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To evaluate the clinical outcomes and relationship between tumor size, lymph node status, and prognosis in a large cohort of patients with confirmed triple receptor-negative breast cancer (TNBC).
We reviewed 1,711 patients with TNBC diagnosed between 1980 and 2009. Patients were categorized by tumor size and nodal status. Kaplan-Meier product limit...
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This study evaluated the outcomes and prognostic factors for breast cancer according to initial lymph node (LN) status. Among patients with LN-negative breast cancer, we also focused on the prognostic value of estrogen receptor (ER) status.
Medical records were retrospectively reviewed for 715 patients who underwent curative surgery for breast canc...
PURPOSE
Breast cancer is the most common cancer in women in India, with higher incidence rates of aggressive subtypes, such as triple-negative breast cancer (TNBC).
METHODS
A systematic review was performed to compute pooled prevalence rates of TNBC among patients with breast cancer, and clinical features at presentation were systematically compar...
Breast cancer incidence is higher among black women than white women before age 40 years, but higher among white women than black women after age 40 years (black-white crossover). We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity.
We classified 91908 inv...
PURPOSE
Estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) are the mainstay of breast cancer management, and their prevalence rates vary among different populations possibly related to ethnic/genetic and/or socioeconomic status. In a previous study conducted at the King Hussein Cancer Center...
Metastatic breast cancers have historically been presumed to have the same predictive biomarkers as the initial primary tumor. We compared the expression of these biomarkers in a large paired tissue microarray (TMA) series of primary and subsequent relapsed tumors.
Using the British Columbia Cancer Agency Breast Cancer Outcomes Unit database, patie...
Citations
... TNBC accounts for 10-15% of breast cancer 5 . It represents the malignant type with high invasive capability, metastatic potential, relapse proneness, fewer treatment options, and a worse prognosis outcome 6 . Currently, systemic therapies, such as chemotherapy, are the main treatment for TNBC. ...
Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive type of breast cancer with a poor prognosis and a high recurrence rate. Chemotherapy is still the mainstay of treatment for cancer patients without a genetic BRCA mutation, despite the approval of Olaparib, an inhibitor of the poly (ADP-ribose) polymerase (PARP) enzyme. Tripartite motif containing-21 (TRIM21) is one of the TRIM family members that has been investigated in various types of cancer. Here, we found that a low TRIM21 expression level was correlated with poor overall survival of TNBC patients. Knockout of TRIM21 promoted the proliferation of TNBC cells in vivo and in vitro, as well as migratory and invasive capabilities in vitro. Importantly, breast cancer susceptibility gene 1 (BRCA1) was identified as a ubiquitination substrate of TRIM21. It was confirmed that BRCA1 was upregulated after Olaparib treatment, which may explain the relative resistance of BRCA1-proficient TNBC cells to Olaparib. Moreover, Sorafenib, a standard treatment for hepatocellular carcinoma, increased the sensitivity of TNBC cells to Olaparib by promoting TRIM21-mediated ubiquitination degradation of BRCA1. Thus, a synergic effect of Olaparib and Sorafenib was found in vitro and in vivo. This combined treatment also aggravated DNA damage, cell cycle arrest, and apoptosis of TNBC cells. In summary, the findings verified the synergistic effect of Olaparib and Sorafenib and revealed TRIM21 as a potential target for TNBC therapy.
... In multiple solid tumors-including breast carcinomas, head and neck carcinomas, colon cancer, and melanoma-the first sites of metastasis are often the tumor-draining lymph nodes (TDLNs; Farnsworth et al., 2018;Jones et al., 2018;du Bois et al., 2021;Zhou et al., 2021). The presence of lymph node metastasis (LNM) is strongly correlated with poor prognosis and guides treatment strategies (Giuliano et al., 2011;Hernandez-Aya et al., 2011;Miranda et al., 2011;Donker et al., 2015;David Nathanson et al., 2020). Recently, we and others independently showed that cancer cells in some LNM could escape the lymph nodes and disseminate to distant organs Pereira et al., 2018), which suggests a critical need to target LNM to prevent local and systemic metastasis in some patients. ...
Tumor-draining lymph nodes (TDLNs) are important for tumor antigen–specific T cell generation and effective anticancer immune responses. However, TDLNs are often the primary site of metastasis, causing immune suppression and worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer cell heterogeneity, plasticity, and immune evasion during breast cancer progression and lymph node metastasis (LNM). A subset of cancer cells in the lymph nodes exhibited elevated MHC class II (MHC-II) gene expression in both mice and humans. MHC-II+ cancer cells lacked costimulatory molecule expression, leading to regulatory T cell (Treg) expansion and fewer CD4+ effector T cells in TDLNs. Genetic knockout of MHC-II reduced LNM and Treg expansion, while overexpression of the MHC-II transactivator, Ciita, worsened LNM and caused excessive Treg expansion. These findings demonstrate that cancer cell MHC-II expression promotes metastasis and immune evasion in TDLNs.
... LN status assessment is important in selecting treatment strategies, predicting therapeutic bene ts, and determining cancer prognosis. As a result, accurate LN metastases diagnosis is critical for cancer patients who are candidates for curative treatment options [2][3][4][5]. Nonetheless, conventional imaging, including CT, MRI and US, still falls to some extent short in diagnosing metastatic LNs [6; 7]. ...
Background
This study was to compare the diagnostic performance, semiquantitative analysis, and staging performance of [¹⁸F]-labelled fibroblast activation protein inhibitor ([¹⁸F]FAPI-42) and 2-[¹⁸F]fluoro-2-deoxy-D-glucose(2-[¹⁸F]FDG) PET/CT in lymph node (LN) metastases.
Methods
From the detection of metastatic LNs, the semiquantitative value of the LN metastases, and the evaluation of N staging, a retrospective analysis of 56 patients diagnosed with LNs metastases who underwent [¹⁸F]FAPI-42 and 2-[¹⁸F]FDG PET/CT scans within a week for staging or restaging was performed. We analyzed, and compared the diagnostic performance and SUVmax of primary tumors and recurrent lesions, as well as the SUVmax, TBR, and diagnostic performance of metastatic LNs between [¹⁸F]FAPI-42 and 2-[¹⁸F]FDG PET/CT.
Results
A total of 216 metastatic LNs from 56 patients were detected and semi-quantitatively analyzed. Compared to 2-[¹⁸F]FDG PET/CT, [¹⁸F]FAPI-42 PET/CT presented a better diagnostic performance based on patients (98.2% vs. 92.9%, P = 0.364), based on lesions (87.5% vs. 78.7%, P = 0.015). Regarding semiquantitative analysis, the SUVmax of LNs metastases on [¹⁸F]FAPI-42 PET/CT presented higher uptake than that on 2-[¹⁸F]FDG PET/CT (SUVmax 5.0 vs. 3.9, P = 0.002). For differentiating metastatic LNs to normal LNs, the SUVmax of [¹⁸F]FAPI-42 in metastatic LNs was significantly higher in the non-metastatic LNs (SUVmax, 5.0 vs. 1.2, P < 0.001). Comparing the management of N staging between two tracers, [¹⁸F]FAPI-42 estimated precisely more patients than 2-[¹⁸F]FDG PET/CT (83.9% vs. 78.4%, P = 0.468).
Conclusion
[¹⁸F]FAPI-42 PET/CT showed superior diagnostic performance, the quantitative capability of metastatic LNs, and the management of N staging in patients with cancers compared to 2-[¹⁸F]FDG PET/CT.
... Besides, 77% of basal-like breast cancer cases are TNBC, which lacks the expression of PR, ER, and HER-2 [4]. TNBC represents the malignant type with high invasive capability, metastatic potential, relapse proneness, fewer treatment options, and a worse prognosis outcome [5]. At presents, systemic therapies, such as chemotherapy, are the primary treatment for TNBC. ...
Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive breast cancer with a poor prognosis and a high recurrence rate. Although Olaparib, a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, was approved for germline BRCA-mutated metastatic breast cancer, chemotherapy remains the mainstay of treatment for cancer patients without BRCA mutation. Tripartite motif containing-21 (TRIM21) is one of the TRIM family members that has been implicated in various types of cancer. This study aimed to investigate the prognostic function of TRIM21. It was found that a low TRIM21 expression level was correlated with a poorer overall survival of TNBC patients. TRIM21 depletion promoted the proliferation of TNBC cells in vivo and in vitro , as well as migratory and invasive capabilities in vitro . Importantly, breast cancer susceptibility gene 1 (BRCA1) was identified as a ubiquitination substrate of TRIM21. It was confirmed that BRCA1 was upregulated after Olaparib treatment, which could explain the relative resistance of TNBC cells without BRCA1 mutation to Olaparib. Moreover, Sorafenib, a standard treatment for hepatocellular carcinoma, increased the sensitivity of TNBC cells to Olaparib through TRIM21-mediated ubiquitination degradation of BRCA1. Thus, a synergic effect of Olaparib and Sorafenib was found in vitro and in vivo . The combined treatment also aggravated DNA damage, cell cycle arrest, and apoptosis of TNBC cells. In summary, the findings verified the synergistic effect of Olaparib and Sorafenib and revealed TRIM21 as a potential target for TNBC therapy.
... Prognosis of stage III triple-negative breast cancer patients is still poor [1,2,3]. In the 1980s-1990s, phase-2 studies supported the concept that patients with metastasized or high-risk primary breast cancer could significantly benefit from chemotherapy dose escalation utilizing autologous stem cell rescue [4,5]. ...
Background
High-dose chemotherapy with autologous stem cell rescue (HDCT) is a promising treatment for patients with stage III, HER2-negative, homologous recombination deficient (HRD) breast cancer. Clinical effectiveness and cost-effectiveness are currently under investigation in an international multicenter randomized controlled trial. To increase the chance of successful introduction of HDCT into daily clinical practice, we aimed to identify relevant factors for smooth implementation using an early comprehensive assessment framework.
Methods
This is a qualitative, multi-stakeholder, exploratory research using semi-structured interviews guided by the Constructive Technology Assessment model, which evaluates the quality of a novel health technology by clinical, economic, patient-related, and organizational factors. Stakeholders were recruited by purposeful stratified sampling and interviewed until sufficient content saturation was reached. Two researchers independently created themes, categories, and subcategories by following inductive coding steps, these were verified by a third researcher.
Results
We interviewed 28 stakeholders between June 2019 and April 2021. In total, five overarching themes and seventeen categories were identified. Important findings for optimal implementation included the structural identification and referral of all eligible patients, early integration of supportive care, multidisciplinary collaboration between- and within hospitals, (de)centralization of treatment aspects, the provision of information for patients and healthcare professionals, and compliance to new regulation for the BRCA1-like test.
Conclusions
In anticipation of a positive reimbursement decision, we recommend to take the highlighted implementation factors into consideration. This might expedite and guide high-quality equitable access to HDCT for patients with stage III, HER2-negative, HRD breast cancer in the Netherlands.
... Bu çalışmada hem lokorejyonel hem de uzak rekürrens oranları beklenen oranlarda izlenmesine rağmen rekürrens ve rekürrenssiz sağkalıma etki eden faktörler te ve çok değişkenli analizlerle incelenmiştir. Çalışmalar ÜNMK hastalarında sağkalım ve hastalıksız sağkalım üzerine tümör boyutu ve nodal tutulumun etkili olduğunu gösterirken, bazıları lenf nodu tutulum sayısının anlamlı olduğunu göstermiştir 12,15 . Sağkalım üzerine tümör boyutu, yaş ve cerrahi metodun etkinliği de çalışmalarda bahsedilmektedir. ...
Amaç: Üçlü negatif meme kanserinde (ÜNMK) hastalık erken evrede tespit edilse de, hastalıksız sağkalım(HSK) ve sağkalım, ÜNMK olmayanlara göre daha düşüktür ve lokal nüks/ uzak metastaz daha erken ortaya çıkma eğilimindedir. Lokal ileri ÜNMK hastalarında neoadjuvan tedavi (NKT) öncelikle tercih edilmektedir. NKT ve tedaviye patolojik tam yanıt (pCR) ise HSK artırmaktadır. Bu çalışma Uludağ Üniversitesi Tıp Fakültesi Meme Cerrahi Kliniğinde ÜNMK tanısı ile ameliyat edilen hastaların lokal rekürrens ve hastalıksız sağkalımına etki eden faktörlerini ortaya konulması amaçlanmıştır. Gereç ve Yöntem: 2007-2020 yılları arasında ameliyat edilen hastaların demografik, klinik, patolojik verileri ve sağkalım oranları retrospektif olarak analiz edildi. İstatistiksel analizler SPSS v23 istatistik programı kullanılarak yapıldı. Bulgular: 173 hastanın 83’ü (%47.7) premenopozal ve yaş ortalaması 49.36+12.29 yıldı. Hastaların 106’sı (%63.8) lokal evre, 59’u(%34.1) lokal ileri evre ve 8’i (%4.6) metastatikti. 101 (%58.4) hastaya neoadjuvant, 69 (%40) hastaya adjuvant kemoterapi verildi. 122 (%70.5) hastaya meme koruyucu cerrahi, 99 (%57.2) hastaya sentinel lenf nodu örneklemesi yapıldı. Genel takip süresi ortanca değeri 57.5 ay içerisinde, 34 (%19.7) hasta yaşamını yitirdi. Ortanca rekürrens zamanı 33 ay içerisinde ise 16 (%11.8) hastada lokal nüks, 39 (%26.6) hastada sistemik nüks izlendi. 3-yıllık hastalıksız sağkalım oranı %47.3 izlendi. Sonuç: ÜNMK’de lokal ve sistemik nüks varlığında hastalıksız sağkalım oranları adjuvant ve neoadjuvant tedavide benzer izlenmiştir. NKT sonrası lokal ve rejyonel rekürrensi artıran ve rekürrenssiz sağkalımı azaltan en önemli faktör N3 hastalık ve premenopozal durum olarak izlenmiştir.
... In recent decades, considerable feats have been achieved in the treatment and survival improvement of BC (31). Some BC subtypes have unique and efficacious treatment methods, for example, HER2-positive BC can be treated with trastuzumabtargeted therapy (32). ...
Pyrimidine metabolism is a hallmark of cancer and will soon become an essential part of cancer therapy. In the tumor microenvironment, cells reprogram pyrimidine metabolism intrinsically and extracellularly, thereby promoting tumorigenesis. Metabolites in pyrimidine metabolism have a significant impact on promoting cancer advancement and modulating immune system responses. In preclinical studies and practical clinical applications, critical targets in pyrimidine metabolism are acted upon by drugs to exert promising therapeutic effects on tumors. However, the pyrimidine metabolism in breast cancer (BC) is still largely underexplored. In this study, 163 credible pyrimidine metabolism-related genes (PMGs) were retrieved, and their somatic mutations and expression levels were determined. In addition, by using The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, 12 PMGs related to the overall survival (OS) were determined using the univariate Cox regression analysis. Subsequently, by performing the LASSO Cox hazards regression analysis in the 12 PMGs in TCGA-BRCA dataset, we developed a prognosis nomogram using eight OS-related PMGs and then verified the same in the METABRIC, GSE96058, GSE20685, GSE42568 and GSE86166 data. Moreover, we validated relationships between the pyrimidine metabolism index (PMI) and the survival probability of patients, essential clinical parameters, including the TNM stage and the PAM50 subtypes. Next, we verified the predictive capability of the optimum model, including the signature, the PAM50 subtype, and age, using ROC analysis and calibration curve, and compared it with other single clinical factors for the predictive power of benefit using decision curve analysis. Finally, we investigated the potential effects of pyrimidine metabolism on immune checkpoints, tumor-infiltrating immune cells, and cytokine levels and determined the potential implications of pyrimidine metabolism in BC immunotherapy. In conclusion, our findings suggest that pyrimidine metabolism has underlying prognostic significance in BC and can facilitate a new management approach for patients with different prognoses and more precise immunotherapy.
... Part of previous research considers axillary metastases as an adverse clinical feature [65,66], especially for short-term survival [67]. The association between nodal status and outcome of TNBC, however, appears not to be straightforward [67,68], while even extensive metastatic disease has not been observed to impair survival [69]. The discrepant and confusing association between nodal status and disease outcome have been linked to the genetic and clinical heterogeneity of TNBC [67]. ...
Purpose
Triple-negative breast cancer (TNBC) is an aggressive disease lacking specific biomarkers to guide treatment decisions. We evaluated the combined prognostic impact of clinical features and novel biomarkers of cell cycle-progression in age-dependent subgroups of TNBC patients.
Methods
One hundred forty seven TNBC patients with complete clinical data and up to 18 year follow-up were collected from Turku University Hospital, Finland. Eight biomarkers for cell division were immunohistochemically detected to evaluate their clinical applicability in relation to patient and tumor characteristics.
Results
Age at diagnosis was the decisive factor predicting disease-specific mortality in TNBC (p = 0.002). The established prognostic features, nodal status and Ki-67, predicted survival only when combined with age. The outcome and prognostic features differed significantly between age groups, middle-aged patients showing the most favorable outcome. Among young patients, only lack of basal differentiation predicted disease outcome, indicating 4.5-fold mortality risk (p = 0.03). Among patients aged > 57, the established prognostic features predicted disease outcome with up to 3.0-fold mortality risk for tumor size ≥ 2 cm (p = 0.001). Concerning cell proliferation, Ki-67 alone was a significant prognosticator among patients aged > 57 years (p = 0.009). Among the studied cell cycle-specific biomarkers, only geminin predicted disease outcome, indicating up to 6.2-fold increased risk of mortality for tumor size < 2 cm (p = 0.03).
Conclusion
Traditional clinical features do not provide optimal prognostic characterization for all TNBC patients. Young age should be considered as an additional adverse prognostic feature in therapeutic considerations. Increased proliferation, as evaluated using Ki-67 or geminin immunohistochemistry, showed potential in detecting survival differences in subgroups of TNBC.
... In cases of broad lymph node involvement, extremely small tumors, according to Wo et al., may represent a more aggressive subtype than larger tumors with equivalent lymph node contribution (28). According to Hernandez-Aya et al. second's study, the number of positive lymph nodes may have no effect on prognosis, independent of tumor size, once there is proof of lymph node contribution, in triplenegative breast cancers (29). Thus, tumor size T1 may correlate to poor clinical outcome or worse prognosis which could explain the lower serum DDX43 protein level. ...
Background: Breast cancer (BC) is the most often diagnosed cancer in women globally. To meet the increased overall protein synthesis and for translation of particular pro-oncogenic mRNAs in order to survive, cancer cells appear to rely heavily on RNA helicases. DDX43 is one of DEAD- box RNA helicase family members. But, the relationship between clinicopathological, prognostic significance, in different BC subtypes and DDX43 expression remains unclear. Our aim therefore is to assess the clinicopathological and prognostic significance in relation to DDX43 protein and mRNA expression.
Materials and Methods: A total of 80 females newly diagnosed with BC and 20 control females, that were age matched, were recruited for this study. DDX43 protein levels were measured by ELISA technique. We used a real-time polymerase chain reaction quantification (real-time PCR) to measure the levels of DDX43 mRNA expression. Levels of DDX43 protein and mRNA expression within BC patients were compared to those of control subjects and correlated with clinicopathological data.
Results: The mean normalized serum levels of DDX43 protein were slightly higher in control than in both benign and malignant groups, but this result was non-significant. The mean normalized level of DDX43 mRNA expression was higher in control than in both benign and malignant cases, although the results were not statistically significant and marginally significant respectively. Moreover, the mean normalized level of DDX43 mRNA expression was significantly higher in benign than in malignant cases. In malignant cases, low DDX43 protein expression was linked to higher nuclear grade and invasive duct carcinoma (IDC), whereas high mRNA expression was linked to a poor prognosis.
Conclusion: Our study explored DDX43 as a cancer marker in human breast cancer. It has the potential to be used in clinical settings as a disease progression marker.
... According to the number and location of axillary lymph node metastases, BC lymph node staging is usually divided into N0, N1, N2, and N3. The higher the stage is, the worse the prognosis 29 . In the past, routine axillary lymph www.nature.com/scientificreports/ ...
The status of axillary lymph node metastases determines the treatment and overall survival of breast cancer (BC) patients. Three-dimensional (3D) assessment methods have advantages for spatial localization and are more responsive to morphological changes in lymph nodes than two-dimensional (2D) assessment methods, and we speculate that methods developed using 3D reconstruction systems have high diagnostic efficacy. This exploratory study included 43 patients with histologically confirmed BC diagnosed at Second Xiangya Hospital of Central South University between July 2017 and August 2020, all of whom underwent preoperative CT scans. Patients were divided into a training cohort to train the model and a validation cohort to validate the model. A 3D axillary lymph node atlas was constructed on a 3D reconstruction system to create various methods of assessing lymph node metastases for a comparison of diagnostic efficacy. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic values of these methods. A total of 43 patients (mean [SD] age, 47 [10] years) met the eligibility criteria and completed 3D reconstruction. An axillary lymph node atlas was established, and a correlation between lymph node sphericity and lymph node metastasis was revealed. By continuously fitting the size and characteristics of axillary lymph nodes on the 3D reconstruction system, formulas and models were established to determine the presence or absence of lymph node metastasis, and the 3D method had better sensitivity for axillary lymph node assessment than the 2D method, with a statistically significant difference in the correct classification rate. The combined diagnostic method was superior to a single diagnostic method, with a 92.3% correct classification rate for the 3D method combined with ultrasound. In addition, in patients who received neoadjuvant chemotherapy (NAC), the correct classification rate of the 3D method (72.7%) was significantly higher than that of ultrasound (45.5%) and CT (54.5%). By establishing an axillary lymph node atlas, the sphericity formula and model developed with the 3D reconstruction system achieve a high correct classification rate when combined with ultrasound or CT and can also be applied to patients receiving NAC.
