advantage for Tam + Flu over Tam alone that reached significance (Gray's test p = 0.0472).</p><p><strong>Conclusions: </strong>Our findings suggest that an AR-agonist may be of value in AR-enriched, ER-enriched breast cancers and should be studied in future trials because of the availability of new, more tolerable AR-agonists.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"40"},"PeriodicalIF":7.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathologic response rates in HER2-low versus HER2-zero early breast cancer patients receiving neoadjuvant therapy: a systematic review and meta-analysis.","authors":"Francisco Cezar Aquino de Moraes, Caio Henrique Duarte de Castro Ribeiro, Felipe Dircêu Dantas Leite Pessôa, Juliana Ramos Chaves, Ana Paula Borges de Souza, Diego Di Felipe Ávila Alcantara, Margareth Maria Braun Guimarães Imbiriba, Maria Cristina Figueroa Magalhães, Rommel Mario Rodríguez Burbano","doi":"10.1186/s13058-025-01989-9","DOIUrl":"10.1186/s13058-025-01989-9","url":null,"abstract":"<p><strong>Background: </strong>Currently, the primary methods for detecting HER2 expression levels are immunohistochemistry (IHC) and in situ hybridization (ISH), with the traditional standard being a HER2-positive score of 3 + accompanied by ERBB2 gene amplification detected through ISH. However, a new entity has recently emerged: HER2-low, defined as HER2 IHC 1 + or 2 + with negative ISH. HER2-low breast cancer, representing 45-60% of all HER2-negative tumors, has distinct biological characteristics and uncertain responses to conventional HER2-targeted therapies. Recent studies suggest varied clinical outcomes, highlighting the need for further investigation into the impact of HER2-low status on treatment efficacy and prognosis.</p><p><strong>Objective: </strong>This meta-analysis evaluates the difference in complete pathological response (pCR), disease-free survival (DFS), and overall survival (OS) between HER2-low and HER2-zero phenotypes.</p><p><strong>Methods: </strong>We systematically searched the main databases PubMed, Scopus, and Web of Science for articles evaluating women in neoadjuvant therapy expressing HER2-low and HER2-zero. We computed odds ratios (ORs) or hazard ratios (HRs) using DerSimonian and Laird random-effect models for all endpoints, with 95% confidence intervals (CIs). We assessed the heterogeneity using I² statistics. R, version 4.2.3, was used for statistical analyses.</p><p><strong>Results: </strong>38 studies totaling 70,104 patients were included. The HER2-low group accounted for 61.3% of patients while HR + status represented 52.4% in the whole research. In 67,839 women, the pCR was analyzed, which in the overall cohort analysis favored the HER2-zero group (OR 0.84; 95% CI 0.78-0.90; p = 0.000005; I² = 15%). Subgroup analyses for triple-negative breast cancer (TNBC) and HR + patients also favored HER2-zero expression, with an OR of 0.91 (95% CI 0.83-1.0; p < 0.041; I² = 12%) and 0.75 (95% CI 0.70-0.81; p < 0.000001; I² = 0%), respectively. In the multivariate analysis across all patients, both DFS and OS outcomes were significantly favorable for the HER2-low expression group, with HR 0.8317 (95% CI 0.7036-0.9832; p = 0.031) for DFS and HR 0.806 (95% CI 0.663-0.979; p = 0.03) for OS.</p><p><strong>Conclusion: </strong>Based on our findings, HER2-zero status is associated with a significantly higher pathological complete response (pCR) rate compared to HER2-low in early-stage breast cancer, and other survival outcomes. These results suggest that HER2-zero should be considered a prognostic factor in early-stage breast cancer and taken into account in neoadjuvant treatment planning and future clinical research.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"39"},"PeriodicalIF":7.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis.","authors":"Diana Zhang, Shayesteh Jahanfar, Judy B Rabinowitz, Joshua Dower, Fei Song, Cherng-Horng Wu, Xiao Hu, Phillip Tracy, Mark Basik, Arielle Medford, Po-Han Lin, Chiun-Sheng Huang, Francois-Clement Bidard, Shufang Renault, Lori Pai, Mary Buss, Heather A Parsons, Ilana Schlam","doi":"10.1186/s13058-025-01986-y","DOIUrl":"10.1186/s13058-025-01986-y","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and carries a worse prognosis relative to other breast cancer subtypes. This systematic review and meta-analysis evaluated the prognostic value of circulating tumor DNA (ctDNA) in early-stage TNBC.</p><p><strong>Methods: </strong>A literature search was conducted using Ovid Medline, Elsevier EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science Databases for publications up to 11/16/2023. Results were uploaded to Covidence and assessed by two independent reviewers. Studies assessing the use of ctDNA to predict recurrence free survival and related outcomes as well as overall survival were included. All recurrence outcomes were combined during analysis. Statistical analysis was performed using Revman Web. Log-hazard ratios (HR) were pooled for studies reporting recurrence and death as a time-to-event outcomes. Odds ratios (OR) were calculated and pooled for studies reporting patient-level data on recurrence, death, and pathological complete response (pCR). Prospero ID: CRD42023492529.</p><p><strong>Results: </strong>A total of 3,526 publications were identified through our literature search, and 20 publications (n = 1202 patients) were included in the meta-analysis. In studies that reported recurrence as a time-to-event outcome, post-neoadjuvant (before or after surgery) ctDNA + status was associated with a higher likelihood of disease recurrence (HR 4.12, 95% confidence interval [CI] 2.81-6.04). For studies that reported patient-level data, post-neoadjuvant ctDNA + status was associated with higher odds of disease recurrence (OR 6.72, 95% CI 3.61-12.54). Pooled log-HR also revealed that ctDNA + status in the post-neoadjuvant setting (before or after surgery) was associated with worse overall survival (HR 3.26, 95% CI 1.88-5.63).</p><p><strong>Conclusions: </strong>Our findings suggest that ctDNA could be used as a prognostic biomarker to anticipate the risk of relapse. However, it remains unclear if therapeutic intervention for patients who are ctDNA + can improve outcomes. While more studies are needed before incorporating ctDNA into clinical practice, the findings of this meta-analysis are reassuring and show the promise of ctDNA as a biomarker.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"38"},"PeriodicalIF":7.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular determinants of response to neoadjuvant pembrolizumab plus chemotherapy in patients with high-risk, early-stage, triple-negative breast cancer: exploratory analysis of the open-label, multicohort phase 1b KEYNOTE-173 study.","authors":"Rebecca Dent, Javier Cortés, Yeon Hee Park, Eva Muñoz-Couselo, Sung-Bae Kim, Joohyuk Sohn, Seock-Ah Im, Esther Holgado, Theodoros Foukakis, Sherko Kümmel, Jennifer Yearley, Anran Wang, Michael Nebozhyn, Lingkang Huang, Razvan Cristescu, Petar Jelinic, Vassiliki Karantza, Peter Schmid","doi":"10.1186/s13058-024-01946-y","DOIUrl":"10.1186/s13058-024-01946-y","url":null,"abstract":"<p><strong>Background: </strong>The multicohort, open-label, phase 1b KEYNOTE-173 study was conducted to investigate pembrolizumab plus chemotherapy as neoadjuvant therapy for triple-negative breast cancer (TNBC). This exploratory analysis evaluated features of the tumor microenvironment that might be predictive of response.</p><p><strong>Methods: </strong>Cell fractions from 20 paired samples collected at baseline and after one cycle of neoadjuvant pembrolizumab prior to chemotherapy initiation were analyzed by spatial localization (tumor compartment, stromal compartment, or sum of tumor and stromal compartments [total tumor]) using three six-plex immunohistochemistry panels with T-cell, myeloid cell, and natural killer cell components. Area under the receiver operating characteristic curve (AUROC) was used to assess associations between immune subsets and gene expression signatures (T-cell-inflamed gene expression profile [Tcell_infGEP] and 10 non-Tcell_infGEP signatures using RNA sequencing) and pathologic complete response (pCR).</p><p><strong>Results: </strong>At baseline, six immune subsets quantitated within the tumor compartment showed AUROC with 95% CIs not crossing 0.5, including CD11c⁺ cells (macrophage and dendritic cell [DC]: AUROC, 0.85; 95% confidence interval [CI] 0.63-1.00), CD11c⁺/MHCII⁺/CD163^-/CD68^- cells (DC: 0.76; 95% CI, 0.53-0.99), CD11c⁺/MHCII^-/CD163^-/CD68^- cells (nonactivated/immature DC: 0.80; 95% CI 0.54-1.00), and CD11c⁺/CD163⁺ cells (M2 macrophage: 0.77; 95% CI 0.55-0.99). Other associations with pCR included baseline CD11c⁺/MHCII^-/CD163^-/CD68^- (nonactivated/immature DC) within the total tumor (AUROC, 0.76; 95% CI 0.51-1.00) and the baseline CD11c/CD3 ratio within the tumor compartment (0.75; 95% CI 0.52-0.98). Changes in immune subsets following one cycle of pembrolizumab were not strongly associated with pCR. Although T-cell associations were relatively weak, specific CD8 subsets trended toward association. The AUROC for discriminating pCR based on Tcell_infGEP was 0.55 (95% CI 0.25-0.85); when detrended by Tcell_infGEP, AUROC varied for the non-Tcell_infGEP signatures. Tcell_infGEP expression trended higher in responders than in nonresponders when evaluating pCR.</p><p><strong>Conclusions: </strong>Myeloid cell populations within the tumor compartment at baseline and Tcell_infGEP show a promising trend toward an association with pCR in a small subgroup of patients with early-stage TNBC treated with neoadjuvant pembrolizumab plus chemotherapy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT02622074; registration date, December 2, 2015.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"35"},"PeriodicalIF":7.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}