Background:Hereditary breast cancer comprises 5–10% of all breast cancers. Mutations in two high-risk susceptibility genes, BRCA1 and BRCA2, along with rare intermediate-risk genes and common low-penetrance alleles identified, altogether explain no more than 45% of the high-risk breast cancer families, although the majority of cases are unaccounted for and are designated as BRCAX tumours. Micro RNAs have called great attention for classification of different cancer types and have been implicated in a range of important biological processes and are deregulated in cancer pathogenesis.Methods:Here we have performed an exploratory hypothesis-generating study of miRNA expression profiles in a large series of 66 primary hereditary breast tumours by microarray analysis.Results:Unsupervised clustering analysis of miRNA molecular profiles revealed distinct subgroups of BRCAX tumours, ‘normal-like' BRCAX-A, ‘proliferative' BRCAX-B, ‘BRCA1/2-like' BRCAX-C and ‘undefined' BRCAX-D subgroup. These findings introduce a new insight in the biology of hereditary breast cancer, defining specific BRCAX subgroups, which could help in the search for novel susceptibility pathways in hereditary breast cancer.Conclusion:Our data demonstrate that BRCAX hereditary breast tumours can be sub-classified into four previously unknown homogenous groups characterised by specific miRNA expression signatures and histopathological features.
BACKGROUND.The prognostic significance of the presence of a neuroendocrine marker (synaptophysin, SY) was analyzed in stage I of squamous carcinoma and adenocarcinoma of the lung.METHODS.A multicentric retrospective study was conducted with immunohistochemical staining in a single center of 318 patients resected for squamous carcinoma or adenocarcinoma in pathologic stage I.RESULTS.In all, 162 cases of squamous carcinoma and 156 cases of adenocarcinoma were identified, which included 105 patients in stage IA (50 patients with squamous carcinoma and 55 patients with adenocarcinoma) and 213 in stage IB (112 with squamous carcinoma and 101 with adenocarcinoma). Eighty‐six tumors showed a presence of SY+ (27%). Univariate analysis showed lower survival rates at 5 years for those patients older than 70 years of age compared with those patients younger than 70 years of age (60.35% vs 70.57%; P = .007) and for those patients with SY+ compared with those with SY− (52.48% vs 72.68%; P = .0017). Patients with SY+ tumors showed a higher rate of recurrence than patients with SY− tumors (50% vs 33.6%; P = .008). Multivariate analysis showed that those patients greater that 70 years of age (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.14–2.65) and the presence of SY (HR, 2.15; 95% CI, 1.40–3.30) were significant independent prognostic factors associated with a poor outcome.CONCLUSIONS.Stage I of squamous carcinoma and adenocarcinoma of the lung with SY+ has a poor prognosis, with a higher frequency of recurrence and lower survival rates. Cancer 2007. © 2007 American Cancer Society.
PURPOSE Genetic heterogeneity between primary tumors and their metastatic lesions has been documented in several breast cancer studies. However, the selection of therapy for patients with metastatic breast cancer and the search for biomarkers for targeted therapy are often based on findings from the primary tumor, mainly because of the difficulty of distant metastasis core biopsies. New methods for monitoring genomic changes in metastatic breast cancer are needed (ie, circulating tumor DNA [ctDNA] genomic analysis). The objectives of this study were to assess the concordance of genomic variants between primary and metastatic tumor tissues and the sensitivity of plasma ctDNA analysis to identify variants detected in tumor biopsies. PATIENTS AND METHODS Next-generation sequencing technology was used to assess the genomic mutation profile of a panel of 54 cancer genes in matched samples of primary tumor, metastatic tumor, and plasma from 40 patients with metastatic breast cancer. RESULTS Using Ion Torrent technology (ThermoFisher Scientific, Waltham, MA), we identified 110 variants that were common to the primary and metastatic tumors. ctDNA analysis had a sensitivity of 0.972 in detecting variants present in both primary and metastatic tissues. In addition, we identified 13 variants in metastatic tissue and ctDNA not present in primary tumor. CONCLUSION We identified genomic variants present in metastatic biopsies and plasma ctDNA that were not present in the primary tumor. Deep sequencing of plasma ctDNA detected most DNA variants previously identified in matched primary and metastatic tissues. ctDNA might aid in therapy selection and in the search for biomarkers for drug development in metastatic breast cancer.
Background: HER2DX (Prat et al. EBiomedicine 2022) is a 27-gene prognostic (risk-score) and predictive (pathological complete response [pCR]-score) assay in early-stage HER2+ breast cancer based on clinical data and the expression of 4 gene signatures (immune, proliferation, luminal differentiation and HER2 amplicon). Here, we aim to evaluate, for the first time, the ability of HER2DX to predict pCR following neoadjuvant TCH or TCHP in HER2+ disease. Methods: Standardized HER2DX was performed in a central lab on baseline pre-treatment FFPE tumor biopsies from the GOM-HGUGM-2018-05 study in Spain, a consecutive retrospective series of patients (pts) with newly diagnosed stage I-III HER2+ breast cancer eligible for neoadjuvant therapy. Pts received standard 6 cycles of docetaxel, carboplatin and trastuzumab (TCH) or TCH with pertuzumab (TCHP) regimens. Primary aim was to test the ability of HER2DX pCR score to predict pCR (ypT0/is ypN0). Secondary objectives were to test the ability of HER2DX pCR score to predict pCR independently of clinical-pathological variables and the PAM50 subtype (HER2-enriched versus not), and to evaluate the association of HER2DX pCR score with the HER2DX risk-score. Logistic regression and receiver-operator curve (ROC) analysis were assessed. Statistical analyses were performed in R code 4.0.5. Results: HER2DX was evaluated in 155 pts (97%) enrolled in the study with available RNA (as of June 2022). Mean age of pts was 50 (range 22-74) and 55.2% of pts (n=85) were pre-menopausal. Clinical T2-4 disease represented 77.4% of cases (n=120), clinical node-positive disease (cN1-3) represented 63.9% of cases (n=99), and 68.0% of tumors (n=105) were hormone receptor-positive. The overall pCR rate was 57.4% (95% confidence interval [CI] 50-65): 52.2% (95% CI 40-64) with TCH (n=67) and 61.4% (95% CI 50-72) with TCHP (n=88). The proportion of HER2DX low-, medium- and high-pCR groups was 34.2%, 34.8% and 31.0%, respectively. HER2DX pCR score (as a continuous variable from 0 to 100) was significantly associated with pCR (odd ratio [OR]=1.03, p=5.91e-07). The pCR rates in HER2DX pCR-high and pCR-low groups were 75.0% and 28.0% (OR=7.6, 95% CI 3.2-19.1, p=7.14e-06), respectively. In pts treated with TCHP, the pCR rates in HER2DX pCR-high and pCR-low groups were 85.7% and 27.3% (OR=16.0, 95% CI 4.3-59.01, p=3.2e-05), respectively. The AUC ROC of HER2DX pCR score (as a continuous variable) and pCR status was 0.746 (in all pts) and 0.812 (in pts treated with TCHP). HER2DX pCR score was significantly associated with pCR independently of hormone receptor status, Ki67, age, menopausal status, pertuzumab use, clinical stage and PAM50 HER2-enriched subtype. The proportion of HER2DX low- and high-risk of relapse disease was 32.0% and 68.0%, respectively. The correlation of HER2DX pCR score and HER2DX risk-score was weak (coefficient=-0.17), as previously described. Proportion of cases according to both HER2DX scores and absolute difference of pCR rates between TCHP and TCH in each combined group is shown in Table. Conclusion: The HER2DX genomic test predicts pCR following neoadjuvant TCH or TCHP regimens independently of clinical-pathological variables and intrinsic subtype. The combination of both HER2DX scores might help better tailor systemic therapy in patients with newly diagnosed stage I-III HER2+ breast cancer. Citation Format: Coralia Bueno-Muiño, Isabel Echavarria, Sara López-Tarruella, Roche-Molina Marta, María del Monte-Millán, Tatiana Massarrah, Yolanda Jerez Gilarranz, Blanca Herrero, Salvador Gámez, Iván Márquez-Rodas, María Cebollero-Presmanes, Nevado Santos Manuel, Pilar de la Morena Barrio, Francisco Ayala de la Peña, José Ángel García-Sáenz, Fernando Moreno Antón, Álvaro Rodríguez Lescure, Teresa Quintanar, Diego Malón-Giménez, Laura Rodriguez-Lajusticia, Ana Isabel Ballesteros García, Dulce Bañón Torres, Lucía Villarejo, Nerea Lobato, Ainhoa Arias, Inmaculada Ocaña, Enrique Álvarez, Laia Paré, Mercedes Marín-Aguilera, Patricia Galván, Fara Brasó-Maristany, Ana Vivancos, Patricia Villagrasa, Joel S Parker, Charles M. Perou, Aleix Prat, Miguel Martín. Independent validation of the HER2DX genomic test in HER2-positive breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab +/- pertuzumab (TCH/TCHP): a correlative analysis from a multicenter academic study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-46.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.