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1.
Am J Surg Pathol ; 47(2): 172-182, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36638314

ABSTRACT

Core needle biopsy (CNB) of breast lesions is routine for diagnosis and treatment planning. Despite refinement of diagnostic criteria, the diagnosis of breast lesions on CNB can be challenging. At many centers, including ours, confirmation of diagnoses rendered in other laboratories is required before treatment planning. We identified CNBs first diagnosed elsewhere that were reviewed in our department over the course of 1 year because the patients sought care at our center and in which a change in diagnosis had been recorded. The outside and in-house CNB diagnoses were then classified based on Breast WHO Fifth Edition diagnostic categories. The impact of the change in diagnosis was estimated based on the subsequent surgical management. Findings in follow-up surgical excisions (EXCs) were used for validation. In 2018, 4950 outside cases with CNB were reviewed at our center. A total of 403 CNBs diagnoses were discrepant. Of these, 147 had a change in the WHO diagnostic category: 80 (54%) CNBs had a more severe diagnosis and 44 (30%) a less severe diagnosis. In 23 (16%) CNBs, the change of diagnostic category had no impact on management. Intraductal proliferations (n=54), microinvasive carcinoma (n=18), and papillary lesions (n=35) were the most disputed diagnoses. The in-house CNB diagnosis was confirmed in most cases with available excisions. Following CNB reclassification, 22/147 (15%) lesions were not excised. A change affecting the surgical management at our center occurred in 2.5% of all CNBs. Our results support routine review of outside breast CNB as a clinically significant practice before definitive treatment.


Subject(s)
Breast Neoplasms , Breast , Humans , Female , Biopsy, Large-Core Needle , Tertiary Care Centers , Retrospective Studies , Breast/surgery , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Breast Neoplasms/etiology
2.
Histopathology ; 82(2): 242-253, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36130728

ABSTRACT

Thyroid transcription factor 1 (TTF1) and p40 are widely-utilized diagnostic markers of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), respectively. Diffuse coexpression of TTF1 and p40 has been described in only rare case reports. In a multi-institutional study, we collected the largest cohort of these unusual tumours to-date (n = 14), with the goal of elucidating their clinicopathological and genomic characteristics. Lung tumours with diffuse coexpression (labelling 50-100% tumour cells) of TTF1 clone 8G7G3/1 and p40 clone BC28 were identified. Detailed clinicopathological and immunohistochemical parameters were analyzed. Eight tumours were analyzed by next-generation sequencing (NGS) and the results were compared to those in > 9 K LUAD and > 1 K LUSC. All tumours with diffuse TTF1/p40 coexpression were poorly differentiated non-small cell lung carcinomas (NSCLC), 42% of which had basaloid features. Some tumours exhibited focal keratinization (14%), napsin A and/or mucicarmine labelling (46%) or both squamous and glandular features (7%). NGS revealed a uniquely high rate of FGFR1 amplifications (70%) compared to either LUAD (0.7%, P < 0.0001) or LUSC (11%, P = 0.001). LUAD-type targetable driver alterations were identified in 38% of cases (one EGFR, two KRAS G12C). The tumours were clinically aggressive, exhibiting metastatic disease in most patients. Lung carcinomas with diffuse TTF1/p40 coexpression represent poorly differentiated NSCLCs with frequent basaloid features, but some show evidence of focal squamous, glandular or dual differentiation with a distinctly high rate of FGFR1 amplifications. The presence of targetable LUAD-type alterations (EGFR, KRAS G12C) emphasizes the importance of molecular testing in these tumours.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Thyroid Nuclear Factor 1 , Carcinoma, Non-Small-Cell Lung/genetics , Genomics , Lung Neoplasms/genetics , Carcinoma, Squamous Cell/genetics , DNA-Binding Proteins/genetics , Transcription Factors/genetics
3.
Genome Med ; 14(1): 127, 2022 11 15.
Article in English | MEDLINE | ID: mdl-36380343

ABSTRACT

BACKGROUND: Diffuse pleural mesothelioma (DPM) is an aggressive malignancy that, despite recent treatment advances, has unacceptably poor outcomes. Therapeutic research in DPM is inhibited by a paucity of preclinical models that faithfully recapitulate the human disease. METHODS: We established 22 patient-derived xenografts (PDX) from 22 patients with DPM and performed multi-omic analyses to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these PDX models and compared features to those of the matched primary patient tumors. Targeted next-generation sequencing (NGS; MSK-IMPACT), immunohistochemistry, and histologic subtyping were performed on all available samples. RNA sequencing was performed on all available PDX samples. Clinical outcomes and treatment history were annotated for all patients. Platinum-doublet progression-free survival (PFS) was determined from the start of chemotherapy until radiographic/clinical progression and grouped into < or ≥ 6 months. RESULTS: PDX models were established from both treatment naïve and previously treated samples and were noted to closely resemble the histology, genomic landscape, and proteomic profiles of the parent tumor. After establishing the validity of the models, transcriptomic analyses demonstrated overexpression in WNT/ß-catenin, hedgehog, and TGF-ß signaling and a consistent suppression of immune-related signaling in PDXs derived from patients with worse clinical outcomes. CONCLUSIONS: These data demonstrate that DPM PDX models closely resemble the genotype and phenotype of parental tumors, and identify pathways altered in DPM for future exploration in preclinical studies.


Subject(s)
Mesothelioma , Transcriptome , Animals , Humans , Xenograft Model Antitumor Assays , Heterografts , Proteomics , Mesothelioma/drug therapy , Mesothelioma/genetics , Genomics , Disease Models, Animal
4.
Nat Cancer ; 3(10): 1151-1164, 2022 10.
Article in English | MEDLINE | ID: mdl-36038778

ABSTRACT

Immunotherapy is used to treat almost all patients with advanced non-small cell lung cancer (NSCLC); however, identifying robust predictive biomarkers remains challenging. Here we show the predictive capacity of integrating medical imaging, histopathologic and genomic features to predict immunotherapy response using a cohort of 247 patients with advanced NSCLC with multimodal baseline data obtained during diagnostic clinical workup, including computed tomography scan images, digitized programmed death ligand-1 immunohistochemistry slides and known outcomes to immunotherapy. Using domain expert annotations, we developed a computational workflow to extract patient-level features and used a machine-learning approach to integrate multimodal features into a risk prediction model. Our multimodal model (area under the curve (AUC) = 0.80, 95% confidence interval (CI) 0.74-0.86) outperformed unimodal measures, including tumor mutational burden (AUC = 0.61, 95% CI 0.52-0.70) and programmed death ligand-1 immunohistochemistry score (AUC = 0.73, 95% CI 0.65-0.81). Our study therefore provides a quantitative rationale for using multimodal features to improve prediction of immunotherapy response in patients with NSCLC using expert-guided machine learning.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiology , Humans , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Programmed Cell Death 1 Receptor/therapeutic use , Genomics
5.
Clin Cancer Res ; 28(21): 4702-4713, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35792876

ABSTRACT

PURPOSE: RB1 mutations and loss of retinoblastoma (Rb) expression represent consistent but not entirely invariable hallmarks of small cell lung cancer (SCLC). The prevalence and characteristics of SCLC retaining wild-type Rb are not well-established. Furthermore, the performance of targeted next-generation sequencing (NGS) versus immunohistochemistry for Rb assessment is not well-defined. EXPERIMENTAL DESIGN: A total of 208 clinical SCLC samples were analyzed by comprehensive targeted NGS, covering all exons of RB1, and Rb IHC. On the basis of established coordination of Rb/p16/cyclinD1 expression, p16-high/cyclinD1-low profile was used as a marker of constitutive Rb deficiency. RESULTS: Fourteen of 208 (6%) SCLC expressed wild-type Rb, accompanied by a unique p16-low/cyclinD1-high profile supporting Rb proficiency. Rb-proficient SCLC was associated with neuroendocrine-low phenotype, combined SCLC with non-SCLC (NSCLC) histology and aggressive behavior. These tumors exclusively harbored CCND1 amplification (29%), and were markedly enriched in CDKN2A mutations (50%) and NSCLC-type alterations (KEAP1, STK11, FGFR1). The remaining 194 of 208 SCLC were Rb-deficient (p16-high/cyclinD1-low), including 184 cases with Rb loss (of which 29% lacked detectable RB1 alterations by clinical NGS pipeline), and 10 cases with mutated but expressed Rb. CONCLUSIONS: This is the largest study to date to concurrently analyze Rb by NGS and IHC in SCLC, identifying a 6% rate of Rb proficiency. Pathologic-genomic data implicate NSCLC-related progenitors as a putative source of Rb-proficient SCLC. Consistent upstream Rb inactivation via CDKN2A/p16↓ and CCND1/cyclinD1↑ suggests the potential utility of CDK4/6 inhibitors in this aggressive SCLC subset. The study also clarifies technical aspects of Rb status determination in clinical practice, highlighting the limitations of exon-only sequencing for RB1 interrogation. See related commentary by Mahadevan and Sholl, p. 4603.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Retinal Neoplasms , Retinoblastoma , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/pathology , Immunohistochemistry , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Genomics , Lung Neoplasms/pathology
6.
Mod Pathol ; 35(2): 193-201, 2022 02.
Article in English | MEDLINE | ID: mdl-34599282

ABSTRACT

Classic adenoid cystic carcinomas (C-AdCCs) of the breast are rare, relatively indolent forms of triple negative cancers, characterized by recurrent MYB or MYBL1 genetic alterations. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a rare variant of AdCC yet to be fully characterized. Here, we sought to determine the clinical behavior and repertoire of genetic alterations of SB-AdCCs. Clinicopathologic data were collected on a cohort of 104 breast AdCCs (75 C-AdCCs and 29 SB-AdCCs). MYB expression was assessed by immunohistochemistry and MYB-NFIB and MYBL1 gene rearrangements were investigated by fluorescent in-situ hybridization. AdCCs lacking MYB/MYBL1 rearrangements were subjected to RNA-sequencing. Targeted sequencing data were available for 9 cases. The invasive disease-free survival (IDFS) and overall survival (OS) were assessed in C-AdCC and SB-AdCC. SB-AdCCs have higher histologic grade, and more frequent nodal and distant metastases than C-AdCCs. MYB/MYBL1 rearrangements were significantly less frequent in SB-AdCC than C-AdCC (3/14, 21% vs 17/20, 85% P < 0.05), despite the frequent MYB expression (9/14, 64%). In SB-AdCCs lacking MYB rearrangements, CREBBP, KMT2C, and NOTCH1 alterations were observed in 2 of 4 cases. SB-AdCCs displayed a shorter IDFS than C-AdCCs (46.5 vs 151.8 months, respectively, P < 0.001), independent of stage. In summary, SB-AdCCs are a molecularly heterogeneous but clinically aggressive group of tumors. Less than 25% of SB-AdCCs display the genomic features of C-AdCC. Defining whether these tumors represent a single entity or a collection of different cancer types with a similar basaloid histologic appearance is warranted.


Subject(s)
Carcinoma, Adenoid Cystic , Carcinoma, Adenoid Cystic/genetics , Carcinoma, Adenoid Cystic/pathology , Genomics , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Oncogene Proteins, Fusion/genetics
7.
J Hematol Oncol ; 14(1): 170, 2021 10 16.
Article in English | MEDLINE | ID: mdl-34656143

ABSTRACT

BACKGROUND: Lineage plasticity, the ability to transdifferentiate among distinct phenotypic identities, facilitates therapeutic resistance in cancer. In lung adenocarcinomas (LUADs), this phenomenon includes small cell and squamous cell (LUSC) histologic transformation in the context of acquired resistance to targeted inhibition of driver mutations. LUAD-to-LUSC transdifferentiation, occurring in up to 9% of EGFR-mutant patients relapsed on osimertinib, is associated with notably poor prognosis. We hypothesized that multi-parameter profiling of the components of mixed histology (LUAD/LUSC) tumors could provide insight into factors licensing lineage plasticity between these histologies. METHODS: We performed genomic, epigenomics, transcriptomics and protein analyses of microdissected LUAD and LUSC components from mixed histology tumors, pre-/post-transformation tumors and reference non-transformed LUAD and LUSC samples. We validated our findings through genetic manipulation of preclinical models in vitro and in vivo and performed patient-derived xenograft (PDX) treatments to validate potential therapeutic targets in a LUAD PDX model acquiring LUSC features after osimertinib treatment. RESULTS: Our data suggest that LUSC transdifferentiation is primarily driven by transcriptional reprogramming rather than mutational events. We observed consistent relative upregulation of PI3K/AKT, MYC and PRC2 pathway genes. Concurrent activation of PI3K/AKT and MYC induced squamous features in EGFR-mutant LUAD preclinical models. Pharmacologic inhibition of EZH1/2 in combination with osimertinib prevented relapse with squamous-features in an EGFR-mutant patient-derived xenograft model, and inhibition of EZH1/2 or PI3K/AKT signaling re-sensitized resistant squamous-like tumors to osimertinib. CONCLUSIONS: Our findings provide the first comprehensive molecular characterization of LUSC transdifferentiation, suggesting putative drivers and potential therapeutic targets to constrain or prevent lineage plasticity.


Subject(s)
Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Animals , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Transdifferentiation , Humans , Mice, Inbred NOD , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-myc/genetics , Signal Transduction , Transcriptome
8.
Eng. sanit. ambient ; 26(2): 369-379, Mar.-Apr. 2021. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1249758

ABSTRACT

RESUMO O Plano de Segurança da Água (PSA) contempla, entre outras etapas, a identificação e o acompanhamento de eventos perigosos e pode garantir qualidade hídrica aos consumidores. A ruralidade abrange cerca de 15% da população brasileira e o acompanhamento técnico é insuficiente para atender às demandas locais. Nesse contexto, o principal objetivo foi elaborar um modelo conceitual de PSA para monitoramento de riscos à contaminação da água na área rural, contemplando eventos desde a captação até a distribuição de água em comunidades rurais. A metodologia consistiu em caracterização de eventos perigosos, concepção do modelo computacional, consulta a especialistas e calibração e aplicação do modelo em propriedades rurais. Entre os resultados, tem-se um software elaborado em Python contendo 109 eventos direcionados ao abastecimento rural. O programa analisou a precariedade no entorno da captação de água e as condições de limpeza das propriedades estudadas. Os resultados indicaram que os riscos mais elevados, em sua maioria, são provenientes do uso de fossa negra, descarte irregular de resíduos sólidos, lançamento de esgoto doméstico a céu aberto e criação de animais nas proximidades da captação de água. Não há softwares disponíveis para mensuração de riscos ao abastecimento de água em áreas rurais e o modelo proposto pode ser utilizado para avaliação da salubridade rural no contexto nacional. Dessa forma, o software subsidia o monitoramento dos recursos hídricos e amplia a capacidade de gerenciamento no setor.


ABSTRACT The Water Safety Plan (WSP) includes, among other steps, the identification and monitoring of dangerous events can guarantee water quality to consumers. Rurality covers about 15% of the Brazilian population and technical support is insufficient to assist local demands. In this context, the main objective was to develop a conceptual WSP model for monitoring water contamination risks in the rural area, contemplating events from water catchment to water distribution in rural communities. The methodology consisted of the characterization of dangerous events, conception of the computational model, specialists consultation, and model calibration and application in rural properties. Among the results, there is a software elaborated in Python containing 109 events aimed at rural supply. The program analyzed the precariousness around the water catchment and the clean conditions of the studied properties. These results indicated the highest risks, for the most part, come from the use of cesspool, irregular disposal of solid waste, domestic sewage discharge, and animal beeding nearby water catchment. There is no software available to measure water supply risks in rural areas and the proposed model can be used for environmental health evaluatiation in the national context. In this way, the software can support water resource monitoring and expands the manageability in the sector.

9.
Mod Pathol ; 33(11): 2221-2232, 2020 11.
Article in English | MEDLINE | ID: mdl-32612248

ABSTRACT

The Ventana PD-L1 SP142 immunohistochemistry (IHC) assay is the FDA-approved companion diagnostic assay for atezolizumab therapy selection for patients with PD-L1-positive locally advanced or metastatic triple-negative breast carcinoma (TNBC). We aimed to elucidate clinical, pathologic, and molecular features associated with PD-L1 expression in TNBCs. Clinical, pathologic, and next-generation sequencing (NGS)-based molecular data for TNBCs tested with PD-L1 (SP142) IHC at our institution between 11/2018 and 12/2019 were retrieved and reviewed. PD-L1 positivity was defined as ≥1% IC staining. Patients with metastatic TNBC treated at first line with atezolizumab regimens were evaluated for treatment response and for time to treatment failure (TTF). Among 156 TNBCs, PD-L1 was positive in 47.4% of cases. Primary TNBCs were significantly more frequently PD-L1 positive, compared with recurrent/metastatic samples (p = 0.002). PD-L1-positive TNBCs had increased stromal IC, compared with PD-L1-negative samples (p < 0.001). The repertoire of somatic genetic alterations of PD-L1-positive and PD-L1-negative TNBCs was similar. Matched primary and recurrent/metastatic TNBC samples were available for eight patients, in whom four had discordant results. Thirty patients with metastatic TNBC were treated with atezolizumab regimens, with treatment failure occurring in 16 patients and a median TTF of 5.1 months in this early evaluation. The findings of this study show stromal ICs in primary TNBCs are more likely to show PD-L1 positivity than in recurrent or metastatic samples. This information should guide selection of samples suitable for testing. Further studies are needed to identify other features associated with PD-L1-positive breast carcinomas and clinical benefit of treatment.


Subject(s)
B7-H1 Antigen/metabolism , Lymphocytes, Tumor-Infiltrating/metabolism , Stromal Cells/metabolism , Triple Negative Breast Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Stromal Cells/immunology , Stromal Cells/pathology , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/pathology , Young Adult
10.
Arch Pathol Lab Med ; 144(5): 597-601, 2020 05.
Article in English | MEDLINE | ID: mdl-31647316

ABSTRACT

CONTEXT.­: The American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline in breast cancer was updated in 2018 to address issues on interpretation of uncommon results using dual-probe in situ hybridization according to the 2013 guideline. OBJECTIVE.­: To assess impact of the 2018 guideline on breast cancer with equivocal HER2 immunohistochemistry results. DESIGN.­: We retrospectively reviewed HER2 fluorescence in situ hybridization (FISH) data (HER2/CEP17 ratio and average HER2 copy number per cell) of HER2 immunohistochemistry-equivocal (2+ or 1+ to 2+) breast cancers at our center between January 2014 and May 2018 and compared HER2 FISH results according to 2013 and 2018 guidelines. RESULTS.­: A total of 1666 HER2 FISH results from 1421 patients with equivocal HER2 immunohistochemistry were reviewed. Based on the 2013 guideline, HER2 FISH results were amplified in 346 cases (20.8%), equivocal in 242 (14.5%), and nonamplified in 1078 (64.7%). Using the 2018 guideline, 258 cases (16%) were reclassified, including 242 previously equivocal test results (15%) and 16 previously positive results (1%) reclassified as negative. The subset of 2013 HER2-equivocal and 2018 HER2-nonamplified cases with HER2/CEP17 ratio lower than 2.0 and average HER2 copy number 4.0 or higher and lower than 6.0 showed higher incidence of micropapillary morphology compared with HER2-amplified cases. Despite most patients in this group not receiving HER2-targeted treatment, 96% had no evidence of disease at follow-up. CONCLUSIONS.­: The 2018 guideline eliminated HER2 FISH-equivocal cases by reclassifying HER2-equivocal cases and cases with nonclassical amplification without HER2 overexpression as HER2 negative. As a consequence, we observed a considerable increase in HER2 FISH-negative cases and a slight decrease in HER2 FISH-positive cases.


Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , DNA Copy Number Variations , Receptor, ErbB-2/genetics , Adult , Aged , Aged, 80 and over , American Medical Association , Biomarkers, Tumor/metabolism , Breast Neoplasms/classification , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Centromere/genetics , Chromosomes, Human, Pair 17/genetics , Cohort Studies , Female , Guidelines as Topic , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Medical Oncology , Middle Aged , Pathologists , Receptor, ErbB-2/metabolism , Retrospective Studies , United States
11.
Breast J ; 25(5): 829-837, 2019 09.
Article in English | MEDLINE | ID: mdl-31197914

ABSTRACT

The 8th edition of the American Joint Committee on Cancer (AJCC) staging guidelines combine traditional TNM system with biomarkers to reflect our current understanding of tumor biology and targeted therapy. In this study, we investigated the impact of the TNM + Biomarkers staging system and the additive value of Oncotype Dx™ genomic profile recurrence score (RS) (TNM + Biomarkers+RS <11) for the staging of breast cancer (BC) using data from two tertiary referral cancer centers. Compared to TNM alone, the TNM + Biomarkers system changed the stage group in 32.7% of BCs (27% downstage, 5.7% upstage). Most (98.3%) of the downstaged BCs were estrogen receptor (ER)+/progesterone receptor (PR)+, whereas 78% of the upstaged BCs were ER-/PR-/human epidermal growth factor receptor 2 (HER2)-. Compared to TNM + Biomarkers staging, the addition of genetic profile data (TNM + Biomarker+RS <11) downstaged only <1% BCs. Our analysis suggests that for T1-T2N0 ER+/HER2- BCs, Oncotype Dx™ RS <11 provides added value as a staging parameter only in a very small group of cases compared to TNM + Biomarkers alone.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Neoplasm Staging/methods , Practice Guidelines as Topic , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Carcinoma, Ductal, Breast/genetics , Carcinoma, Lobular/genetics , Female , Genetic Profile , Humans , Middle Aged , Neoplasm Grading
12.
Breast Cancer Res Treat ; 177(1): 61-66, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31144151

ABSTRACT

PURPOSE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are known to have significant clinical and pathological response to neoadjuvant systemic therapy (NST). The aim of this study was to identify factors associated with pathological complete response (pCR), defined as no residual invasive carcinoma in the breast and axillary lymph nodes (ypT0/is ypN0), among patients with HER2-positive breast cancer and to compare pCR rates between breast cancers with HER2 protein overexpression by immunohistochemistry (IHC) versus HER2 gene amplification by fluorescence in situ hybridization (FISH) in the absence of protein overexpression by IHC. METHODS: We conducted a retrospective review of HER2-positive breast cancer patients treated with NST and surgery at Memorial Sloan Kettering Cancer Center between January 2013 and May 2018. Estrogen receptor (ER), progesterone receptor (PR), and HER2 status were assessed according to the 2018 ASCO/CAP guidelines. RESULTS: During the study period, 560 patients were identified. Of 531 patients with IHC results available, 455 patients had HER2 IHC 3+, and 76 had IHC < 3+ but HER2 amplification detected by FISH. The overall pCR rate was 59% (330/560). The pCR rate among patients with HER2 protein overexpression (IHC 3+) was 67%, compared to 17% among patients with HER2 amplification by FISH (IHC < 3+). On univariate and multivariate analyses, HER2 protein overexpression by IHC (IHC 3+) was a significant predictor of pCR, along with grade 3 histology, PR-negative status, and dual anti-HER2 therapy. CONCLUSION: Although both HER2 IHC and FISH are standard HER2 testing methods in breast cancer, achievement of pCR is associated with HER2 IHC expression level, among other factors.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Receptor, ErbB-2/genetics , Adult , Biopsy, Large-Core Needle , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Combined Modality Therapy , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Retrospective Studies , Treatment Outcome
13.
Eng. sanit. ambient ; 24(1): 109-119, jan.-fev. 2019. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1001937

ABSTRACT

RESUMO O Plano de Segurança da Água representa a estratégia de previsão de perigos e monitoramento de riscos que podem ameaçar a qualidade da água para consumo humano. O trabalho teve o intuito de estudar o Plano de Segurança da Água implantado na estação de tratamento de água Guaraú, de modo a identificar sua concepção metodológica, seus desafios e suas potencialidades para o controle efetivo do sistema de abastecimento de água. Os documentos que subsidiaram a elaboração do plano foram as recomendações da Organização Mundial da Saúde e as exigências do padrão de potabilidade, previstos pela Portaria nº 2.914/2011, do Ministério da Saúde. Para tratamento de água, a companhia gestora do saneamento na Região Metropolitana de São Paulo adotou a metodologia de Beuken et al. (2008) e a proposta de Brasil (2012) para caracterização do perigo e avaliação de riscos. A avaliação indica que quanto maior o valor atribuído a determinado parâmetro, maior é a atenção necessária a este ao longo do sistema de abastecimento de água. A empresa instituiu o Plano de Segurança da Água para otimizar os processos de tratamento e garantir qualidade na distribuição de água potável de forma eficiente. Essa empresa iniciou discussões internas sobre o instrumento em 2006, identificou uma metodologia que pudesse expressar as diretrizes da política ambiental, elaborou o modelo do Plano de Segurança da Água, realizou reuniões técnicas e implantou o plano na estação de tratamento do Guaraú. Os principais resultados foram a sistematização de registros, a implementação de novos procedimentos, a aquisição de equipamentos, a capacitação técnica e a identificação de pontos de controle. O maior desafio foi implantar um instrumento preventivo viável e dinâmico para gestão hídrica. Ressalta-se que o sucesso do plano depende, entre outros fatores, de dados atualizados, da participação da alta administração e dos ajustes necessários requeridos pela própria metodologia. Há falta de estudos científicos e manuais práticos sobre o tema.


ABSTRACT Water Safety Plans represent the strategy for predicting hazards and monitoring risks that can threat the water quality for human consumption. This paper intended to study Water Safety Plans implemented at Guaraú water treatment plant in order to identify its methodological requirements, challenges and opportunities for the effective control in water supply systems. The documents that supported the plan were the World Health Organization recommendations and the drinking water standards of Brazilian regulation 2914/2010 by Health Ministry. Regarding water treatment, the managers of sanitation in the metropolitan areaof São Paulo adopted Beuken et al. (2008) and Brazil (2012) methodologies for hazard description and risk evaluation. This evaluation model proposes that the greater value associated to a certain parameter meansit needs more attentionthan another in the water supply system. The company has implemented Water Safety Plans to optimize its treatment processes and to ensure water distribution with quality and efficiency. The company has been discussing about this tool since 2006; it identified a methodology that could express the environmental policy guidelines, elaborated a model of Water Safety Plans, held technical meetings and applied the plan to Guaraú water treatment plant. The main results were records systematization, implementation of new procedures, acquisition of equipment, technical capacitation and identification of control points. The greatest challenge was to establish a feasible and dynamic preventive tool for managing water resources. It must be emphasized that the Water Safety Plans success depends on, among other variables, an up-to-date database, the cooperation of decision-makers and continuous adjustments required by the methodology itself. There is not sufficient scientific studies and handbooks about this subject.

14.
Brasília; IPEA; 2012. 57 p. ilus, graf.
Monography in Portuguese | ECOS, LILACS | ID: biblio-991834

ABSTRACT

O relatório tem apresenta o panorama dos resíduos de serviços de saúde (RSS) no país, como subsídio à elaboração do Plano Nacional de Resíduos Sólidos (PNRS). Visa reunir e analisar o máximo possível de dados e informações relativos aos RSS, obtidos no período de três meses para a preparação do presente diagnóstico. Mapear as condições do gerenciamento de RSS nas esferas públicas. Identificar o arcabouço legal pertinente ao tema e estruturar diretrizes de apoio, em caráter preliminar, para a elaboração do PNRS.


Subject(s)
Data Collection , Legislation , Solid Waste , Health Services
15.
Eng. sanit. ambient ; 15(2): 167-176, jun. 2010. ilus, tab
Article in Portuguese | LILACS | ID: lil-561321

ABSTRACT

O presente trabalho propôs um modelo de avaliação do gerenciamento de RSS em estabelecimentos de saúde, com o uso de indicadores de desempenho. A proposta consistiu em identificar esses indicadores a partir dos dados qualitativos obtidos por entrevistas, cujas respostas foram associadas a escalas numéricas e inseridas no programa Statistica (StatSoft®) para efetuar a análise fatorial (AF). Para isso, foi elaborado um roteiro de entrevista, especialmente preparado com 29 variáveis de observação e aplicado a 98 profissionais da saúde da Santa Casa de Misericórdia de São Carlos (SP). Os indicadores de desempenho foram submetidos ao julgamento de especialistas para a sua classificação em ordem de importância, com o uso da matriz de avaliação do método AHP (Analytic Hierarchy Process). Por fim, foi composto um índice global, que possibilitou a avaliação geral da situação investigada, em uma escala de zero a um, indicando que ações de melhoria para esse gerenciamento devem ser desenvolvidas. Este trabalho foi desenvolvido a fim de estruturar um modelo de avaliação de desempenho por meio da identificação de indicadores qualitativos, auxiliando na eficiência do processo de gerenciamento de resíduos em ambientes de saúde.


This paper proposed a model of evaluation of healthcare waste (HW) management in health establishments by the use of performance indicators. It was structured to identify these indicators by qualitative data obtained from interviews. The answers were associated to a numerical scale and were inserted in Statistica program (StatSoft®) to calculate the factor analysis (FA). A script of interview containing 29 observation variables was especially prepared and applied to 98 health professionals of Santa Casa de Misericórdia de São Carlos, São Carlos (SP), Brazil. Performance indicators were evaluated by experts who ordered them in terms of importance using Analytic Hierarchy Process (AHP) method. Finally, it was composed a global index that allowed the general evaluation of the analyzed situation, in a scale from zero to one, pointing to the actions of improvement to this management. This paper was developed in order to elaborate a model of performance evaluation by the identification of qualitative indicators, promoting an efficient waste management process in health environment.

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