RESUMO
Curebest™ 95GC breast (95GC) is a multigene classifier we developed for the prognostic prediction of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and node-negative (ER+/HER2-/n0) invasive breast cancer treated with adjuvant endocrine therapy alone. The aim of the preset study was to evaluate the clinical utility of 95GC in a multiinstitutional registry study. Patients (n=215) with ER+/HER2-/n0 invasive breast cancer who had undergone the 95GC assay in seven hospitals were consecutively recruited in the registry study at various postoperative times. At recruitment, no patients had disease recurrences and were prospectively followed up for a median of 62 (range, 6-91) postoperative months. Of the 124 patients classified as 95GC low risk, 118 received adjuvant endocrine therapy alone and six received adjuvant chemo-endocrine therapy. Only two patients developed distant recurrences, and the 5-year distant recurrence-free survival (DRFS) was as high as 98.0%. Of the 91 patients classified as 95GC high risk, 81 received adjuvant chemo-endocrine therapy and 10 received adjuvant endocrine therapy alone. A total of four of these patients developed distant recurrences (5-year DRFS=95.5%). Among the 95GC high-risk patients, prognosis was significantly improved for the 81 treated with adjuvant chemo-endocrine therapy compared with for the 77 (historical controls) treated with adjuvant endocrine therapy alone (P=0.0002; hazard ratio, 0.24). Compared with the St. Gallen 2013 guideline, a significant de-escalation from 73.1% (155/212) to 40.6% (86/212) in adjuvant chemotherapy was achieved. The excellent prognosis of patients with ER+/HER2-/n0 invasive breast cancer classified as 95GC low risk could be validated in the present registry study, indicating that 95GC is useful for safe de-escalation of adjuvant chemotherapy in patients with ER+/HER2-/n0 invasive breast cancer.
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Neoplasias da Mama , Feminino , Humanos , Recidiva Local de Neoplasia , Análise de SobrevidaRESUMO
BACKGROUND: The one-step nucleic acid amplification (OSNA) assay can quantify the cytokeratin 19 messenger RNA copy number as a proxy for sentinel lymph node (SN) metastasis in breast cancer. A large-scale, multicenter cohort study was performed to determine the prognostic value of the SN tumor burden based on a molecular readout and to establish a model for the prediction of early systemic recurrence in patients using the OSNA assay. METHODS: SN biopsies from 4757 patients with breast cancer were analyzed with the OSNA assay. The patients were randomly assigned to the training or validation cohort at a ratio of 2:1. On the basis of the training cohort, the threshold SN tumor burden value for stratifying distant recurrence was determined with Youden's index; predictors of distant recurrence were investigated via multivariable analyses. Based on the selected predictors, a model for estimating 5-year distant recurrence-free survival was constructed, and predictive performance was measured with the validation cohort. RESULTS: The prognostic cutoff value for the SN tumor burden was 1100 copies/µL. The following variables were significantly associated with distant recurrence and were used to construct the prediction model: SN tumor burden, age, pT classification, grade, progesterone receptor, adjuvant cytotoxic chemotherapy, and adjuvant anti-human epidermal growth factor receptor 2 therapy. The values for the area under the curve, sensitivity, specificity, and accuracy of the prediction model were 0.83, 63.4%, 81.7%, and 81.1%, respectively. CONCLUSIONS: Using the OSNA assay, the molecular readout-based SN tumor burden is an independent prognostic factor for early breast cancer. This model accurately predicts early systemic recurrence and may facilitate decision-making related to treatment.
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Neoplasias da Mama , Linfonodo Sentinela , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Estudos de Coortes , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Patologia Molecular , Linfonodo Sentinela/patologiaRESUMO
The diagnostic accuracy of the multigene panel test (MPT) and OncoScan™ in the determination of HER2 amplification in breast tumors remains controversial. In the present study, HER2 copy number was analyzed using both MPT and OncoScan™ in 45 breast tumors and was compared with that in fluorescent in situ hybridization (FISH) analysis. Tumors with low cellularity were examined using tumor cell enrichment and fluorescenceactivated cell sorting. Both MPT and OncoScan™ exhibited significant correlations with FISH with respect to the determination of HER2 amplification in breast tumors. However, the correlation coefficient was significantly higher for the comparison of MPT and FISH (r=0.770) compared with that between OncoScan™ and FISH (r=0.564). The accuracy of MPT (93.3%) was slightly higher compared with that in OncoScan™ (84.4%) in determining the HER2 status, which was mostly explained by the higher sensitivity of MPT in tumors with low cellularity (83.3 vs. 33.3%), but not in those with high cellularity (81.8 vs. 72.7%). The specificity was 100% for both tests. The MPT exhibited higher sensitivity in the determination of the amplification of other genes, including MYC, fibroblast growth factor receptor 1 and GATA binding protein 3 in tumors with low cellularity compared with that in tumors with high cellularity. OncoScan™ exhibited low sensitivity without tumor cell enrichment. The results suggested that MPT could be a promising method to determine HER2 status in breast tumors and that it could exhibit improved accuracy compared with that in OncoScan™ in tumors with low cellularity.
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Neoplasias da Mama/genética , Análise Mutacional de DNA/métodos , Amplificação de Genes/genética , Genes erbB-2/genética , Hibridização in Situ Fluorescente/métodos , Receptor ErbB-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismoRESUMO
PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.
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Neoplasias da Mama , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Feminino , Perfilação da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/genética , Prognóstico , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Estudos RetrospectivosRESUMO
We aimed to validate the cosmetic utility of addition of nipple-areola recentralization (NAR) to rotation flap according to nipple tumor distance (NTD) as a volume displacement technique after breast conserving surgery (BCS) for lower-outer and upper-inner breast cancers. Twenty breast cancer patients who had been treated with rotation flap with (Group 1; nâ¯=â¯6) or without (Group 2; nâ¯=â¯14) NAR after BCS for lower-outer or upper-inner located tumors, and those who had undergone BCS without oncoplastic surgical technique for tumors in the same area (Control group; nâ¯=â¯43), were retrospectively investigated. Cosmetic outcome was evaluated using Harvard scale and/or BCCT.core. As a result, the ratio of patients categorized as excellent/good was 83% in Group 1 and 93% in Group 2, respectively, and there was no significant difference between them (Pâ¯=â¯0.521). In addition, Group 1â¯+â¯2 showed a significantly higher ratio of patients classified as excellent/good than the control group (90% vs. 56%; Pâ¯=â¯0.009). After adjustment of clinical background parameters using propensity score matching analysis between Group 1â¯+â¯2 and the control group, 12 pairs with similar background factors were matched. Among them, Group 1â¯+â¯2 showed a higher ratio of patients categorized as excellent/good than the control group (92% vs. 42%; Pâ¯=â¯0.034). In conclusion, addition of NAR to rotation technique according to NTD may enable us to perform a volume displacement after BCS for lower-outer or upper-inner located tumors irrespective of NTD without sacrificing postoperative breast appearance.
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Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar , Mamilos/cirurgia , Retalhos Cirúrgicos/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estética , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Satisfação do Paciente/estatística & dados numéricos , Pontuação de Propensão , Estudos RetrospectivosRESUMO
HER2 amplification is seen in 20-25% of primary breast cancer cases, and HER2 detection is performed routinely in primary operable, as well as metastatic breast cancer patients. Currently, HER2 is the only gene of which amplification is routinely assayed by fluorescent in situ hybridization (FISH) and/or immunohistochemistry (IHC). However, histochemical assay (FISH/IHC) of multiple target genes is laborious and time-consuming, and simultaneous amplification by microarray is preferred. OncoScan™ is a microarray-based assay capable of whole-genome copy number analysis using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues. In the current study, we aimed to investigate the impact of tumor cellularity on the accuracy of OncoScan™ in the determination of HER2 amplification. Our results demonstrated that HER2 amplification by OncoScan™ is accurate, and has a high concordance rate of 93.3% with FISH. However, the concordance rate is poor (66.7%) in cases with a tumor cellularity < 20%. Nevertheless, the addition of FISH to breast tumors with a tumor cellularity < 20% and a HER2 copy number of 4 appears to be useful to minimize false-negative results by OncoScan™.
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Neoplasias da Mama/genética , Amplificação de Genes , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Receptor ErbB-2 , Estudos Retrospectivos , Análise Serial de Tecidos/instrumentação , Análise Serial de Tecidos/normasRESUMO
In clinical decision-making, to decide the indication for adjuvant chemotherapy for estrogen receptor-positive (ER+), human epidermal growth factor receptor-2-negative (HER2-), and node-negative (n0) breast cancer patients, the accurate estimation of recurrence risk is essential. Unfortunately, conventional prognostic factors, such as tumor size, histological grade and ER, progesterone receptor (PR), and HER2 status as well as Ki67 index, are not sufficiently accurate for such estimation. Therefore, several multigene assays (MGAs) based on the mRNA expression analysis of multiple genes in tumor tissue have been developed to better predict patient prognosis. These assays include Oncotype DX, MammaPrint, PAM50, GGI, EndoPredict, and BCI. We developed Curebest™ 95-Gene Classifier Breast (95GC) classifier, which is unique in that mRNA expression data of all 20 000 human genes are secondarily obtainable, as the 95GC assay is performed using Affymetrix microarray. This can capture mRNA expression of not only 95 genes but also every gene at once, and such gene expression data can be utilized by the other MGAs that we have developed, such as the 155GC, which is used for the prognostic prediction of ER+/HER2- breast cancer patients treated with neoadjuvant chemotherapy. We also developed the 42GC for predicting late recurrence in ER+/HER2- breast cancer patients. In this mini-review, our recent attempt at the development of various MGAs, which is expected to facilitate the implementation of precision medicine in ER+/HER2- breast cancer patients, is presented with a special emphasis on 95GC.
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Neoplasias da Mama/genética , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Medicina de Precisão/métodos , Prognóstico , RNA Mensageiro/genética , Receptores de Progesterona/genéticaRESUMO
Ten stage I/II breast cancer patients with one or two suspicious lymph nodes (LNs) detected on ultrasonography underwent sentinel LN biopsy (SLNB) after the introduction of Twirl® breast markers into each suspicious LN revealed that each Twirl®-marked LN was SLN and was likely the first SLN. Three patients had less than three SLN metastases and were candidates for sparing completion axillary lymph node dissection (cALND). Indeed, of them, one underwent breast-conserving surgery without cALND and the other two underwent total mastectomy with cALND. These results suggest that, as all suspicious LNs are SLNs, patients can be treated with SLNB alone if they fulfill the ACOSOG Z-0011 criteria, despite suspicious LNs yielding positive results on preoperative fine-needle aspiration cytology.
Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico , Biópsia de Linfonodo Sentinela/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Feminino , HumanosRESUMO
Humoral immunity plays a substantial role in the suppression of breast cancer. We have revealed that a high serum concentration of anti-HER2 autoantibody (HER2-AAb) is associated with favorable outcomes in patients with invasive breast cancer. Thus, we aimed to clarify the association between high serum concentration of HER2-AAb and humoral immune response in the tumor microenvironment. Out of 500 consecutive patients with invasive breast cancer, we selected those whose HER2-AAb values were high (n = 33) or low (n = 20) based on the distribution of HER2-AAb values of 100 healthy individuals. Tumor and regional lymph node formalin-fixed paraffin-embedded samples prepared from the surgical specimens were subjected to immunohistochemistry. We confirmed that the recurrence-free survival of the high HER2-AAb group was significantly longer than that of the low HER2-AAb group (p = 0.015). The numbers of tumor-infiltrating CD20+ immune cells (ICs) (p < 0.001), IGKC+ICs (p = 0.023), and CXCL13+ ICs (p = 0.044) were significantly higher in the high HER2-AAb group than in the low HER2-AAb group. The number of CD4+ ICs in the B-cell follicles of the regional lymph nodes was also significantly greater in the high HER2-AAb group than in the low HER2-AAb group (p = 0.026). Our findings indicate that a high level of HER2-AAb is associated with enhanced humoral immunity against breast cancer and thus may provide a rationale for the association of HER2-AAb with favorable prognosis.
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Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/imunologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Lobular/imunologia , Receptor ErbB-2/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/sangue , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Imunidade Humoral/imunologia , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: The aim of our study is to find microRNAs (miRNAs) associated with sentinel lymph node metastasis (SLNM) and to develop a prediction model for SLNM in ER-positive and HER2-negative (ER+/HER2-) breast cancer. PATIENTS AND METHODS: In the present study, only ER+/HER2- primary breast cancer was considered. The discovery set for SLNM-associated miRNAs included 10 tumors with and 10 tumors without SLNM. The training and validation sets both included 100 tumors. miRNA expression in tumors was examined comprehensively by miRNA microarray in the discovery set and by droplet digital PCR in the training and validation sets. RESULTS: In the discovery set, miR-98, miR-22, and miR-223 were found to be significantly (P < 0.001, fold-change > 2.5) associated with SLNM. In the training set, we constructed the prediction model for SLNM using miR-98, tumor size, and lymphovascular invasion (LVI) with high accuracy (AUC, 0.877). The accuracy of this prediction model was confirmed in the validation set (AUC, 0.883), and it outperformed the conventional Memorial Sloan Kettering Cancer Center nomogram. In situ hybridization revealed the localization of miR-98 expression in tumor cells. CONCLUSIONS: We developed a prediction model consisting of miR-98, tumor size, and LVI for SLNM with high accuracy in ER+/HER2- breast cancer. This model might help decide the indication for SLN biopsy in this subtype.
Assuntos
Neoplasias da Mama , MicroRNAs , Linfonodo Sentinela , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Humanos , Linfonodos , Metástase Linfática , MicroRNAs/genética , Nomogramas , Curva ROC , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo SentinelaRESUMO
Recent studies demonstrated that homologous repair deficiency (HRD) score is a useful marker for response to poly (ADP-ribose) polymerase inhibitors or platinum-based chemotherapy. We determined HRD scores and elucidated the clinicopathologic characteristics of HRD-high tumors and their response to non-platinum-based chemotherapy. Primary breast cancer patients (nâ¯=â¯120) were pre-operatively treated with paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC). Germline and somatic homologous recombination related gene mutations (gHRRm and sHRRm, respectively) and HRD scores were analyzed using whole exome sequencing (WES) in tumor tissues obtained before chemotherapy. Of 120 tumors, 30 were determined to be HRD-high tumors, significantly associated with high Ki-67 (Pâ¯=â¯0.014), ER negativity (Pâ¯=â¯0.007), and PR negativity (Pâ¯=â¯0.021). Triple-negative cancers showed significantly higher HRD scores than the luminal, luminal-HER2, and HER2 subtypes (Pâ¯=â¯0.023, 0.016, and 0.033, respectively). HRD scores were significantly higher in tumors with gHRRm than in those with sHRRm (Pâ¯=â¯0.002) or wild-type HRR genes (Pâ¯=â¯1.44e-4), but no significant difference was found in HRD scores between tumors with sHRRm and wild-type HRR genes (Pâ¯=â¯0.206). HRD-high tumors had significantly (Pâ¯=â¯0.003) higher pCR rates and higher near-pCR rates (Pâ¯=â¯0.049) compared with those of the HRD-low tumors in all tumors and the luminal subtype, respectively. HRD-high tumors were associated with aggressive phenotypes and gHRRm, but not sHRRm. Our findings suggested that HRD scores might be useful in predicting response to P-FEC in the luminal subtype.
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BACKGROUND/AIM: Magnetic resonance imaging (MRI)-guided breast biopsy is a complex and time-consuming procedure. This study aimed to clarify the factors that affect the duration of the procedure. PATIENTS AND METHODS: Twenty-eight examinations performed at our institute for 27 lesions detected solely on MRI were analyzed. The correlations between the clinicopathological factors and duration of the procedure were estimated. RESULTS: The needle guidance method was the only factor that significantly affected the duration of the MRI-guided vacuum-assisted breast biopsy (VAB) (p=0.012). The use of a computer-aided detection (CAD) system with grid breast compression plates had significantly shorter durations (62±12 min) than the manual calculation of coordinates with pillar-type compression plates (76±13 min). CONCLUSION: This preliminary study showed that the use of a CAD system might shorten the duration of MRI-guided VAB.
Assuntos
Neoplasias da Mama/diagnóstico , Mama/diagnóstico por imagem , Biópsia Guiada por Imagem , Imagem por Ressonância Magnética Intervencionista , Adulto , Idoso , Biópsia por Agulha/métodos , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Tempo , VácuoAssuntos
Neoplasias da Mama , Linfonodo Sentinela , Axila , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , MicroRNAs/genética , Nomogramas , Curva ROC , Receptor ErbB-2 , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo SentinelaRESUMO
Clean surgical margins in breast-conserving surgery (BCS) are essential for preventing recurrence. Intraoperative pathologic diagnostic methods, such as frozen section analysis and imprint cytology, have been recognized as crucial tools in BCS. However, the complexity and time-consuming nature of these pathologic procedures still inhibit their broader applicability worldwide. To address this situation, two issues should be considered: 1) the development of nonpathologic intraoperative diagnosis methods that have better sensitivity, specificity, speed, and cost; and 2) the promotion of new imaging algorithms to standardize data for analyzing positive margins, as represented by artificial intelligence (AI), without the need for judgment by well-trained pathologists. Researchers have attempted to develop new methods or techniques; several have recently emerged for real-time intraoperative management of breast margins in live tissues. These methods include conventional imaging, spectroscopy, tomography, magnetic resonance imaging, microscopy, fluorescent probes, and multimodal imaging techniques. This work summarizes the traditional pathologic and newly developed techniques and discusses the advantages and disadvantages of each method. Taking into consideration the recent advances in analyzing pathologic data from breast cancer tissue with AI, the combined use of new technologies with AI algorithms is proposed, and future directions for real-time intraoperative margin assessment in BCS are discussed.
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We attempted to detect circulating tumor DNA (ctDNA), taking advantage of molecular barcode next-generation sequencing (MB-NGS), which can be more easily customized to detect a variety of mutations with a high sensitivity than PCR-based methods. Sequencing with a gene panel consisting of the 13 most frequently mutated genes in breast tumors from stage I or II patients revealed 95 somatic mutations in the 12 genes in 62% (62/100) of tumors. Then, plasma DNA from each patient (n = 62) before surgery was analyzed via MB-NGS customized to each somatic mutation, resulting in the detection of ctDNA in 16.1% (10/62) of patients. ctDNA was significantly associated with biologically aggressive phenotypes, including large tumor size (P = .004), positive lymph node (P = .009), high histological grade (P < .001), negative ER (P = .018), negative PR (P = .017), and positive HER2 (P = .046). Furthermore, distant disease-free survival was significantly worse in patients with ctDNA (n = 10) than those without ctDNA (n = 52) (P < .001). Our results demonstrate that MB-NGS personalized to each mutation can detect ctDNA with a high sensitivity in early breast cancer patients at diagnosis, and it seems to have a potential to serve as a clinically useful tumor marker for predicting their prognosis.
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To examine the correlation of qualitative and quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) results with 95-gene classifier or Curebest 95-gene classifier Breast (95GC) results for recurrence prediction in estrogen receptor-positive breast cancer (ERPBC).This retrospective study included 78 ERPBC patients (age range, 24-74 years) classified into high- (nâ=â33) and low- (nâ=â45) risk groups for recurrence based on 95GC and who underwent DCE-MRI between July 2006 and November 2012. For qualitative evaluation, mass shape, margin, and internal enhancement based on BI-RADS MRI lexicon and multiplicity were determined by consensus interpretation by 2 breast radiologists. For quantitative evaluation, mass size, volume ratios of the DCE-MRI kinetics, and both the kurtosis and the skewness of the intensity histogram for the whole mass in the initial and delayed phases were determined. Differences between the 2 risk-groups were analyzed using univariate logistic regression analyses and multiple logistic regression analyses. Receiver-operating characteristic curve cut-off values were used to define the groups.As for the qualitative findings, the difference between the 2 groups was not significant. For the quantitative data, the volume ratio of "medium" in the initial phase differed significantly between the 2 groups (Pâ=â.049). The volume ratio of "medium" (Pâ=â.006) and of "slow-persistent" (Pâ=â.005), and the delayed phase kurtosis (Pâ=â.012) in the univariate logistic regression analyses, and in the multiple logistic regression, volume ratio of "medium" >38.9% and delayed phase kurtosis >3.31 were identified as significant high-risk indicators (odds ratio, 5.83 and 3.55; 95% confidence interval, 1.58 to 21.42 and 1.24 to 10.15; Pâ=â.008 and Pâ=â.018, respectively).A high volume ratio of "medium" in the initial phase and/or high kurtosis in the delayed phase for quantitative evaluation could predict high ERPBC recurrence risk based on 95GC.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Diagnóstico por Computador , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptores de Estrogênio , Estudos Retrospectivos , Medição de Risco/métodos , Adulto JovemRESUMO
ESR1 mutations in breast cancer are known as one of the mechanisms of resistance to aromatase inhibitors. These mutations often occur in the hotspot regions in the ligand binding domain (LBD), but comprehensive mutational analysis has shown that mutations are observed throughout the whole LBD. We previously developed a molecular barcode sequencing (MB-NGS) technique to detect ESR1 hotspot mutations in plasma with high sensitivity. In this study, we have developed a multiplex MB-NGS assay that covers the whole LBD of ESR1. The assay demonstrated that the background errors in the plasma DNA of 10 healthy controls were below 0.1%; thus, the limit of detection was set at 0.1%. We analyzed the plasma DNA of 54 patients with estrogen receptor-positive metastatic breast cancer. Seventeen mutations were detected in 13 patients (24%), with variant allele frequencies ranging from 0.13% to 10.67%, including six rare mutations with a variant allele frequency <1.0% and a novel nonhotspot mutation (A312V). Three patients had double mutations located in the same amplicons, and it was revealed that the double mutations were located in different alleles. ESR1 hotspot mutations were associated with a longer duration of aromatase inhibitor treatment under metastatic conditions and to liver metastasis. The multiplex MB-NGS assay is useful for the sensitive and comprehensive detection of mutations throughout the whole LBD of ESR1. Our assay can be applied to any specific target region of interest using tailor-made primers and can result in minimized sequencing volume and cost.
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AIM: To investigate the feasibility of hookwire-guided sentinel lymph node biopsy (SLNB) using contrast-enhanced ultrasonography (CEUS) followed by a one-step nucleic acid amplification (OSNA) assay. PATIENTS AND METHODS: Clinical T1-2N0M0 breast cancer patients scheduled to undergo SLNB participated in this study. Both Sonazoid® and dye were used as tracers, and the most upstream sentinel lymph node (SLN) at each lymphatic flow detected by CEUS (First-SLN) was sampled under hookwire guidance, a procedure called "Sona-Hook". RESULTS: In each of the 50 cases, at least one First-SLN was extracted by "Sona-Hook". All contrast-enhanced SLNs (CE-SLNs) were dye-positive, and the mean number of CE-SLNs sampled per patient was lower than that of dye-positive SLNs (1.48 vs. 1.88, p<0.01). Through OSNA, qualitative assessment of tumor metastasis between First-SLNs and all SLNs completely matched together. CONCLUSION: "Sona-Hook" for First-SLN followed by an OSNA assay may be a feasible minimally invasive SLNB strategy.
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Neoplasias da Mama/patologia , Meios de Contraste , Biópsia Guiada por Imagem/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Linfonodo Sentinela/patologia , Ultrassonografia Mamária/métodos , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/genética , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Prognóstico , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgiaRESUMO
Onestep nucleic acid amplification (OSNA) targeting cytokeratin 19 (CK19) mRNA expression and pathological examination are widely used for the intraoperative diagnosis of sentinel node (SN) metastasis. The aim of the present study was to develop a novel assay for detecting SN metastasis by targeting Ras association domaincontaining protein 1 (RASSF1A) methylation in tumor cells, and to compare its performance with OSNA. Using digital PCR with methylationspecific restriction enzymes (REdMSP), our assay was able to detect ≥3 copies of methylated DNA per well, and was ≥10 times more sensitive than realtime PCR with bisulfite modification. OSNA lysates were examined using REdMSP and digital PCR for PIK3CA mutation, in the event that primary tumors were PIK3CA mutationpositive. REdMSP revealed a high concordance of 95.0% (153/161) with OSNA, and 100% (59/59) with PIK3CA mutation for detecting SN metastasis. In 11 breast cancer cell lines, the variation in methylated RASSF1A copy number was significantly lower than that of CK19 mRNA (2.8 vs. 10.5fold; P<0.01). REdMSP has the potential to more accurately detect SN metastasis, and to more precisely estimate total tumor loads in SN, compared with OSNA.