Association between HER2 status in gastric cancer and clinicopathological features: a retrospective study using whole-tissue sections.

BACKGROUND: Gastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. Trastuzumab was recently approved for metastatic or locally advanced carcinomas arising in the stomach or in the gastroesophageal junction in patients with HER2-positive tumors. However, data on the frequency of HER2-positive cases among Brazilian patients are limited. Our aim was to characterize HER2 protein and gene status in a series of Brazilian patients with gastric cancer and to evaluate its association with clinicopathological data. METHODS: Histological slides from 124 primary gastrectomies were reviewed and their pathological reports were retrieved from the files at a Brazilian university hospital. Automated immunohistochemistry for HER2 was performed on whole-tissue sections from each tumor. HER2-equivocal cases by immunohistochemistry were submitted to automated dual in situ hybridization for gene amplification evaluation. HER2 status was confronted with clinicopathological parameters in order to assess statistically significant associations. RESULTS: Immunohistochemistry analysis revealed that 13/124 cases (10.5 %) were HER2 positive (3+), 10/124 cases (8.1 %) were equivocal (2+) and 101/124 cases (81.4 %) were negative, being 7 cases 1+. None of the equivocal cases showed gene amplification. The overall HER2 positivity rate was 10.5 %. There was an association between HER2 expression and Laurén's intestinal histological subtype (P = 0.048), well to moderately differentiated tumors (P = 0.004) and presence of lymphovascular invasion (P = 0.031). No association was found between HER2 status and tumor topography. CONCLUSIONS: Confronted with data published by other authors, the lower percentage of HER2-positive cases found in our series might be partially explained by the lower frequency of tumors arising at the gastroesophageal junction in comparison with distal gastric carcinomas in Brazilian patients. This could also account for the lack of statistically significant association between HER2 status and tumor topography in our study.

Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions.

PURPOSE: Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients' overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS. MATERIALS AND METHODS: IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS. RESULTS: Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B-like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor-positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS. CONCLUSION: NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

Evaluation of immunophenotype and inflammation in canine mammary neoplasms with solid arrangement.

Morphological and immunohistochemical studies of solid arrangement canine mammary carcinomas have shown that the different histological types may be characterized by proliferation of epithelial and/or myoepithelial cells. However, little is known about immunophenotypes and the importance of inflammation as prognostic factors in these neoplasms. The objective of the present study was to characterize the immunophenotype and degree of inflammation in the solid type of canine mammary neoplasm and to investigate their association with metastasis, Ki-67 index, tumour size, necrosis and survival. Sixty-five carcinomas with solid pattern, basaloid carcinomas, solid papillary carcinomas, malignant adenomyoepitheliomas (MAMEs) or malignant myoepitheliomas (MMEs) were investigated. Luminal A, luminal B HER2 negative and HER2 positive, HER2 overexpressed and triple negative immunophenotypes were immunolabelled as were Ki-67 protein and cyclooxygenase-2 (Cox-2). Histological peritumoural and intratumoural inflammatory infiltrates were graded (distribution × intensity) and the presence of necrosis identified. We found a statistical difference between histological types and immunophenotypes, with MME and MAME having a higher occurrence of luminal A, whereas most neoplasms had the luminal B HER-negative immunophenotype. There was no correlation between immunophenotype and degree of peri- and intratumoural inflammation, nodal metastasis, necrosis or tumour size. An increased degree of peri- and intratumoural inflammation was significantly associated with lymph node metastasis, and more severe intratumoural inflammation was associated with the presence of tumour necrosis. Tumour size, Ki-67 index and Cox-2 score were not associated with inflammation in either peri- or intratumoural regions. No difference was observed in survival in relation to immunophenotype or degree of inflammation, but the Cox regression model revealed that nodal metastasis influenced the risk of death.

Survival of patients with operable breast cancer (Stages I-III) at a Brazilian public hospital--a closer look into cause-specific mortality.

BACKGROUND: Breast cancer incidence is increasing. The survival rate varies and is longer in high-income countries. In Brazil, lower-income populations rely on the Unified Public Health System (Sistema Único de Saude, SUS) for breast cancer care. The goal of our study is to evaluate the survival of patients with operable breast cancer stages I-III at a Brazilian public hospital that treats mostly patients from the SUS. METHODS: A cohort study of patients who underwent surgery for breast cancer treatment at the Clinical Hospital of the Federal University of Minas Gerais from 2001 to 2008 was performed, with a population of 897 cases. Information on tumor pathology and staging, as well as patients' age and type of health coverage (SUS or private system) was collected. A probabilistic record linkage was performed with the database of the Mortality Information System to identify patients who died by December 31th, 2011. The basic cause of death was retrieved, and breast cancer-specific survival rates were estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis of factors related to survival. RESULTS: A total of 282 deaths occurred during the study's period, 228 of them due to breast cancer. Five-year breast cancer-specific survival rates were 95.5% for stage I, 85.1% for stage II and 62.1% for stage III disease. Patients from the SUS had higher stages at diagnosis (42% was in stage III, and from the private system only 17.6% was in this stage), and in the univariate but not multivariate analysis, being treated by the SUS was associated with shorter survival (hazard ratio, HR = 2.22, 95% CI 1.24-3.98). In the multivariate analysis, larger tumor size, higher histologic grade, higher number of positive nodes and age older than 70 years were associated with a shorter breast cancer-specific survival. CONCLUSIONS: Five-year breast cancer survival was comparable to other Brazilian cohorts. Patients treated by the SUS, rather than by the private system, had shorter survival times, mostly due to higher initial stage of the disease.

Can TILs be associated with prognostic factors and survival rates in breast cancer? A retrospective analysis

Introduction: The relationship between the tumor inflammatory infiltrate, also known as tumor-infiltrating lymphocytes (TILs), and invasive breast carcinomas has been extensively studied in recent years to verify its association with prognosis and response to treatment. The goal of this study was to associate the presence of TILs with patient's survival time. Methods: We studied prognostic clinicopathological characteristics already established in the literature and their impact on overall five-year survival time of patients with invasive breast cancer treated at Hospital Santa Casa in Belo Horizonte, Minas Gerais, Brazil, in 2011 (n=290). This was an observational and retrospective study. Results: The presence of TILs was associated with tumors of no special type (p=0.018) and with younger age of the patients (p=0.042). Smaller tumor size (HR: 19.24; 95%CI 4.30­86.15; p<0.001), absence of metastasis to the axillary lymph nodes (HR: 2.80; 95%CI 1.02­7.70; p=0.002), positivity for progesterone receptor (HR: 0.39; 95%CI 0.17­0.87; p=0.022), and presence of TILs (HR: 0.23; 95%CI 0.08­0.65; p=0.005) were associated with longer survival times. Conclusions: This study suggests that the presence of TILs, along with other clinicopathological characteristics, is a prognostic factor in breast cancer

Adjuvant Thalidomide and Metronomic Chemotherapy for the Treatment of Canine Malignant Mammary Gland Neoplasms.

BACKGROUND/AIM: The aim of the present study was to evaluate a multimodal approach for the treatment of canine malignant mammary gland neoplasms, including surgery, chemotherapy, thalidomide, and metronomic chemotherapy (MC). MATERIALS AND METHODS: Fifty-eight female dogs were submitted to four different treatments: surgery; surgery with chemotherapy; surgery with chemotherapy and thalidomide; and surgery with chemotherapy and metronomic chemotherapy and overall survival was evaluated. RESULTS: No statistical difference was found in the proliferative index and microvessel density of primary neoplasms and distant metastases following thalidomide treatment. Diffuse intense inflammatory infiltrate was predominant in primary tumors and diffuse moderate inflammatory infiltrate in metastatic lesions. No statistically significant difference was observed in median survival time (MST) between treatment groups when including all clinical stages (p=0.3177). However, animals diagnosed with distant metastasis treated with surgery and chemotherapy associated with thalidomide or MC presented longer MST when compared to animals treated only with surgery or surgery and chemotherapy (p<0.0001). CONCLUSION: The proposed multimodal therapy protocols including antiangiogenic and immunomodulatory therapies demonstrated a clinical benefit for patients in advanced clinical stages.

[Mortality pattern of Jewish community of Belo Horizonte in the 20th century]. / Padrão de mortalidade da comunidade judaica de Belo Horizonte no século XX.

OBJECTIVE: Genetic and environmental factors are known for their importance in the genesis of the majority of diseases. It is possible to study them through the observation of prevalence of diseases, and also the mortality causes, relating it to social habits and ethnic and familial origins of the individuals. In those studies, communities in which there are social and genetic links stand out. The Jewish community of Belo Horizonte fits these criteria. It has been consolidated in the 20th decade of the last century. Nowadays the Federação Israelita de Minas Gerais (FISEMG) has records of approximately 600 families. The purpose of this study is to define the mortality pattern in this community, and how it has changed since the community's formation. METHODS: Data was recovered from the files of the Instituto Histórico Israelita Mineiro, the FISEMG and from the cemeteries Israelita and Bonfim. RESULTS: 601 death registries have been studied, 61,6% belonging to men and 38,4% to women. The diseases of the circulatory system were the most frequent cause of death since the '40s, and infectious diseases, including tuberculosis, deserve note in the '30s and '40s. CONCLUSION: There was a change in death pattern of the Jewish community of Belo Horizonte.

Association between age and survival in a cohort of Brazilian patients with operable breast cancer.

Whether age is an independent prognostic factor in breast cancer is a matter of debate. This is a retrospective cohort study of 767 breast cancer patients, stages I-III, treated at the Hospital das Clínicas, Minas Gerais Federal University, Belo Horizonte, Minas Gerais State, Brazil, from 2001 to 2008, aiming to study the relationship between age and survival. We included variables related to patients, tumors, and types of treatment. Different sets of Cox models were used for survival analysis. Hazard ratios (HR) and 95%CI were calculated. The relationship between age and breast cancer survival did not change substantially in any of them. In the model that accounted for all variables, women aged 70 and older (HR = 1.51, 95%CI: 1.04-2.18), and 35 or younger (HR = 1.78, 95%CI: 1.05-3.01) had shorter cancer specific survival than patients aged between 36 and 69. In addition, older age, having at least one comorbidity, and being white were associated with a higher risk of dying from other causes. In conclusion, shorter breast cancer survival is expected among the youngest and oldest patients.

Bilateral axillary lymphadenopathy: differential diagnosis and management

Lymphonodopathy is an increase in volume and/or changes in the characteristics of lymph nodes, and it can be caused by benign or malignant diseases. Appropriate physical examination should define their clinical characteristics, and, if needed, complementary imaging or anatomopathological tests should be performed for diagnostic definition. In the present article, we report the case of a female patient, with sarcoidosis, who presented axillary lymph node disease, and the exams that followed until the diagnostic conclusion.

Co-Expression of p16, Ki67 and COX-2 Is Associated with Basal Phenotype in High-Grade Ductal Carcinoma In Situ of the Breast.

We assessed the co-expression of cell cycle-related biomarkers in a series of 121 consecutive cases of high-grade ductal carcinoma in situ (DCIS), pure or associated with invasive carcinoma, and their associations with the different immunoprofiles of DCIS. Cases were identified from the histopathology files of the Breast Pathology Laboratory, Federal University of Minas Gerais, Brazil, from 2003 to 2008. The expression of estrogen receptor, progesterone receptor, HER2 overexpression, cytokeratin 5, epidermal growth factor receptor 1, cyclooxygenase-2, p16 and Ki67 were assessed. Tumors were placed into five subgroups according to their immunohistochemical profile: luminal A, luminal B, HER2, basal-like and "not classified". We found that the basal phenotype was associated with a higher frequency of p16-positive cases (83%) and the luminal A phenotype showed a higher frequency of p16-negative cases (93%; p=0.000). The association of biomarkers p16(+)/Ki67(+)/COX2(+) was expressed in 02/06 cases (33.3%) of the basal phenotype but in only 01/70 cases (1.4%) of the luminal A phenotype (p=0.01). The co-expression of p16(+)/Ki67(+)/COX2(-) was associated with a basal phenotype (p=0.004). P16 expression, p16(+)/Ki67(+)/COX2(+) and p16(+)/Ki67(+)/COX2(-) co-expression showed significant associations with the basal phenotype and these profiles could be used to guide more aggressive treatment strategies in patients with high-grade DCIS.

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast.

BACKGROUND: This study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast. METHODS: A retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index. RESULTS: Weak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa=0.38), columnar cell hyperplasia (CCH; Kappa=0.32), while a moderate agreement (Kappa=0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa=0.62) and lobular carcinoma in situ (LCIS; Kappa=0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa=0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa=0.44), low-grade DCIS (Kappa=0.47), intermediate-grade DCIS (Kappa=0.45), and DCIS with microinvasion (Kappa=0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa=0.68). CONCLUSIONS: According to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725.

Ductal carcinoma in situ of the breast: correlation between histopathological features and age of patients.

BACKGROUND: The histopathological subtype, nuclear grade and presence or absence of comedonecrosis are established as critical elements in the reporting of ductal carcinoma in situ (DCIS) of the breast. The aims of this study were to determine the frequencies of morphological subtypes of DCIS, nuclear grade and comedonecrosis; to compare the age of patients with the histopathological characteristics of DCIS, and to assess the agreement of grade between in situ and invasive components in DCIS cases that were associated with invasive carcinoma. METHODS: We evaluated a series of 403 cases of DCIS, pure or associated with invasive mammary carcinoma, consecutively identified from the histopathology files of the Breast Pathology Laboratory, Federal University of Minas Gerais, Brazil, from 2003 to 2008. RESULTS: DCIS displayed a single growth pattern in most cases (55.1%) and the solid subtype was the most common morphology (42.2% of the total). High-grade DCIS was identified in 293/403 cases (72.7%) and comedonecrosis was present in 222/403 cases (55%). Among DCIS with a single architectural pattern, high grade was more common in the solid subtype (151/168 cases, 89.9%; p < 0.001). Only 32% of tumours with a cribriform pattern had high nuclear grade. Comedonecrosis was more common in the solid morphology than in the cribriform, papillary and micropapillary subtypes (p < 0.001). Patients with high-grade DCIS were younger in relation to patients with low-grade DCIS (p = 0.027) and patients with tumours with comedonecrosis were also younger in comparison to patients with tumours without comedonecrosis (p = 0.003). Fair agreement was observed between in situ and invasive components with regard to grade (weighted kappa = 0.23). CONCLUSIONS: The high nuclear grade and the presence of comedonecrosis were identified more frequently in younger patients and more often correlated with the solid pattern of DCIS. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_227.

High agreement between whole slide imaging and optical microscopy for assessment of HER2 expression in breast cancer: whole slide imaging for the assessment of HER2 expression.

UNLABELLED: Whole slide imaging (WSI) technology has been used for training, teaching, researching, and remote consultation. Few studies compared HER2 expression using optical microscopy (OM) and WSI evaluations in breast carcinomas. However, no consensus has been achieved comparing both assessments. MATERIAL AND METHODS: Sections from tissue microarray containing 200 preselected invasive breast carcinomas were submitted to immunohistochemistry applying three anti-HER2 antibodies (HercepTest™, CB11, SP3) and in situ hybridization (DDISH). Slides were evaluated using OM and WSI (Pannoramic MIDI and Viewer, 3DHISTECH). Sensitivity and specificity were calculated comparing the anti-HER2 antibodies and DDISH. RESULTS: WSI and OM HER2 evaluations agreement was considered good (SP3, k=0.80) to very good (CB11 and HercepTest™, k=0.81). WSI evaluation led to higher sensitivity (ranging from 100 of SP3 and HercepTest™ to 97 of CB11) and lower specificity (ranging from 86.4 of SP3 to 89.4 of HercepTest™) compared to OM evaluation (sensitivity ranged from 92.1 of CB11 to 98 of SP3 and specificity ranged from 95.2 of SP3 and HercepTest™ to 97.1 of CB11 and SP3). CONCLUSION: High agreement was achieved between WSI and OM evaluations. All three antibodies were highly sensitive and specific using both evaluations. WSI can be considered a useful tool for HER2 immunohistochemical assessment.

Intramuscular lipoma of the subscapularis muscle.

CONTEXT: Intramuscular lipomas are benign tumors that infiltrate the muscles. CASE REPORT: We describe the case of a 58-year-old female patient with an axillary lump. The lump was a lipoma inside the subscapularis muscle. It is important to differentiate these lesions from liposarcomas and from other diseases that may present as axillary lumps. The most accurate imaging method for differentiating benign lipomatous tumors from liposarcomas is magnetic resonance imaging, but surgical removal of these intramuscular lesions to confirm the diagnosis is recommended. CONCLUSION: Intramuscular lipomas are a rare cause of benign axillary lumps and should be considered in making differential diagnoses on axillary masses.

Immunohistochemical profile of high-grade ductal carcinoma in situ of the breast.

OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and "not classified". RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and "not classified" (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and "not classified" (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa=0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype.

[Consultation in breast surgical pathology: interobserver diagnostic variability of atypical intraductal proliferative lesions]. / Consultoria em patologia cirúrgica mamária: variabilidade interobservador no diagnóstico de lesões proliferativas intraductais atípicas.

PURPOSE: To evaluate the agreement about the histopathological diagnosis of intraductal proliferative breast lesions between general pathologists and a specialist in breast pathology. METHODS: This was an observational, cross-sectional study of 209 lesions received in consultation at the Breast Pathology Laboratory of the School of Medicine, Federal University of Minas Gerais, from 2007 to 2011, comparing the original diagnosis and the review. We included only cases with a formal request for review and cases in which the original diagnosis or reviewer's diagnosis showed proliferative lesions, pure ductal carcinoma in situ, ductal carcinoma in situ associated with microinvasion or associated with invasive carcinoma. The kappa index and percent concordance were used in the statistical analyses. RESULTS: A moderate agreement was observed between the original histopathological diagnosis and the second opinion (kappa=0.5; percentual concordance=83%). After the review, the diagnosis of malignancy was confirmed in 140/163 cases (86%) and the diagnosis of benign lesions was confirmed in 34/46 cases (74%). Regarding specific diagnosis, we observed moderate agreement between the original diagnosis and the reviewer's diagnosis (136/209 cases; kappa=0.5; percent concordance=65%). The highest disagreement was observed in cases of ductal carcinoma in situ with microinvasion (6/6 cases; 100%). Important discordance was observed in cases of atypical ductal hyperplasia (16/30 cases; 53%) and ductal carcinoma in situ (25/75 cases; 33%). Regarding the histological grade of ductal carcinoma in situ, we observed good agreement between the original diagnosis and the review (29/39 cases; kappa=0.6, percent agreement=74%). CONCLUSION: Our data confirm that intraductal proliferative breast lesions, especially atypical ductal hyperplasia, ductal carcinoma in situ and ductal carcinoma in situ with microinvasion show relevant discrepancies in the histopathological diagnoses, which may induce errors in therapeutic decisions.

False positivity in HER2 testing of breast cancer: novel paths for approaching an old dilemma.

AIMS: Variability in determining HER2 status has been reported, especially, differences in sensitivity and specificity among commercially available antibodies, with false positive and false negative results. We compared the sensitivity and specificity of five anti-HER2 antibodies by immunohistochemistry (IHC), using the new dual colour brightfield in situ hybridisation (DDISH) as the gold standard, on invasive breast carcinomas (IBC) arrays. MATERIAL AND METHODS: Serial sections from tissue microarrays (TMA) containing 200 preselected primary IBC were submitted to DDISH (VENTANA INFORM HER2 Dual ISH assay), and immunohistochemistry, using Dako A0485 and HercepTest (polyclonal), Novocastra CB11 (mouse monoclonal), NeoMarkers SP3 and Ventana 4B5 (rabbit monoclonal). RESULTS: From the initial 200 cases, 184 were assessed by DDISH and IHC. The concordance among the antibodies was considered very good (kappa statistics varied from 0.82 to 0.9). The overall concordance between IHC and DDISH ranged from 94.1% for CB11 to 96.6% for A0485. The antibodies A0485, HercepTest, SP3 and 4B5 were over 95% sensitive and specific. CB11 was the most specific antibody (97.1%). 60% (CB11) to 83.3% (SP3) of the 2+ cases showed no gene amplification by DDISH. False negative cases varied from 0.5% (A0485) to 3.8% (CB11) of the cases, and false positive from 1.6% (CB11) to 2.7% (HercepTest, SP3 and 4B5) of the 184 cases. CONCLUSIONS: There was very good agreement among the five anti-HER2 antibodies. CB11 was the most specific antibody, but showed more false negative cases. A0485, SP3, 4B5 and HercepTest were highly sensitive and specific, but showed more false positive cases.

Changes in mastectomy rates at a Brazilian public hospital over 20 years (1989 to 2008).

CONTEXT AND OBJECTIVE: Recently, breast-conserving surgery (BCS) has been replacing mastectomy for breast cancer treatment. The aim of this study was to evaluate the changes in mastectomy and BCS rates and the factors relating to these shifts. DESIGN AND SETTING: A retrospective study in a Brazilian public hospital. METHODS: Pathological records from female patients who underwent surgery for breast cancer at Hospital das Clínicas, Universidade Federal de Minas Gerais (HC-UFMG), between 1989 and 2008 were reviewed. The mastectomy and BCS rates were calculated. The chi-square test was used to assess factors associated with type of surgical treatment and to compare trends in treatment type over the years. Logistic regression was used for multivariate analysis. RESULTS: From 1989 to 2008, 2050 breast cancer surgical specimens were received in our service, corresponding to 1973 patients; 1324 (64.6%) of them were from mastectomy and 726 (35.4%) from BCS. A shift from mastectomy towards BCS was observed (P < 0.001). In multivariate analysis, earlier year of surgery (P < 0.001), larger tumor size (P < 0.001), having at least one positive axillary lymph node (P < 0.001) and patients' age greater than 68 years (P = 0.007) were predictors of mastectomy. CONCLUSIONS: There was a shift from mastectomy towards BCS in our institution over the years. This may reflect consolidation of BCS (plus radiotherapy) as an equivalent treatment to mastectomy in terms of survival and a shift to earlier diagnosis for the disease.

Lobular neoplasia: frequency and association with other breast lesions.

BACKGROUND: Using new molecular biology techniques, recent studies have implicated a common evolutionary pathway between lobular neoplasia, lobular carcinomas, and columnar cell lesions. Our aims were to assess the frequency of lobular neoplasia in a series of breast biopsies that were performed and examined in the same institution and to analyze the association between subtypes of lobular neoplasia and benign and malignant breast lesions. METHODS: Cases were selected after reviewing archived pathological reports in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais (1999-2008). Cases of lobular neoplasia were reviewed and classified as atypical lobular hyperplasia, ductal involvement by cells of atypical lobular hyperplasia, lobular carcinoma in situ, and pleomorphic lobular carcinoma in situ. Coexistence of lobular neoplasia with other breast lesions, including columnar cell lesions, invasive ductal carcinoma and invasive lobular carcinoma, was evaluated. The association between lobular neoplasia and breast lesions was analyzed by Fisher's exact test and chi-square test for linear trend. RESULTS: We analyzed 5650 breast specimens, selecting 135 breast specimens (2.4%) that had a diagnosis of lobular neoplasia, corresponding to 106 patients. Hematoxylin and eosin-stained slides were available for 84 cases, 5 of which were excluded because they contained only "indeterminate" in situ lesions. Of the 79 remaining cases, columnar cell lesions were present in 78.5%, primarily with columnar cell changes without atypia (67.7%). Invasive carcinoma was present in 45.6% of cases of lobular neoplasia--a similar frequency (47.2%) as invasive ductal carcinoma and invasive lobular carcinoma. We noted a significant linear trend (p < 0.03) of a higher frequency of invasive carcinomas that were concomitant with lobular carcinoma in situ compared with atypical lobular hyperplasia. Invasive lobular carcinomas were associated with lobular carcinoma in situ in 33% of cases, compared with 2.8% of atypical lobular hyperplasia cases. CONCLUSIONS: Our findings confirm a frequent association between lobular neoplasia and columnar cell lesions, the majority of which lacked atypia. We also observed a greater frequency of invasive carcinoma, more commonly invasive lobular carcinoma, associated with more developed forms of lobular neoplasia (lobular carcinoma in situ).

Association between age and survival in a cohort of Brazilian patients with operable breast cancer / Associação entre idade e sobrevida em uma coorte de pacientes brasileiras com câncer de mama operável / Asociación entre edad y supervivencia en una cohorte de pacientes brasileñas con cáncer de mama operable

Whether age is an independent prognostic factor in breast cancer is a matter of debate. This is a retrospective cohort study of 767 breast cancer patients, stages I-III, treated at the Hospital das Clínicas, Minas Gerais Federal University, Belo Horizonte, Minas Gerais State, Brazil, from 2001 to 2008, aiming to study the relationship between age and survival. We included variables related to patients, tumors, and types of treatment. Different sets of Cox models were used for survival analysis. Hazard ratios (HR) and 95%CI were calculated. The relationship between age and breast cancer survival did not change substantially in any of them. In the model that accounted for all variables, women aged 70 and older (HR = 1.51, 95%CI: 1.04-2.18), and 35 or younger (HR = 1.78, 95%CI: 1.05-3.01) had shorter cancer specific survival than patients aged between 36 and 69. In addition, older age, having at least one comorbidity, and being white were associated with a higher risk of dying from other causes. In conclusion, shorter breast cancer survival is expected among the youngest and oldest patients.

É discutível se idade é um fator prognóstico independente para câncer de mama. Conduzimos uma coorte retrospectiva de 767 pacientes com câncer de mama, estádios I-III, tratadas no Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil, de 2001 a 2008, para estudar a relação entre idade e sobrevida. Incluímos variáveis relacionadas às pacientes, aos tumores e ao tratamento. Diferentes conjuntos de modelos de Cox foram construídos. As razões de risco (RR) e IC95% foram calculados. A relação entre idade e sobrevida por câncer de mama não foi alterada substancialmente entre os modelos de Cox. No modelo com todas as variáveis explicativas, as mulheres de 70 anos ou mais (RR = 1,51; IC95%: 1,04-2,18) e até 35 anos (RR = 1,78; IC95%: 1,05-3,01) tiveram sobrevida causa-específica mais curta que as de 36-69 anos. Idades a partir de 70 anos, ter ao menos uma comorbidade e ser branca foram associadas a risco maior de óbito por outras causas. Em conclusão, as pacientes mais jovens e as mais idosas parecem ter sobrevida mais curta por câncer de mama.

Es discutible si la edad es un factor pronóstico independiente para el cáncer de mama. Se realizó sobre una cohorte retrospectiva de 767 pacientes con cáncer de mama, etapas I-III, atendidas en el Hospital de Clínicas, Universidad Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil, entre 2001 y 2008, para estudiar la relación entre edad y supervivencia. Incluimos variables relacionadas con las pacientes, los tumores y el tratamiento. Se construyeron diferentes conjuntos de modelos de Cox. Se calcularon los cocientes de riesgo (CR) e IC95%. La relación entre edad y supervivencia del cáncer de mama no ha cambiado substancialmente en los modelos. En el modelo con todas las variables, las mujeres de 70 años o más (CR = 1,51; IC95%: 1,04-2,18) y 35 años o menos (CR = 1,78; IC95%: 1,05-3,01) tuvieron menor supervivencia por cáncer de mama que las de 36 a 69 años. Tener edad avanzada, al menos una comorbilidad, y ser de piel blanca se asociaron a un mayor riesgo de morir por otras causas. En conclusión, las mujeres más jóvenes y las mayores parecen tener menor supervivencia de cáncer de mama.