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Zubareva EY, Senchukova MA, Saidler NV. Cytoplasmic and nuclear programmed death ligand 1 expression in peritumoral stromal cells in breast cancer: Prognostic and predictive value. World J Exp Med 2025; 15:102761. [DOI: 10.5493/wjem.v15.i2.102761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 01/21/2025] [Accepted: 02/21/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Breast cancer (BC) continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population. One of the promising markers associated with BC progression is programmed death ligand 1 (PD-L1). Previously, we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1 (PDCD1 LG1) and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC. However, the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.
AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.
METHODS In a prospective single-center observational study, tumor samples from 148 patients with newly diagnosed BC were examined. The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1. In the tumor samples, the PDCD1 LG1-positive lymphocyte (PDCD1 LG1+ LF) score, presence of nuclear PDCD1 LG1 expression in the LFs, PDCD1 LG1 expression in polymorphic cell infiltrates (PDCD1 LG1+ polymorphic cell infiltrates [PCIs]), and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed. Statistical analyses were performed using Statistica 10.0 software.
RESULTS A PDCD1 LG1+ LF score ≥ 3 was detected more often at stages N0 and N3 than at N1 and N2 (P = 0.03). Moderate and pronounced PDCD1 LG1+ PCIs and the presence of PDCD1 LG1+ fibroblastic stroma were associated with negative estrogen receptor status (P = 0.0008 and P = 0.03, respectively), human epidermal growth factor receptor 2-positive (HER2+) BC (P < 0.00001 and P = 0.0005), and luminal B HER2+, non-luminal HER2+ and triple-negative BC (P < 0.00001 and P = 0.004). The risk of metastasis to regional lymph nodes (RLNs) depend on lymphovascular invasion (LVI) and the PDCD1 LG1+ LF score. In the absence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were absent in 66.6% and 93.9% of patients with BC, respectively. In the presence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were detected in 82.6% and 92.7% of patients with BC, respectively.
CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+ LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.
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Affiliation(s)
- Evgeniya Yu Zubareva
- Department of Oncology, Orenburg State Medical University, Orenburg 460021, Orenburgskaya Oblast, Russia
| | - Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460021, Orenburgskaya Oblast, Russia
| | - Natalia V Saidler
- Department of Pathology, Orenburg Regional Cancer Clinic, Orenburg 460021, Orenburgskaya Oblast, Russia
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Biganzoli G, Isnaldi E, Richard F, Marano G, Boracchi P, Maetens M, Floris G, Neven P, Jerusalem G, Munzone E, Hitre E, Gombos A, Thompson A, Aebi S, Kammler R, Dell'Orto P, Viale G, Regan MM, Colleoni M, Biganzoli E, Desmedt C. Prognostic relation of body mass index on extended aromatase inhibition treatment in postmenopausal patients with estrogen receptor positive breast cancer: A retrospective analysis of the SOLE trial. Eur J Cancer 2025; 222:115438. [PMID: 40286474 PMCID: PMC12118534 DOI: 10.1016/j.ejca.2025.115438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 03/31/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Obesity is associated with a greater risk of developing distant recurrences in patients with estrogen receptor-positive (ER+) breast cancer. This association is however poorly investigated in patients treated with extended endocrine treatment (ET). We therefore evaluated the prognostic role of BMI in the SOLE trial, where postmenopausal patients, after having completed 4-6 years of adjuvant ET, were treated with 5 additional years of continuous or intermittent letrozole. PATIENTS & METHODS We considered the 3606 patients with ER+ /HER2- lymph node-positive BC with available BMI from the SOLE trial (NCT00553410). Distant-recurrence free interval (DRFI) was the main endpoint, and breast cancer-free interval (BCFI), disease-free survival (DFS) and overall survival (OS) secondary endpoints. Adjusted risk ratios (RR) for distant metastases were estimated with crude cumulative incidence models. RESULTS 38.6 % of the patients were underweight or normal weight, 36.5 % overweight and 24.9 % obese. BMI was associated with age, tumor size, number of positive lymph nodes, menopausal status and type of prior ET. In the adjusted analyses, the prognostic value of BMI was dependent on prior ET and extended ET arm (second-order interaction p-value<0.001 for DRFI, BCFI and DFS, but not for OS). For instance, in patients treated with both a selective estrogen receptor modulator and an aromatase inhibitor in the first five years, obesity, as compared to normal-weight, was associated with better (RRDRFI=0.61, 95 %CI: 0.42-0.90) and worse (RRDRFI=2.31, 95 %CI: 1.41-3.78) outcomes in the adjusted models, in patients treated with continuous and intermittent letrozole in the extended ET, respectively. CONCLUSION We observed that the prognostic relation of BMI changes according to the type of adjuvant ET and mode of administration of extended AI. This warrants further investigation.
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Affiliation(s)
- Giacomo Biganzoli
- Unit of Medical Statistics, Biometry and Epidemiology, Department of Biomedical and Clinical Sciences (DIBIC) "L. Sacco" & DSRC, LITA Vialba campus, University of Milan, Milan, Italy
| | - Edoardo Isnaldi
- KU Leuven, Department of Oncology, Laboratory for Translational Breast Cancer Research, Leuven, Belgium
| | - François Richard
- KU Leuven, Department of Oncology, Laboratory for Translational Breast Cancer Research, Leuven, Belgium
| | - Giuseppe Marano
- Unit of Medical Statistics, Biometry and Epidemiology, Department of Biomedical and Clinical Sciences (DIBIC) "L. Sacco" & DSRC, LITA Vialba campus, University of Milan, Milan, Italy
| | - Patrizia Boracchi
- Unit of Medical Statistics, Biometry and Epidemiology, Department of Biomedical and Clinical Sciences (DIBIC) "L. Sacco" & DSRC, LITA Vialba campus, University of Milan, Milan, Italy
| | - Marion Maetens
- KU Leuven, Department of Oncology, Laboratory for Translational Breast Cancer Research, Leuven, Belgium
| | - Giuseppe Floris
- KU Leuven, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, Leuven, Belgium; University Hospitals Leuven, Department of Pathology, Leuven, Belgium
| | - Patrick Neven
- Gynecologic Oncology and Multidisciplinary Breast Center, University Hospitals UZ-Leuven, KU Leuven, Leuven, Belgium
| | - Guy Jerusalem
- Medical Oncology Department, CHU Liège, Liège University, Liège, Belgium
| | - Elisabetta Munzone
- Division of Medical Senology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Erika Hitre
- Department of Medical Oncology and Clinical Pharmacology "B", National Institute of Oncology, Budapest, Hungary
| | - Andrea Gombos
- Medical Oncology Department, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Alastair Thompson
- Division of Surgical Oncology, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, USA
| | - Stefan Aebi
- Division of Medical Oncology, Cancer Center, Lucerne Cantonal, Hospital, Lucerne, Switzerland; Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Roswitha Kammler
- Translational Research Coordination, ETOP IBCSG Partners Foundation, Bern, Switzerland
| | | | - Giuseppe Viale
- IBCSG Central Pathology Office, Milan, Italy; Department of Pathology and Laboratory Medicine, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Meredith M Regan
- IBCSG Statistical Center, Division of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - Marco Colleoni
- Division of Medical Senology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Elia Biganzoli
- Unit of Medical Statistics, Biometry and Epidemiology, Department of Biomedical and Clinical Sciences (DIBIC) "L. Sacco" & DSRC, LITA Vialba campus, University of Milan, Milan, Italy; KU Leuven, Department of Oncology, Laboratory for Translational Breast Cancer Research, Leuven, Belgium
| | - Christine Desmedt
- KU Leuven, Department of Oncology, Laboratory for Translational Breast Cancer Research, Leuven, Belgium.
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Giudici F, Toffolutti F, Guzzinati S, Schettini F, Bortul M, Francisci S, Zorzi M, De Vidi S, Pierannunzio D, Dal Maso L. A population-based estimation of breast cancer recurrence in northeast Italy with administrative healthcare databases. Breast 2025; 82:104487. [PMID: 40339310 DOI: 10.1016/j.breast.2025.104487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/15/2025] [Accepted: 04/30/2025] [Indexed: 05/10/2025] Open
Abstract
BACKGROUND/AIM Information on the long-term frequency of recurrence is of paramount importance for the increasing number of women living several years after breast cancer (BC) diagnosis and for their caregivers. The study aims to estimate the cumulative incidence of recurrence until 10 years after diagnosis in Italian women diagnosed with BC using population-based cancer registries. METHODS Women diagnosed with stage I to III BC during 2004-2010 from Friuli Venezia Giulia and Veneto (Italy) cancer registries were included (n = 5825). Recurrence status after a disease-free period was ascertained through individual-level linked databases using treatment or procedure codes from claims. Cumulative incidence of recurrence was calculated in the presence of competing risks (second cancer or death). RESULTS During a median follow-up of 13.5 years, 1522 out of 5825 women experienced a recurrence with an estimated 10-years cumulative incidence of 20.8 % (95 %CI:19.7-21.8 %), decreasing from 23.7 % in 2004-2006 to 18.5 % in 2007-2010. Women younger than 40 years (40.5 %), with stage III (41.8 %) and triple-negative BC (32.5 %) showed a higher 10-year incidence of recurrence. At 10 years after a BC diagnosis, 83.9 % of women were alive: 67.5 % without any cancer-related events, 12.4 % after recurrence and 4.0 % after second primary cancer. 10-years survival was higher than 90 % for women with stage I BC and 58.1 % for those with stage III (3.2 % and 27.3 % deaths after recurrence, respectively). DISCUSSION This Italian study provide detailed population-based information on the incidence of recurrence and other outcomes after BC and may be replicated in other Italian and European areas.
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Affiliation(s)
- Fabiola Giudici
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
| | - Federica Toffolutti
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | | | - Francesco Schettini
- Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Marina Bortul
- Division of General Surgery, Department of Medical and Surgical Sciences, Breast Unit, Cattinara University Hospital, Trieste, Italy
| | - Silvia Francisci
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Manuel Zorzi
- Epidemiological Department, Azienda Zero, Padua, Italy
| | - Sara De Vidi
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Daniela Pierannunzio
- National Centre for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy
| | - Luigino Dal Maso
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
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Tauber N, Amann N, Dannehl D, Deutsch TM, Dimpfl M, Fasching P, Hartkopf A, Heublein S, Hilmer L, Hörner M, Krawczyk N, Krückel A, Krug D, Marmé F, Michel LL, Reinisch M, Rody A, Schäffler H, Schneeweiss A, Utz D, Veselinovic K, Banys-Paluchowski M. Therapy of early breast cancer: current status and perspectives. Arch Gynecol Obstet 2025:10.1007/s00404-025-08028-0. [PMID: 40261372 DOI: 10.1007/s00404-025-08028-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 04/01/2025] [Indexed: 04/24/2025]
Abstract
Medical advancements in breast cancer are truly remarkable. Especially in recent years, numerous new therapeutics have been approved and surgical strategies have been de-escalated for specific patient groups. In the therapeutic setting, CDK4/6 inhibitors as oral maintenance therapy in early breast cancer and immune checkpoint inhibitors (Pembrolizumab) for triple-negative breast cancer (BC) are noteworthy. In the surgical field, prospective randomized controlled trials have currently explored the possibility to deescalate axillary surgery by omitting sentinel lymph node excision (INSEMA, SOUND). As a result, there have been significant improvements in prognosis and a reduction in surgical morbidity for patients. Many exciting trials are underway, and it remains to be seen whether antibody-drug conjugates beyond trastuzumab emtansine, will find their way into the treatment lines for early-stage BC. Furthermore, the integration of artificial intelligence in both diagnostics and treatment recommendation evaluation is a promising area with great potential.
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Affiliation(s)
- Nikolas Tauber
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
| | - Niklas Amann
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - Dominik Dannehl
- Department of Obstetrics and Gynecology, University Hospital Tuebingen, 72016, Tuebingen, Germany
| | - Thomas M Deutsch
- Department of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany
| | - Moritz Dimpfl
- Department of Obstetrics and Gynecology, Medical Faculty Mannheim, University Medical Center Mannheim, University of Heidelberg, Mannheim, Deutschland
| | - Peter Fasching
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - Andreas Hartkopf
- Department of Obstetrics and Gynecology, University Hospital Tuebingen, 72016, Tuebingen, Germany
| | - Sabine Heublein
- Department of Obstetrics and Gynecology, University Hospital Ulm, 89075, Ulm, Germany
| | - Lisbeth Hilmer
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Manuel Hörner
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - Natalia Krawczyk
- Department of Obstetrics and Gynecology, University Hospital Duesseldorf, 40225, Duesseldorf, Germany
| | - Annika Krückel
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - David Krug
- Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frederik Marmé
- Department of Obstetrics and Gynecology, Medical Faculty Mannheim, University Medical Center Mannheim, University of Heidelberg, Mannheim, Deutschland
| | - Laura L Michel
- National Center for Tumor Diseases, University Hospital and German Cancer Research Center Heidelberg, 69120, Heidelberg, Germany
| | - Mattea Reinisch
- Department of Obstetrics and Gynecology, Medical Faculty Mannheim, University Medical Center Mannheim, University of Heidelberg, Mannheim, Deutschland
| | - Achim Rody
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Henning Schäffler
- Department of Obstetrics and Gynecology, University Hospital Ulm, 89075, Ulm, Germany
| | - Andreas Schneeweiss
- National Center for Tumor Diseases, University Hospital and German Cancer Research Center Heidelberg, 69120, Heidelberg, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
| | - David Utz
- Department of Internal Medicine VIII, Medical Oncology and Pneumology, University Hospital Tuebingen, 72016, Tuebingen, Germany
| | - Kristina Veselinovic
- Department of Obstetrics and Gynecology, University Hospital Ulm, 89075, Ulm, Germany
| | - Maggie Banys-Paluchowski
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
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Santucci C, Mignozzi S, Levi F, Malvezzi M, Boffetta P, Negri E, La Vecchia C. European cancer mortality predictions for the year 2025 with focus on breast cancer. Ann Oncol 2025; 36:460-468. [PMID: 40074664 DOI: 10.1016/j.annonc.2025.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/10/2025] [Accepted: 01/21/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND We predicted the number of cancer deaths and rates for 2025 in the European Union (EU), its five most populous countries, and the UK, focusing on breast cancer. MATERIALS AND METHODS We derived population data and death certificates for all cancers and major sites for the EU, France, Germany, Italy, Poland, Spain, and the UK since 1970, from the World Health Organization and United Nations databases. Estimates for 2025 were computed by linear regression on recent trends identified through Poisson joinpoint regression, considering the slope of the most recent trend segment. Deaths averted from 1989 to 2025 were calculated by applying the 1988 peak rate to subsequent population data. RESULTS We estimated 1 280 000 cancer deaths in the EU in 2025, corresponding to age-standardised rates (ASRs) of 120.9/100 000 males (-3.5% versus 2020) and 79.1/100 000 females (-1.2%). In the UK, we predicted 173 000 cancer deaths and ASRs of 101.2/100 000 males (-10.1%) and 82.1/100 000 females (-6.3%). In the EU, favourable trends are predicted for major neoplasms, except pancreatic cancer, in males (+2.0%) and females (+3.0%), and lung (+3.8%) and bladder (+1.9%) cancers among females. Breast cancer mortality showed favourable trends in all countries. Substantial decreases were predicted for EU females aged 50-69 years (-9.8%) and 70-79 years (-12.4%). Between 1989 and 2025, we estimated about 6.8 million averted cancer deaths in the EU, including over 373 000 breast cancer deaths. Corresponding numbers for the UK were 1 500 000 and 197 000. CONCLUSION EU breast cancer rates have fallen by 30% since 1990, due to advances in prevention, treatment, and early detection. Contrasting trends in lung cancer among males and females reflect differing tobacco smoking patterns. Female lung cancer mortality is still increasing in the EU, though less than in the previous decade. Persistent unfavourable pancreatic cancer trends can be related to the increasing prevalence of obesity and limited therapeutic advances, requiring continued attention.
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Affiliation(s)
- C Santucci
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - S Mignozzi
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - F Levi
- Department of Epidemiology and Health Services Research, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - M Malvezzi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - P Boffetta
- Stony Brook Cancer Center, Stony Brook University, Stony Brook, USA; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - E Negri
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - C La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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Jie H, Ma W, Huang C. Diagnosis, Prognosis, and Treatment of Triple-Negative Breast Cancer: A Review. BREAST CANCER (DOVE MEDICAL PRESS) 2025; 17:265-274. [PMID: 40124876 PMCID: PMC11928298 DOI: 10.2147/bctt.s516542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/08/2025] [Indexed: 03/25/2025]
Abstract
Triple-negative breast cancer (TNBC) has become the most aggressive and worst prognostic subtype of breast cancer due to the lack of estrogen receptor, progesterone receptor and HER2 expression. This article systematically reviews the progress in the diagnosis, prognosis and treatment of TNBC. In terms of diagnosis, imaging techniques (such as dynamic contrast-enhanced MRI and multimodality ultrasound) combined with histological and immunohistochemical detection (such as Ki-67, PD-L1 expression) can improve the early diagnosis rate; molecular markers (PIM-1, miR-522) and subtype classification (LAR, IM, BLIS, MES) provide the basis for accurate classification. Prognostic evaluation requires a combination of clinicopathologic features (tumor size, lymph node metastasis, tumor-to-stroma ratio), molecular characteristics (BRCA mutation, PD-L1 expression), and prognostic scoring systems. In treatment strategies, chemotherapy remains the basis, but efficacy and side effects need to be balanced; neoadjuvant chemotherapy can improve the pathological complete response rate, while molecular markers (such as circulating tumor cells) help predict efficacy. In terms of targeted therapy, PARP inhibitors are significantly effective in patients with BRCA mutations, and antibody drug conjugates (eg, sacituzumab govitecan) provide new options for chemoresistant patients. In immunotherapy, PD-1/PD-L1 inhibitors combined with chemotherapy significantly improved progression-free survival, especially for PD-L1-positive patients. Combined therapy, metabolic reprogramming, and individualized treatment strategies need to be further explored in the future to overcome the heterogeneity and treatment resistance of TNBC. This article emphasizes the key role of multidisciplinary collaboration and precision medicine in optimizing TNBC management and provides an important reference for clinical practice and research direction.
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Affiliation(s)
- Huan Jie
- Department of Oncology, No. 926 hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China
| | - Wenhui Ma
- Department of Radiology, No. 926 hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China
| | - Cong Huang
- Department of Radiology, No. 926 hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China
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Li Y, Luo H, Lin X, Hua L, Wang J, Xie J, Zhang Z, Shi Z, Li M, Peng Q, Lin L, Liao D, Xia B. Triterpenes of Prunella vulgaris Inhibit Triple-Negative Breast Cancer by Regulating PTP1B/PI3K/AKT/mTOR and IL-24/CXCL12/CXCR4 Pathways. Int J Mol Sci 2025; 26:1959. [PMID: 40076586 PMCID: PMC11900149 DOI: 10.3390/ijms26051959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 02/14/2025] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by high molecular heterogeneity. Owing to the lack of effective therapeutic strategies, patients with TNBC have a poor prognosis. Prunella vulgaris L. has the effects of reducing swelling, dissolving knots and treating breast carbuncles and mammary rocks. Modern pharmacological studies have reported that it can effectively inhibit the growth of breast cancer. The main active antitumor components of Prunella vulgaris are triterpenoids (PVT); however, the role and potential mechanism of PVT in TNBC remain unexplored. Our study aimed to further explore the inhibitory effects of PVT on TNBC and the associated mechanism. The results showed that 19 compounds associated with PVT were identified, 9 of which were triterpenoids. The percentages of ursolic acid and oleanolic acid in PVT were 34.51% and 11.32%, respectively. Triterpenes of Prunella vulgaris significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells and promoted their apoptosis in a concentration-dependent manner. PVT could also effectively downregulate the mRNA and protein expression levels of Ptp1b, Pi3k, Akt and mtor and upregulate the mRNA and protein expression levels of Il-24 in MDA-MB-231 cells. In mice with tumors of TNBC, PVT significantly reduced tumor growth and the expression levels of PTP1B, CXCL12, CXCR4, PI3K, AKT, mTOR and other proteins in TNBC tumor tissue and upregulated the expression of IL-24. This study showed that PVT played an anti-TNBC role by regulating the PTP1B/PI3K/AKT/mTOR signaling pathway and the IL-24/CXCL12/CXCR4 signaling axis.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Duanfang Liao
- Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (Y.L.); (H.L.); (X.L.); (L.H.); (J.W.); (J.X.); (Z.Z.); (Z.S.); (M.L.); (Q.P.); (L.L.)
| | - Bohou Xia
- Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (Y.L.); (H.L.); (X.L.); (L.H.); (J.W.); (J.X.); (Z.Z.); (Z.S.); (M.L.); (Q.P.); (L.L.)
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8
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Carausu M, Neven P, Ignatiadis M. Expanding the role of CDK4/6 inhibitors in early breast cancer: insights from the NATALEE trial. Ann Oncol 2025; 36:127-129. [PMID: 39880556 DOI: 10.1016/j.annonc.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 01/07/2025] [Indexed: 01/31/2025] Open
Affiliation(s)
- Marcela Carausu
- Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Brussels, Belgium; Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Patrick Neven
- Department of Oncology, Gynecologic Oncology and Multidisciplinary Breast Center, University Hospitals Leuven/KU Leuven, Leuven, Belgium
| | - Michail Ignatiadis
- Université Libre de Bruxelles (ULB), Brussels, Belgium; Department of Medical Oncology, Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium.
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Graff SL, Tinianov S, Kalinsky K. "Nailing down" risk and improving outcomes in early-stage breast cancer. J Natl Cancer Inst 2025; 117:205-208. [PMID: 39576672 DOI: 10.1093/jnci/djae278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 10/29/2024] [Accepted: 10/30/2024] [Indexed: 02/11/2025] Open
Affiliation(s)
- Stephanie L Graff
- Division of Hematology and Oncology, Brown University Health Cancer Center, Providence, RI 02903, United States
- Legorreta Cancer Center, Brown University, Providence, RI 02903, United States
| | - Stacey Tinianov
- Advocates for Collaborative Education, Santa Cruz, CA 95062, United States
| | - Kevin Kalinsky
- Winship Cancer Institute at Emory University, Atlanta, GA 30322, United States
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Tarantino P, Tolaney SM. Progress in breast cancer management. Lancet 2024; 404:1376-1378. [PMID: 39396338 DOI: 10.1016/s0140-6736(24)01823-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 08/29/2024] [Indexed: 10/15/2024]
Affiliation(s)
- Paolo Tarantino
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 022 15, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Oncology and Haemato-Oncology, University of Milan, Milan, Italy
| | - Sara M Tolaney
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 022 15, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
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