RESUMEN
Malignant papillary lesions, and in particular, encapsulated papillary carcinoma (EPC) of the breast, continue to present diagnostic challenges for the practising pathologist. In addition to the relative rarity of these lesions, the lack of evidence-based diagnostic criteria, differences in the biological characteristics, and the clinical behaviour of in situ and invasive forms, variable use of immunohistochemical markers, and overlap with other tumour types including high-grade circumscribed forms of invasive breast carcinomas has resulted in diagnostic discordance with potentially significant clinical and management implications. Pathologists should be familiar with the range of morphology observed in malignant papillary tumours, EPC, and EPC-like tumours and the existence of tumours with overlapping features. In this review we summarize the common diagnostic pitfalls in malignant papillary tumours and provide an approach to the diagnostic evaluation and categorisation of these enigmatic entities.
RESUMEN
Tumour protein 63 (p63) is a transcription factor of the p53 gene family, encoded by the TP63 gene located at chromosome 3q28, which regulates the activity of genes involved in growth and development of the ectoderm and derived tissues. p63 protein is normally expressed in the nuclei of the basal cell layer of glandular organs, including breast, in squamous epithelium and in urothelium. p63 immunohistochemical (IHC) staining has several applications in diagnostic breast pathology. It is commonly used to demonstrate myoepithelial cells at the epithelial stromal interface to differentiate benign and in situ lesions from invasive carcinoma and to characterize and classify papillary lesions including the distinction of breast intraduct papilloma from skin hidradenoma. p63 IHC is also used to identify and profile lesions showing myoepithelial cell and/or squamous differentiation, e.g. adenomyoepithelioma, salivary gland-like tumours including adenoid cystic carcinoma, and metaplastic breast carcinoma including low-grade adenosquamous carcinoma. This article reviews the applications of p63 IHC in diagnostic breast pathology and outlines a practical approach to the diagnosis and characterization of breast lesions through the identification of normal and abnormal p63 protein expression. The biology of p63, the range of available antibodies with emphasis on staining specificity and sensitivity, and pitfalls in interpretation are also discussed. The TP63 gene in humans, which shows a specific genomic structure, resulting in either TAp63 (p63) isoform or ΔNp63 (p40) isoform. As illustrated in the figure, both isoforms contain a DNA-binding domain (Orange box) and an oligomerization domain (Grey box). TAp63 contains an N-terminal transactivation (TA) domain (Green box), while ΔNp63 has an alternative terminus (Yellow box). Antibodies against conventional pan-p63 (TP63) bind to the DNA binding domain common to both isoforms (TAp63 and p40) and does not distinguish between them. Antibodies against TAp63 bind to the N-terminal TA domain, while antibodies specific to ΔNp63 (p40) bind to the alternative terminus. Each isoform has variant isotypes (α, ß, γ, δ, and ε).
Asunto(s)
Neoplasias de la Mama , Mama , Proteínas Supresoras de Tumor , Femenino , Humanos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , ADN , Inmunohistoquímica , Isoformas de Proteínas/genética , Animales , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Mama/metabolismo , Mama/patologíaRESUMEN
AIMS: In this study, we validate the use of Nottingham Prognostic x (NPx), consisting of tumour size, tumour grade, progesterone receptor (PR) and Ki67 in luminal BC. MATERIALS AND METHODS: Two large cohorts of luminal early-stage BC (n = 2864) were included. PR and Ki67 expression were assessed using full-face resection samples using immunohistochemistry. NPx was calculated and correlated with clinical variables and outcome, together with Oncotype DX recurrence score (RS), that is frequently used as a risk stratifier in luminal BC. RESULTS: In the whole cohort, 38% of patients were classified as high risk using NPx which showed significant association with parameters characteristics of aggressive tumour behaviour and shorter survival (P < 0.0001). NPx classified the moderate Nottingham Prognostic Index (NPI) risk group (n = 1812) into two distinct prognostic subgroups. Of the 82% low-risk group, only 3.8% developed events. Contrasting this, 14% of the high-risk patients developed events during follow-up. A strong association was observed between NPx and Oncotype Dx RS (P < 0.0001), where 66% of patients with intermediate risk RS who had subsequent distant metastases also had a high-risk NPx. CONCLUSION: NPx is a reliable prognostic index in patients with luminal early-stage BC, and in selected patients may be used to guide adjuvant chemotherapy recommendations.
Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Anciano , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Medición de Riesgo , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Anciano de 80 o más AñosRESUMEN
BACKGROUND AND OBJECTIVES: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organizations. METHODS AND RESULTS: The established ICCR process for dataset development was followed. An international expert panel consisting of breast pathologists, a surgeon, and an oncologist prepared a draft set of core and noncore data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalized and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS: This first international dataset for invasive cancer of the breast is intended to promote high-quality, standardized pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve the management of invasive breast cancer patients.
Asunto(s)
Neoplasias de la Mama , Humanos , Neoplasias de la Mama/patología , Femenino , Patología Clínica/normas , Conjuntos de Datos como Asunto/normasRESUMEN
AIMS: The International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations, is an initiative aimed at providing a unified international approach to reporting cancer. ICCR recently published new data sets for the reporting of invasive breast carcinoma, surgically removed lymph nodes for breast tumours and ductal carcinoma in situ, variants of lobular carcinoma in situ and low-grade lesions. The data set in this paper addresses the neoadjuvant setting. The aim is to promote high-quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment that can be used for subsequent management decisions for each patient. METHODS: The ICCR convened expert panels of breast pathologists with a representative surgeon and oncologist to critically review and discuss current evidence. Feedback from the international public consultation was critical in the development of this data set. RESULTS: The expert panel concluded that a dedicated data set was required for reporting of breast specimens post-neoadjuvant therapy with inclusion of data elements specific to the neoadjuvant setting as core or non-core elements. This data set proposes a practical approach for handling and reporting breast resection specimens following neoadjuvant therapy. The comments for each data element clarify terminology, discuss available evidence and highlight areas with limited evidence that need further study. This data set overlaps with, and should be used in conjunction with, the data sets for the reporting of invasive breast carcinoma and surgically removed lymph nodes from patients with breast tumours, as appropriate. Key issues specific to the neoadjuvant setting are included in this paper. The entire data set is freely available on the ICCR website. CONCLUSIONS: High-quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment are critical for subsequent management decisions for each patient.
Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Conjuntos de Datos como AsuntoRESUMEN
PURPOSE: Ductal carcinoma in situ (DCIS) associated with invasive carcinoma ≤ 1 mm in size is defined as DCIS with microinvasion (DCIS/microinvasion) rather than as invasive breast carcinoma. The number of patients with microinvasion accounts for < 1% of all breast cancer in published studies. As the numbers are limited, the prognostic significance of DCIS/microinvasion has not been clearly elucidated. This meta-analysis aimed to investigate the survival differences between patients with DCIS/microinvasion and those with pure DCIS. METHODS: A meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was performed. We searched three electronic databases (MEDLINE, Cochrane Library, and EMBASE) and included observational studies published in English that contained survival details of patients with either DCIS or DCIS/microinvasion. RESULTS: This study identified 26 studies that described the clinicopathological characteristics of patients in both the DCIS and DCIS/microinvasion groups. Survival differences were evaluated in 10 of 26 studies. Disease-free survival and loco-regional recurrence-free survival were significantly shorter in patients with DCIS/microinvasion than in those with DCIS (Hazard ratio, 1.52; 95% confidence interval, 1.11-2.08; p = 0.01 and hazard ratio, 2.53; 95% confidence interval, 1.45-4.41; p = 0.001, respectively). Both overall survival and distant metastasis-free survival tended to be shorter in patients with DCIS/microinvasion than in patients with DCIS (Hazard ratio, 1.63; 95% CI, 0.63-4.23; p = 0.31 and hazard ratio, 1.85; 95% confidence interval, 0.74-4.66; p = 0.19, respectively) but the difference was not statistically significant. CONCLUSION: Our meta-analysis suggests that DCIS/microinvasion may display more aggressive biological and clinical behavior than pure DCIS, highlighting the potential need for closer follow-up and consideration of adjuvant treatment strategies in DCIS patients with microinvasive disease.
Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/patología , Neoplasias de la Mama/patología , Pronóstico , Mama/patología , Supervivencia sin Enfermedad , Carcinoma Ductal de Mama/patología , Invasividad Neoplásica/patología , Estudios RetrospectivosRESUMEN
Accurate pathological diagnosis is the cornerstone of optimal clinical management for patients with breast disease. As non-operative diagnosis has now become the standard of care, histopathologists encounter the daily challenge of making definitive diagnoses on limited breast core needle biopsy (CNB) material. CNB samples are carefully evaluated using microscopic examination of haematoxylin and eosin (H&E)-stained slides and supportive immunohistochemistry (IHC), providing the necessary information to inform the next steps in the patient care pathway. Some entities may be difficult to distinguish on small tissue samples, and if there is uncertainty a diagnostic excision biopsy should be recommended. This review discusses (1) benign breast lesions that may mimic malignancy, (2) malignant conditions that may be misinterpreted as benign, (3) malignant conditions that may be incorrectly diagnosed as primary breast carcinoma, and (4) some IHC pitfalls. The aim of the review is to raise awareness of potential pitfalls in the interpretation of breast lesions that may lead to underdiagnosis, overdiagnosis, or incorrect classification of malignancy with potential adverse outcomes for individual patients.
Asunto(s)
Microscopía , HumanosRESUMEN
Breast cancer (BC) is a heterogeneous disease, encompassing a diverse spectrum of tumours with varying morphological, biological, and clinical phenotypes. Although tumours may show phenotypic overlap, they often display different biological behaviour and response to therapy. Advances in high-throughput molecular techniques and bioinformatics have contributed to improved understanding of BC biology and refinement of molecular taxonomy with the identification of specific molecular subclasses. Although the traditional pathological morphological classification of BC is of paramount importance and provides diagnostic and prognostic information, current interest focusses on the use of a single gene and multigene assays to stratify BC into distinct groups to guide decisions on systemic therapy. This review considers approaches to the classification of BC, including their limitations, and with particular emphasis on the fundamental role of morphology in establishing an accurate diagnosis of primary invasive carcinoma of breast origin. This forms the basis for further morphological characterization and for all other approaches to BC classification that are used to provide prognostic and therapeutic predictive information.
Asunto(s)
Biología Computacional , Neoplasias , HumanosRESUMEN
BACKGROUND: OncoMasTR is a recently developed multigene prognostic test for early-stage breast cancer. The test has been developed in a kit-based format for decentralized deployment in molecular pathology laboratories. The analytical performance characteristics of the OncoMasTR test are described in this study. METHODS: Expression levels of 6 genes were measured by 1-step reverse transcription-quantitative PCR on RNA samples prepared from formalin-fixed, paraffin-embedded (FFPE) breast tumor specimens. Assay precision, reproducibility, input range, and interference were determined using FFPE-derived RNA samples representative of low and high prognostic risk scores. A pooled RNA sample derived from 6 FFPE breast tumor specimens was used to establish the linear range, limit of detection, and amplification efficiency of the individual gene expression assays. RESULTS: The overall precision of the OncoMasTR test was high with an SD of 0.16, which represents less than 2% of the 10-unit risk score range. Test results were reproducible across 4 testing sites, with correlation coefficients of 0.94 to 0.96 for the continuous risk score and concordance of 86% to 96% in low-/high-risk sample classification. Consistent risk scores were obtained across a > 100-fold RNA input range. Individual gene expression assays were linear up to quantification cycle values of 36.0 to 36.9, with amplification efficiencies of 80% to 102%. Test results were not influenced by agents used during RNA isolation, by low levels of copurified genomic DNA, or by moderate levels of copurified adjacent nontumor tissue. CONCLUSION: The OncoMasTR prognostic test displays robust analytical performance that is suitable for deployment by local pathology laboratories for decentralized use.
Asunto(s)
Neoplasias de la Mama , Biomarcadores de Tumor/genética , Mama/patología , Neoplasias de la Mama/patología , Femenino , Formaldehído , Perfilación de la Expresión Génica/métodos , Humanos , Adhesión en Parafina , Pronóstico , ARN/análisis , Receptores de Estrógenos/metabolismo , Reproducibilidad de los ResultadosRESUMEN
AIMS: Although evaluation of nuclear morphology is important for the diagnosis and categorisation of breast lesions, the criteria used to assess nuclear atypia rely upon the subjective evaluation of several features that may result in inter- and intraobserver variation. This study aims to refine the definitions of cytonuclear features in various breast lesions. METHODS AND RESULTS: ImageJ was used to assess the nuclear morphological features including nuclear diameter, axis length, perimeter, area, circularity and roundness in 160 breast lesions comprising ductal carcinoma in situ (DCIS), invasive breast carcinoma of no special type (IBC-NST), tubular carcinoma, usual ductal hyperplasia (UDH), columnar cell change (CCC) and flat epithelial atypia (FEA). Reference cells included normal epithelial cells, red blood cells (RBCs) and lymphocytes. Reference cells showed size differences not only between normal epithelial cells and RBCs but also between RBCs in varied-sized blood vessels. Nottingham grade nuclear pleomorphism scores 1 and 3 cut-offs in IBC-NST, compared to normal epithelial cells, were < ×1.2 and > ×1.4 that of mean maximum Feret's diameter and < ×1.6 and > ×2.4 that of mean nuclear area, respectively. Nuclear morphometrics were significantly different in low-grade IBC-NST versus tubular carcinoma, low-grade DCIS versus UDH and CCC versus FEA. No differences in the nuclear features between grade-matched DCIS and IBC-NST were identified. CONCLUSION: This study provides a guide for the assessment of nuclear atypia in breast lesions, refines the comparison with reference cells and highlights the potential diagnostic value of image analysis tools in the era of digital pathology.
Asunto(s)
Adenocarcinoma , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Núcleo Celular/patología , Variaciones Dependientes del Observador , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Biopsia , Neoplasias de la Mama/patología , Neoplasias de la Mama/ultraestructura , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/ultraestructura , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/ultraestructura , Células Epiteliales/patología , Células Epiteliales/ultraestructura , Femenino , Humanos , Hiperplasia/patologíaRESUMEN
BACKGROUND AND AIMS: Chromosome 17 alterations affect the assessment of HER2 gene amplification in breast cancer (BC), but its clinical significance remains unclear. This study aimed to identify the prevalence of centromere enumeration probe 17 (CEP17) alterations, and its correlation with response to neoadjuvant therapy (NAT) in BC patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry-equivocal score. METHODS AND RESULTS: A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in-situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2-amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5-< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2-non-amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2-amplified and HER2-non-amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2-amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37-102.00; P = 0.02], and histological grade 3 in HER2 non-amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61-19.00; P = 0.007). CONCLUSION: The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry-equivocal score who would benefit from NAT.
Asunto(s)
Neoplasias de la Mama , Aberraciones Cromosómicas , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Centrómero , Cromosomas Humanos Par 17/genética , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ/métodos , Receptor ErbB-2/análisisRESUMEN
The management of patients with breast cancer (BC) relies on the assessment of a defined set of well-established prognostic and predictive markers. Despite overlap, prognostic markers are used to assess the risk of recurrence and the likely benefit of systemic therapy, whereas predictive markers are used to determine the type of systemic therapy to be offered to an individual patient. In this review, we provide an update and present some challenges in the assessment of the main BC-specific molecular predictive markers, namely hormone receptors (oestrogen receptor [ER] and progesterone receptor [PR]), human epidermal growth factor receptor 2 (HER2), and KI67. As the main platform for assessing these markers in BC is immunohistochemistry (IHC), we address the cut-off values used to define positivity, the ER-low subgroup, the existence and significance of the ER-/PR+ phenotype, the use of PR in routine practice, and the role of hormone receptors in ductal carcinoma in situ. We discuss the newly introduced HER2-low class of BC and the clinical/biological difference between different HER2 groups (e.g., HER2 IHC score 3+ BCs vs. those with a HER2 IHC score 2+ with HER2 gene amplification). The review concludes with an update on the applications of KI67 assessment in BC and observations on the role of immune checkpoint identification in BC.
Asunto(s)
Neoplasias de la Mama , Receptores de Progesterona , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Hormonas , Humanos , Antígeno Ki-67/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismoRESUMEN
BACKGROUND: Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question "Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?" METHODS: The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS). RESULTS: Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests. CONCLUSIONS: The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Quimioterapia Adyuvante/métodos , Recurrencia Local de Neoplasia/genética , Guías de Práctica Clínica como Asunto/normas , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Europa (Continente) , Femenino , Perfilación de la Expresión Génica , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
BACKGROUND: The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT). METHODS: 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed. RESULTS: 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017). CONCLUSION: No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.
Asunto(s)
Neoplasias de la Mama , Dosificación de Gen , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Terapia Neoadyuvante , Clasificación del Tumor , Receptor ErbB-2/análisis , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios RetrospectivosRESUMEN
The response of human epidermal growth factor receptor2 (HER2)- positive breast cancer (BC) patients to anti-HER2 targeted therapy is significant. However, the response is not uniform and a proportion of HER2-positive patients do not respond. This study aims to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive BC patients. The study group comprised 500 BC patients treated with neoadjuvant chemotherapy (NACT) and/or neoadjuvant anti-HER2 therapy and surgery who had tumours that were 3+ or 2+ with HER2 immunohistochemistry (IHC). HER2 IHC 2+ tumours were classified into five groups by fluorescence in situ hybridisation (FISH) according to the 2018 ASCO/CAP guidelines of which Groups 1, 2 and 3 were considered HER2 amplified. Pathological complete response (pCR) was more frequent in HER2 IHC 3+ tumours than in HER2 IHC 2+/HER2 amplified tumours, when either in receipt of NACT alone (38% versus 13%; p = 0.22) or neoadjuvant anti-HER2 therapy (52% versus 20%; p < 0.001). Multivariate logistic regression analysis showed that HER2 IHC 3+ and histological grade 3 were independent predictors of pCR following neoadjuvant anti-HER2 therapy. In the HER2 IHC 2+/HER2 amplified tumours or ASCO/CAP FISH Group 1 alone, ER-negativity was an independent predictor of pCR following NACT and/or neoadjuvant anti-HER2 therapy. In the current study, 22% of HER2-positive tumours became HER2-negative by IHC and FISH following neoadjuvant treatment, the majority (74%) HER2 IHC 2+/HER2 amplified tumours. Repeat HER2 testing after neoadjuvant treatment should therefore be considered.
Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Receptor ErbB-2/análisis , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Quimioterapia Adyuvante/métodos , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Resultado del TratamientoRESUMEN
Breast lesions with a prominent myoepithelial cell component constitute a heterogeneous group of benign and malignant neoplastic proliferations. These lesions are often dual epithelial-myoepithelial, but may be purely myoepithelial cell in nature. Benign epithelial-myoepithelial lesions typically maintain the morphology and immunophenotype of the normal bilayer epithelial myoepithelial structures. However, the distinction between the two cell components is not always clear-cut in malignant lesions in which the histogenesis of myoepithelial cells remains uncertain. Neoplastic biphasic epithelial-myoepithelial lesions of the breast include adenomyoepithelioma (AME), pleomorphic adenoma and adenoid cystic carcinoma. Four histological patterns of classical AME have been described: tubular, lobulated, spindle-cell and adenosis variants. Overlapping patterns occur and some AMEs display an intraductal papillary pattern that may represent a fifth variant. AME can be benign or malignant. Classical AME may show atypical features, which are not sufficient for the diagnosis of malignancy (atypical AME). Atypical AME is recognised as a lesion of uncertain malignant potential with limited metastatic capability. Based on the histological features, we propose a classification of malignant AME (M-AME) into three variants: M-AME in situ, M-AME invasive and AME with invasive carcinoma. In this review, we provide an overview of myoepithelial lesions of the breast focusing on the classification of AME to improve not only the consistency of reporting but also help to guide further management decision-making.
Asunto(s)
Adenomioepitelioma/clasificación , Neoplasias de la Mama/clasificación , Adenomioepitelioma/patología , Neoplasias de la Mama/patología , Femenino , HumanosRESUMEN
AIMS: Although rare, malignant sarcomatoid breast tumours without evidence of epithelial differentiation comprise a diagnostic challenge with management implications. Earlier studies have generally considered these to be primary breast sarcomas; however, supporting evidence is lacking and management remains variable. This study aimed to provide an evidence-based approach to improve the consistency of diagnosis and management for such cases. METHODS AND RESULTS: A large series (n = 140) of metaplastic breast carcinoma (MBC) diagnosed in Nottingham over 18 years was analysed. Only cases with available data on immunohistochemical expression of cytokeratins (CKs) were included. The prevalence and pattern of expression for various CKs were assessed and details of tumours negative for CKs were collected. A diagnostic approach based on our experience is provided. Forty-seven cases (34%) showed foci of conventional type invasive breast carcinoma or ductal carcinoma in situ (DCIS), while 93 cases (66%) were diagnosed as MBC based on morphology and/or CK expression. Ninety-seven cases (69%) were negative for one or more CKs, with 18 cases (13%) negative for five or more CKs. Eight cases (6%) lacked expression of all CKs tested. Further examination showed evidence of carcinomatous nature in five cases, and three were diagnosed as MBC following extensive diagnostic work-up and based on our experience. CONCLUSION: This study suggests that MBC represents a spectrum of neoplasms, with some lacking CK expression. Sarcomatoid neoplasms of the breast lacking evidence of carcinomatous morphology and CK expression may represent an extreme end of differentiation that can be considered as carcinomas rather than sarcomas for management purposes (following extensive work-up).
Asunto(s)
Neoplasias de la Mama , Adulto , Biomarcadores de Tumor/análisis , Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Intraductal no Infiltrante/patología , Estudios de Cohortes , Diagnóstico Diferencial , Epitelio/patología , Femenino , Humanos , Inmunohistoquímica , Queratinas/análisis , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoma/diagnóstico , Sarcoma/patologíaRESUMEN
Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Asunto(s)
Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Neoplasias de la Mama Triple Negativas/patología , Antígeno B7-H1/inmunología , Biomarcadores de Tumor/inmunología , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Gestión de Riesgos , Neoplasias de la Mama Triple Negativas/inmunologíaRESUMEN
Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers. Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence. Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer/normas , Adulto , Factores de Edad , Anciano , Europa (Continente) , Femenino , Humanos , Mamografía/normas , Persona de Mediana Edad , Ultrasonografía Mamaria/normasRESUMEN
Trastuzumab has significantly improved the overall survival of patients with HER2+ metastatic breast cancer (MBC). However, outcomes can vary, with patients progressing within 1 year of treatment or exceptional cases of complete response to trastuzumab for ≥10 years. Identification of the underlying genomic aberrations of "exceptional responders (ExRs)" compared to "rapid non-responders (NRs)" increases our understanding of the mechanisms involved in MBC progression and identification of biomarkers of trastuzumab response and resistance. Whole-exome sequencing was performed on six ExRs compared to five NR. The overall fraction of genome copy number alteration (CNA) burden was higher in NR patients (P = 0.07), while more significantly pronounced in copy number gains (P = 0.03) in NR compared to ExRs. Delineation of the distribution of CNA burden across the genome identified a greater degree of CNA burden in NR within Chr8 (P = 0.02) and in Chr17 (P = 0.06) and conferred a statistically significant benefit in overall survival. Clinical trial number: NCT01722890 [ICORG 12/09].