Breast Cancer Research最新文献

{"title":"A comparative study of four cell-free DNA assays for detecting circulating tumor DNA in early breast cancer.","authors":"Charlotta V Mulder, Elisabeth M Jongbloed, Marte C Liefaard, Stavros Makrodimitris, Daan M Hazelaar, Corine M Beaufort, Vanja de Weerd, Lennart Mulder, Carolien H M van Deurzen, Gabe S Sonke, Agnes Jager, Saskia M Wilting, John W M Martens, Maurice P H M Jansen, Esther H Lips","doi":"10.1186/s13058-025-02077-8","DOIUrl":"10.1186/s13058-025-02077-8","url":null,"abstract":"<p><p>Early prediction of the response to neoadjuvant chemotherapy (NAC) enables tailoring treatment strategies to the specific needs of individual breast cancer patients. Circulating tumor DNA (ctDNA) has shown to be a prognostic factor for response on NAC during treatment. However, at this point in time mostly tumor-informed ctDNA detection methods are used which are costly, have relatively long turnaround times and are subsequently potentially less feasible for widespread clinical application. In this study, we investigated four tumor-agnostic methods to determine their ability to accurately detect circulating tumor DNA (ctDNA) at baseline. These methods were the Oncomine Breast cell free DNA (cfDNA) NGS panel, the LINE-1 sequencing assay mFAST-SeqS, shallow whole genome sequencing and the genome-wide methylation profiling assay MeD-Seq. In total 40 patients with triple negative or luminal B breast cancer were included and cell free DNA (cfDNA) from plasma before the start of NAC was analyzed with the four assays. We detected ctDNA in 3/24 (12.5%) patients with Oncomine, 5/40 (12.5%) with mFast-SeqS, 3/40 (7.7%) with low pass shallow WGS and 23/40 with MeD-Seq (57.5%). When all methods were combined ctDNA was detected in 65% of patients. In conclusion, we demonstrated that tumor agnostic methods, in particular MeD-Seq, can detect ctDNA in a fraction of the patients with early breast cancer, but further optimization is needed to reach the potential currently demonstrated by tumor-informed methods.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"120"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545791","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":"Long-term weight change among breast cancer patients treated with chemotherapy: a longitudinal study over 13 years.","authors":"Mathilde His, Iris Baggio, Sylvie Chabaud, Louis Tassy, Olivier Trédan, Béatrice Fervers, Olivia Pérol","doi":"10.1186/s13058-025-02079-6","DOIUrl":"10.1186/s13058-025-02079-6","url":null,"abstract":"<p><strong>Background: </strong>Weight gain during chemotherapy is frequently reported in breast cancer patients and adversely impacts survival and quality of life. However, weight change over the long term and its determinants in breast cancer patients who received chemotherapy remain unclear. This study aimed to characterize weight change over 13 years among French breast cancer patients diagnosed with early-stage breast cancer who received adjuvant chemotherapy.</p><p><strong>Methods: </strong>We examined weight change over 13 years in a cohort of 267 early breast cancer patients diagnosed between 2004 and 2006 and treated with adjuvant chemotherapy. Yearly weight measures were obtained from medical records, or from questionnaires when not available from medical records. We compared weight at each time using analysis of variance for repeated data based on mixed-effect models, and examined clinical and individual factors as potential determinants of weight change over the study period.</p><p><strong>Results: </strong>More than one third of women experienced weight gain > 5% of their initial body weight following initiation of adjuvant chemotherapy (34.6%, 36.0%, 41.6%, and 37.4% at years 1, 5, 10, 13, respectively). A statistically significant weight gain occurred during the first year after initiation of chemotherapy (estimated mean gain: 1.80 kg; 95% confidence interval (0.52-3.1) kg) and was maintained for up to 13 years (P-value for overall effect of time on weight < 0.001). This weight gain was observed only for women with an initial BMI < 25 kg/m². Type of chemotherapy, use of hormone therapy, age at inclusion, menopausal status, or physical activity level at initial visit did not show statistically significant association with weight change.</p><p><strong>Conclusions: </strong>These results emphasize the need to improve our understanding of weight change and its determinants and to develop effective intervention strategies to prevent weight gain for breast cancer patients during the first year of treatment.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"117"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545793","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":"Medications to reduce breast cancer risk: a network meta-analysis of randomized controlled trials.","authors":"Ghazaleh Pourali, Minglu Liu, Supriya S Sherpa, Angela Hardi, Chongliang Luo, Adetunji T Toriola","doi":"10.1186/s13058-025-02059-w","DOIUrl":"10.1186/s13058-025-02059-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Given the rising incidence of breast cancer, especially in premenopausal women, there is an urgent need to identify additional risk-reducing medications to accelerate prevention, as only a few are currently approved. We, therefore, performed network meta-analysis (NMA) to identify and compare the efficacy of medications for primary breast cancer prevention.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a literature search completed on November 16, 2023, in Embase, Ovid-Medline, Scopus, and Cochrane Library for randomized controlled trials (RCTs) evaluating risk-reducing medications in women without a history of invasive breast cancer. Two reviewers independently screened and extracted data based on predefined criteria, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and assessed the risk of bias using the Revised Cochrane Risk of Bias tool. The primary outcome was overall breast cancer incidence, with secondary outcomes including invasive breast cancer and ductal carcinoma in situ. NMA was performed using a random-effects model, measuring efficacy with risk ratios (RR) and number needed to treat (NNT). Medications were ranked using the Surface Under the Cumulative RAnking curve (SUCRA). We performed subgroup analyses by menopause status, primary versus secondary/other outcomes, follow-up, and intervention duration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Out of 8,598 studies screened, 43 RCTs (n = 337,240 women) met inclusion criteria. Six medications reduced overall breast cancer risk compared to placebo: sulfonylurea (RR = 0.18, 95% CI = 0.04-0.91, NNT = 44.1, SUCRA = 0.90), thiazolidinediones (RR = 0.25, 95% CI = 0.08-0.78, NNT = 48.3, SUCRA = 0.80), third-generation selective estrogen receptor modulators (SERMs) (RR = 0.46, 95% CI = 0.33-0.66, NNT = 67.3, SUCRA = 0.62), aromatase inhibitors (AIs) (RR = 0.50, 95% CI = 0.39-0.66, NNT = 73.0, SUCRA = 0.55), raloxifene (RR = 0.63, 95% CI = 0.47-0.84, NNT = 96.9, SUCRA = 0.37), and tamoxifen (RR = 0.76, 95% CI = 0.65-0.88, NNT = 149.7, SUCRA = 0.23). AIs (RR = 0.48, 95% CI = 0.33-0.71), tamoxifen (RR = 0.63, 95% CI = 0.51-0.78), and raloxifene (RR = 0.63, 95% CI = 0.47-0.86), were effective for invasive breast cancer. Third-generation SERMs (RR = 0.46, 95% CI = 0.32-0.67), AIs (RR = 0.51, 95% CI = 0.40-0.64), raloxifene (RR = 0.61, 95% CI = 0.46-0.82), and tamoxifen (RR = 0.76, 95% CI = 0.66-0.86) were effective in studies with breast cancer as a primary outcome, while thiazolidinediones (RR = 0.25, 95% CI = 0.07-0.84) were effective in studies with breast cancer as a secondary/other outcome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This NMA confirms the efficacy of tamoxifen, raloxifene, and AIs, and identifies thiazolidinediones and third-generation SERMs as promising agents for breast cancer prevention, though not currently included in guidelines. These findings extend prior evidence and highlight the need for trials in premenopausa","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"118"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545766","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":"Cancer-associated fibroblast driven paracrine IL-6/STAT3 signaling promotes migration and dissemination in invasive lobular carcinoma.","authors":"Esme Bullock, Aleksandra Rozyczko, Sana Shabbir, Ifigenia Tsoupi, Adelaide I J Young, Jana Travnickova, Laura Gómez-Cuadrado, Zeanap Mabruk, Giovana Carrasco, Elizabeth Morrow, Kathryn Pennel, Pim Kloosterman, Julia M Houthuijzen, Jos Jonkers, Lidia Avalle, Valeria Poli, Richard Iggo, Xue Xiao, Jingjing Guo, Xuan Zhu, Elizabeth Mallon, Joanne Edwards, E Elizabeth Patton, Valerie G Brunton","doi":"10.1186/s13058-025-02074-x","DOIUrl":"10.1186/s13058-025-02074-x","url":null,"abstract":"<p><strong>Background: </strong>Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma of no special type (NST), accounting for 10-15% of diagnoses. Despite the myriad molecular, histological and clinical differences between ILC and NST tumors, patients are treated in the same way, and although prognosis initially is good, ILC patients have poorer long-term outcomes. Understanding the differences between these two subtypes and identifying ILC-enriched therapeutic targets is necessary to improve patient care.</p><p><strong>Methods: </strong>Human and mouse cancer-associated fibroblasts (CAFs), ILC cell lines and patient-derived organoids were used for in vitro and in vivo studies, including western blotting, migration, organotypic invasion assays and dissemination in zebrafish embryos. RNASeq was used to identify CAF and interleukin-6 (IL-6)-derived gene signatures. Bioinformatic analysis of public databases and immunohistochemical of human tumor microarrays was carried out.</p><p><strong>Results: </strong>We identified IL-6 as a paracrine CAF-derived factor that activates Signal-Transducer-and-Activator-of-Transcription-3 (STAT3) in human and mouse ILC models. Analysis of human breast tumors showed that the IL-6/JAK/STAT3 pathway is enriched in ER + ILC compared to ER + NST. A 42-gene CAF dependent IL-6 gene signature and 64-gene consensus IL-6 gene signature were generated and were significantly enriched in ER + ILC, with many of the genes overexpressed in ILC tumors. IL-6 treatment suppressed downstream estrogen signaling and also led to the acquisition of a more mesenchymal-like phenotype associated with increased migration and invasion. Finally, IL-6 treatment significantly increased ILC cell dissemination following injection into zebrafish embryos.</p><p><strong>Conclusions: </strong>CAF-derived IL-6 drives paracrine activation of the IL6/JAK/STAT3 signaling pathway which is enriched in ILC. This leads to the acquisition of pro-tumorigenic phenotypes, highlighting the pathway as a potential therapeutic target in ILC.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"121"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545792","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":"Retrospective comparison between breast cancer tissue- and blood-based next-generation sequencing results in detection of PIK3CA, AKT1, and PTEN alterations.","authors":"Moumita Chaki, Mona Benrashid, Subir Puri, Smruthy Sivakumar, Ethan S Sokol, Josefa M Briceno, Neil Vasan","doi":"10.1186/s13058-025-02055-0","DOIUrl":"10.1186/s13058-025-02055-0","url":null,"abstract":"<p><strong>Background: </strong>Based on the CAPItello-291 phase III trial results, capivasertib in combination with fulvestrant has been approved for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer harboring one or more PIK3CA, AKT1, and/or PTEN alterations. Given the growing interest in circulating tumor DNA (ctDNA) next-generation sequencing (NGS) to detect PIK3CA/AKT1/PTEN alterations, we retrospectively compared blood-based FoundationOne®Liquid CDx versus tumor tissue-based FoundationOne®CDx real-world data from patients with various breast cancer subtypes.</p><p><strong>Methods: </strong>We utilized a database of patients profiled with FoundationOne®CDx and/or FoundationOne®Liquid CDx during routine clinical care. Analytical comparison of all pathogenic alterations in PIK3CA, AKT1, AKT2, AKT3, and PTEN, including alterations defined in the CAPItello-291 protocol (CAPItello-defined alterations), was performed in paired data from 289 patients with both tissue and liquid biopsies sampled within 90 days of each other.</p><p><strong>Results: </strong>Overall positive percent agreement (PPA) for short variants across ctDNA tumor fraction (TF) subgroups in paired biopsy samples was: ctDNA TF ≥ 10%: PIK3CA, 93.9%; AKT1, 100%; PTEN, 100%; ctDNA TF 1%-10%: PIK3CA, 96.3%; AKT1, 100%; PTEN, 100%; ctDNA TF < 1%: PIK3CA, 34.7%; AKT1, 50.0%; PTEN, 37.5%. PPA for CAPItello-defined alterations was: ctDNA TF ≥ 10%: 92.5%; ctDNA TF 1%-10%: 97.1%; ctDNA TF < 1%: 33.9%. For PTEN homozygous deletions, PPA was 50.0% in cases with ctDNA TF ≥ 10%. Overall PPA for AKT2 and AKT3 copy number variations (CNVs) was 66.7% and 0%, respectively.</p><p><strong>Conclusions: </strong>Blood-based NGS could offer a minimally invasive option to identify clinically relevant PIK3CA/AKT1/PTEN short variants in cases with ctDNA TF ≥ 1%. Confirmatory tissue-based NGS should be performed when blood-based NGS results are negative, especially when ctDNA TF is < 1% and for enhanced detection of CNVs in general.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"122"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545769","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":"Correction: Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.","authors":"Ricardo Ribas, Sunil Pancholi, Aradhana Rani, Eugene Schuster, Stephanie K Guest, Joanna Nikitorowicz-Buniak, Nikiana Simigdala, Allan Thornhill, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Mitch Dowsett, Stephen R Johnston, Lesley-Ann Martin","doi":"10.1186/s13058-025-02046-1","DOIUrl":"10.1186/s13058-025-02046-1","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"116"},"PeriodicalIF":7.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486778","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":"Systemic glucocorticoids and the risk of breast cancer in a large nationwide case-control study.","authors":"Manon Cairat, Morten Olesen, Elea Olivier, Anton Pottegård, Blánaid Hicks","doi":"10.1186/s13058-025-02071-0","DOIUrl":"10.1186/s13058-025-02071-0","url":null,"abstract":"<p><strong>Background: </strong>Concerns have been raised that long-term use of glucocorticoids may increase the risk of breast cancer, yet evidence is limited. Thus, this study investigated the association between systemic glucocorticoid use and breast cancer risk, overall and by breast cancer subtype and stage.</p><p><strong>Methods: </strong>A nationwide case-control study was conducted using the Danish healthcare registries. Women with invasive breast cancer between 2001 and 2018 (n = 67,829) were identified as cases. Each case was matched to 10 population controls on age and calendar time. Ever users of glucocorticoids were defined as women who filled at least 2 prescriptions and long-term users those who filled prescriptions equivalent to ≥ 1000 defined daily doses (DDDs). Conditional logistic regressions were performed to calculate odds ratios (ORs) and 95% confidence intervals for the associations between glucocorticoid use and breast cancer risk.</p><p><strong>Results: </strong>Twelve percent of women (n = 87,277) had ever been exposed to glucocorticoids and fewer than 1% were long-term users (n = 5,574). No association was found between ever use of glucocorticoids and breast cancer risk [OR = 1.00 (0.98-1.03)], compared with never use. However, an inverse association was observed between long-term glucocorticoid use and breast cancer risk [OR = 0.87 (0.77-0.97)], with suggestion of a slight dose-response relationship [OR per 500 DDDs = 0.96 (0.94-0.99)]. The associations were consistent across different tumour subtypes, estrogen receptor status, or clinical stage at diagnosis.</p><p><strong>Conclusion: </strong>The findings from this large nationwide study did not suggest a positive association between glucocorticoids and breast cancer risk.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"114"},"PeriodicalIF":7.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477499","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":"Anti-cancer drug sensitivity testing and preclinical evaluation of the anti-cancer potential of WEE1 inhibitor in triple-negative breast cancer patient-derived organoids and xenograft models.","authors":"Seungyeon Ryu, Hoe Suk Kim, Sangeun Lee, So-Hyun Yoon, Moonjou Baek, A Young Park, Han-Byoel Lee, Ga Yeon Kim, Kyung Hyeun Park, Ji-Jung Jung, Yireh Han, Dong Woo Lee, Bosung Ku, Wonshik Han","doi":"10.1186/s13058-025-02063-0","DOIUrl":"10.1186/s13058-025-02063-0","url":null,"abstract":"<p><strong>Background: </strong>Relevant surrogates that maintain the pathological and physiological properties of patient tumors are essential for guiding triple-negative breast cancer (TNBC) therapy. The goals are to generate patient-derived organoids (PDOs), xenografts (PDXs), and PDX-derived organoids (PDXOs), evaluate the therapeutic potential of the WEE1 inhibitor AZD1775, and compare their responses to 18 anti-cancer drugs in PDOs and PDXOs.</p><p><strong>Methods: </strong>PDOs were produced from surgical specimens of patients with TNBC. PDXs were generated by transplanting PDOs into the mammary fat pads of NOD.Cg-Prkdcscid Il2rgtm1wjl/SzJ mice. PDXOs were derived from fresh tumor specimens of PDXs. For drug efficacy, half-maximal inhibitory concentration (IC50) values for 18 anti-cancer drugs on PDOs and PDXOs were calculated using the CellTiter-Glo® 3D cell viability assay in a high-throughput drug screening system. The relationship between WEE1 expression and survival in TNBC-basal-like (BL) patients was analyzed using the Kaplan-Meier Plotter database. Mice were treated with AZD1775 via oral gavage (30 mg/kg). Biological mechanisms underlying the anti-cancer drug responses were evaluated by calcein-AM staining, caspase 3/7 staining, Western blot, flow cytometry, and immunohistochemistry.</p><p><strong>Results: </strong>PDOs were established through subcultures of 2-7 passages. TNBC-BL PDXs expressing CK5, vimentin, and EGFR were generated and expanded over 3-4 generations of transplantation. PDXOs were produced through subcultures of 4-5 passages. PDOs, PDXs, and PDXOs retained the immunohistological characteristics of the relevant patients with TNBC. WEE1 was associated with poor survival outcomes in TNBC-BL patients. The highest cytotoxicity and tumor growth suppression to AZD1775 therapy were observed in PDXOs and PDXs with high WEE1 expression. AZD1775 inhibited WEE1 and CDK1 phosphorylation, increased γH2AX phosphorylation, induced G2/M arrest, and activated caspase 3/7 in PDXOs and PDXs, all associated with DNA damage, mitotic catastrophe, and apoptosis. Anti-cancer drug responses were highly concordant between matched PDOs and PDXOs. The responses of PDOs and PDXOs to anti-cancer drugs were comparable to those of patients receiving neoadjuvant or adjuvant chemotherapy, according to clinical records.</p><p><strong>Conclusion: </strong>PDOs, PDXOs, and PDXs, which maintained the immunological properties of TNBC patient, provide a scientific rationale for future WEE1-targeted clinical trials in TNBC. PDOs and PDXOs represent cost- and time-effective surrogates for predicting prioritized personalized therapy.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"113"},"PeriodicalIF":7.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477496","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":"Combined prognostic impact of initial clinical stage and residual cancer burden after neoadjuvant systemic therapy in triple-negative and HER2-positive breast cancer: an analysis of the I-SPY2 randomized clinical trial.","authors":"Roberto A Leon-Ferre, K Dimitroff, C Yau, K V Giridhar, R Mukhtar, G Hirst, N Hylton, J Perlmutter, A DeMichele, D Yee, L van 't Veer, H Rugo, W F Symmans, M P Goetz, L Esserman, J C Boughey","doi":"10.1186/s13058-025-02070-1","DOIUrl":"10.1186/s13058-025-02070-1","url":null,"abstract":"<p><strong>Background: </strong>Operable triple-negative (TNBC) and HER2-positive breast cancer are often treated with neoadjuvant systemic therapy (NAST). NAST response is highly prognostic, with pathologic complete response (pCR) being associated with low risk of recurrence or death. In contrast, residual disease (RD) after NAST is associated with higher risks and is an indication for escalated postoperative therapy. Recent studies suggest that tumor (T) size and nodal (N) status at diagnosis influence clinical outcomes independent of NAST response. We evaluated the impact of initial clinical stage on clinical outcomes according to response to NAST in I-SPY2.</p><p><strong>Patients and methods: </strong>Patients with stage II or III TNBC or HER2-positive breast cancer treated on the I-SPY2 trial (NCT01042379) with required data on clinical T size and N status prior to NAST, residual cancer burden (RCB) index, recurrence and survival were included. Survival outcomes, including event-free (EFS), distant recurrence-free (DRFS), and overall survival (OS), were assessed using multivariable Cox proportional hazard models.</p><p><strong>Results: </strong>Among 1,033 patients (TNBC: 638, HER2-positive: 395), the median follow-up was 4.4 years (range 0.3-10.2). 47% achieved pCR (TNBC: 44%, HER2-positive: 51%). Smaller baseline T size, but not N status, was associated with higher pCR rates. However, in those not achieving pCR, RCB class was correlated with both baseline T size and N status in TNBC, and with baseline N status (but not T size) in HER2-positive. Among patients with RD, larger baseline T size was independently associated with worse EFS and DRFS in TNBC and HER2-positive, and with OS in TNBC; while N status was associated with EFS and DRFS in TNBC on univariate analysis only. We did not identify an association between baseline T size or N status and outcomes in patients achieving pCR.</p><p><strong>Conclusions: </strong>Tumor size at diagnosis remained an independent prognostic factor in patients with TNBC and HER2-positive breast cancer with RD after NAST. In contrast, patients achieving pCR had excellent outcomes regardless of initial disease extent, supporting the relevance of pCR as a surrogate endpoint in breast cancer.</p><p><strong>Trial registration: </strong>I-SPY 2 TRIAL beginning December 31, 2009: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY 2), NCT01042379.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"115"},"PeriodicalIF":7.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477497","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":"In vivo imaging of the spatial heterogeneity of intratumoral acidosis (pH) as a marker of the metastatic phenotype in breast cancer.","authors":"Alessia Corrado, Nicla Lorito, Annasofia Anemone, Antonella Carella, Daisy Villano, Elisa Pirotta, Francesco Gammaraccio, Angela Subbiani, Marina Bacci, Walter Dastrù, Andrea Morandi, Dario Livio Longo","doi":"10.1186/s13058-025-02065-y","DOIUrl":"10.1186/s13058-025-02065-y","url":null,"abstract":"<p><strong>Background: </strong>Metabolic alterations, including acidosis in the tumor microenvironment, have been extensively linked to more aggressive phenotypes and increased therapy resistance. However, current imaging techniques are limited in their ability to capture extracellular tumor acidosis precisely and assess spatial heterogeneity in vivo, making its association with augmented malignancy poorly understood. In this study, we investigated whether Magnetic Resonance Imaging- Chemical Exchange Saturation Transfer (MRI-CEST) technique for tumor pH imaging of intratumoral acidosis could differentiate between metastatic and non-metastatic breast cancers.</p><p><strong>Methods: </strong>Isogenic metastatic (4T1) and non-metastatic (67NR) breast cancer cell lines were characterized for their metabolic and acidosis features, including LDH-A/PDK-1 expression, glucose consumption, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Potential relationship between tumor acidosis, vascularization and hypoxia with metastatic potential was assessed in vivo by MRI-based imaging approaches in orthotopic breast tumors. Validation of MRI findings was assessed ex vivo by western blot, immunohistochemistry and immunofluorescence assays for a multiparametric characterization of tumor microenvironment and metabolic properties.</p><p><strong>Results: </strong>We observed a higher energetic profile of the 4T1 cells compared to the 67NR cells, alongside elevated glycolytic (LDH-A, PDK-1), hypoxia (CAIX, Pimonidazole), and vascularization (CD31) markers in 4T1 orthotopic primary tumors, which were associated with a greater metastatic propensity. MRI-CEST tumor pH imaging revealed increased extracellular tumor acidity in 4T1 tumors, along with marked spatial intratumoral heterogeneity, in contrast to the more homogenous 67NR tumors, as further confirmed by LAMP-2 staining. Notably, this spatial intratumor heterogeneity in acidosis enables clear differentiation between high- and low-malignancy tumors.</p><p><strong>Conclusions: </strong>These findings underscore the role of tumor acidosis and its spatial heterogeneity in promoting aggressive phenotypes and highlight the potential of in vivo tumor pH imaging as a marker of malignancy in breast cancers.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"112"},"PeriodicalIF":7.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477498","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}