Diretriz brasileira para detecção precoce do câncer de mama: desafios para implantação / Brazilian breast cancer early detection guideline: challenges for implementation

Objetivo: Avaliar o acesso e a adesão da população feminina, atendida pelo Sistema Único de Saúde (SUS), à Diretriz Brasileira de Detecção Precoce do Câncer de Mama, em duas cidades de médio porte de uma região metropolitana do estado de São Paulo, Brasil. Métodos: Estudo transversal. Os dados foram coletados no Sistema de Informação do Câncer (Siscan) e nas Secretarias Municipais de Saúde no período de 01/01 a 31/12 de 2017. Resultados: Em Santa Bárbara d'Oeste, foram realizadas 3.106 mamografias: 2.931 (94,4%) BI-RADS® 1-2; 21 (0,7%) BI-RADS® 3; 12 (0,4%) BI-RADS® 4-5; 142 (4,5%) BI-RADS® 0. A maioria dos exames (1.855 ­ 59,7%) foi realizada em mulheres de 50 a 69 anos. A cobertura mamográfica na população de risco foi de 11,2%. O envelhecimento foi relacionado ao BI-RADS® 4-5 (p = 0,005). A idade jovem esteve relacionada ao maior número de BI-RADS® 0 (p = 0,03). Em Vinhedo, foram realizadas 1.996 mamografias: 1.835 (91,9%) BI-RADS® 1-2; 9 (0,45%) BI-RADS® 3; 7 (0,35%) BI-RADS® 4-5; 145 (7,3%) BI-RADS® 0. A maioria dos exames (975 ­ 48,8%) foi realizada em mulheres de 50-69 anos. A população coberta pela mamografia foi de 17%. Reunindo ambas as análises populacionais, evidenciou-se que o envelhecimento esteve relacionado ao maior número de casos suspeitos (p = 0,007). Conclusão: A maioria das mamografias foi realizada em mulheres de 50-69 anos. A cobertura mamográfica ficou aquém da encontrada no Brasil e recomendada pela Organização Mundial da Saúde.

Objective: To evaluate the access and adherence of the female population, assisted by Health Unic System (SUS), to Brazilian Breast Cancer Early Detection Guideline in two medium-sized cities of a metropolitan region in the State of São Paulo, Brazil. Methods: Cross-sectional study. Data were collected from the Cancer Information System (Siscan) and from the Municipal Health Secretariats between 01/01 to 12/31, 2017. Results: In Santa Bárbara d'Oeste 3,106 mammograms were performed: 2,931 (94.4%) BI-RADS® 1-2; 21 (0.7%) BI-RADS® 3; 12 (0.4%) BI-RADS® 4-5; 142 (4.5%) BI-RADS® 0. Most of the exams (1,855 ­ 59.7%) among women aged 50-69 years. The mammographic coverage at risk population was 11.2%. Aging was related to BI-RADS® 4-5 (p = 0.005). The young age was related to the highest number of BI-RADS® 0 (p = 0.03). In Vinhedo 1,996 mammograms were performed: 1,835 (91.9%) BI-RADS® 1-2; 9 (0.45%) BI-RADS® 3; 7 (0.35%) BI-RADS® 4-5; 145 (7.3%) BI-RADS® 0. Most of the exams (975 ­ 48.8%) among women aged 50-69 years. The population covered by mammography was 17%. Gathering both population analysis, it was shown that aging was related to the highest number of suspected cases (p = 0.007). Conclusion: Most mammograms were performed between 50-69 years. Mammographic coverage fell short of that found in Brazil and recommended by the World Health Organization.

Potential impact of the z0011 trial on the omission of axillary dissection: a retrospective cohort study / Potencial impacto do estudo Z0011 na omissão da adenectomia axilar: Estudo de coorte retrospectiva

Abstract Objective To evaluate the number of patients with early-stage breast cancer who could benefit from the omission of axillary surgery following the application of the Alliance for Clinical Trials in Oncology (ACOSOG) Z0011 trial criteria. Methods A retrospective cohort study conducted in the Hospital da Mulher da Universidade Estadual de Campinas. The study population included 384 women diagnosed with early-stage invasive breast cancer, clinically negative axilla, treated with breast-conserving surgery and sentinel lymph node biopsy, radiation therapy, chemotherapy and/or endocrine therapy, from January 2005 to December 2010. The ACOSOG Z0011 trial criteria were applied to this population and a statistical analysis was performed to make a comparison between populations. Results A total of 384 patients underwent breast-conserving surgery and sentinel lymph node biopsy. Of the total number of patients, 86 women underwent axillary lymph node dissection for metastatic sentinel lymph nodes (SNLs). One patient underwent axillary node dissection due to a suspicious SLN intraoperatively, thus, she was excluded fromthe study. Among these patients, 82/86 (95.3%) had one to two involved sentinel lymph nodes andmet the criteria for the ACOSOG Z0011 trial with the omission of axillary lymph node dissection. Among the 82 eligible women, there were only 13 cases (15.9%) of lymphovascular invasion and 62 cases (75.6%) of tumors measuring up to 2 cm in diameter (T1). Conclusion The ACOSOG Z0011 trial criteria can be applied to a select group of SLNpositive patients, reducing the costs and morbidities of breast cancer surgery.

Resumo Objetivo Avaliar o número de pacientes com câncer de mama em estágio inicial que se beneficiariam da omissão da linfadenectomia axilar segundo o protocolo Z0011 da Alliance for Clinical Trials in Oncology (ACOSOG). Métodos Estudo de coorte retrospectiva conduzido no Hospital da Mulher da Universidade Estadual de Campinas. Foram incluídas mulheres diagnosticadas com carcinoma invasivo de mama em estágio inicial, com axila clinicamente negativa, tratadas com cirurgia conservadora e biópsia do linfonodo sentinela, radioterapia, quimioterapia e/ou hormonioterapia, de janeiro de 2005 a dezembro de 2010. Os critérios do estudo da ACOSOG Z0011 foram aplicados a essas mulheres e foi realizada uma análise estatística que comparou ambas as populações dos estudos. Resultados Foram estudadas 384 mulheres submetidas a cirurgia conservadora de mama e biópsia do linfonodo sentinela. Entre elas, 86 mulheres foram submetidas a linfadenectomia axilar por metástase presente no linfonodo sentinela. Uma paciente foi submetida a linfadenectomia axilar por ter um linfonodo palpável suspeito no intraoperatório, não incluída no estudo. Entre essas 86 pacientes, 82 (95,3%) tiveram de 1 a 2 linfonodos sentinela comprometidos e seriam elegíveis para omissão da linfadenectomia axilar pelos critérios do ACOSOG Z0011. Entre as 82 pacientes elegíveis, apenas 13 (15,9%) delas apresentaram tumores com invasão angiolinfática, e 62 (75,6%) dos tumores mediram até 2 cm (T1). Conclusão Os critérios do estudo ACOZOG Z0011 podem ser aplicados a um seleto grupo de pacientes com linfonodo sentinela positivo reduzindo os custos e a morbidade cirúrgica do tratamento do câncer de mama.

Potential Impact of the Z0011 Trial on the Omission of Axillary Dissection: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the number of patients with early-stage breast cancer who could benefit from the omission of axillary surgery following the application of the Alliance for Clinical Trials in Oncology (ACOSOG) Z0011 trial criteria. METHODS: A retrospective cohort study conducted in the Hospital da Mulher da Universidade Estadual de Campinas. The study population included 384 women diagnosed with early-stage invasive breast cancer, clinically negative axilla, treated with breast-conserving surgery and sentinel lymph node biopsy, radiation therapy, chemotherapy and/or endocrine therapy, from January 2005 to December 2010. The ACOSOG Z0011 trial criteria were applied to this population and a statistical analysis was performed to make a comparison between populations. RESULTS: A total of 384 patients underwent breast-conserving surgery and sentinel lymph node biopsy. Of the total number of patients, 86 women underwent axillary lymph node dissection for metastatic sentinel lymph nodes (SNLs). One patient underwent axillary node dissection due to a suspicious SLN intraoperatively, thus, she was excluded from the study. Among these patients, 82/86 (95.3%) had one to two involved sentinel lymph nodes and met the criteria for the ACOSOG Z0011 trial with the omission of axillary lymph node dissection. Among the 82 eligible women, there were only 13 cases (15.9%) of lymphovascular invasion and 62 cases (75.6%) of tumors measuring up to 2 cm in diameter (T1). CONCLUSION: The ACOSOG Z0011 trial criteria can be applied to a select group of SLN-positive patients, reducing the costs and morbidities of breast cancer surgery.

OBJETIVO: Avaliar o número de pacientes com câncer de mama em estágio inicial que se beneficiariam da omissão da linfadenectomia axilar segundo o protocolo Z0011 da Alliance for Clinical Trials in Oncology (ACOSOG). MéTODOS: Estudo de coorte retrospectiva conduzido no Hospital da Mulher da Universidade Estadual de Campinas. Foram incluídas mulheres diagnosticadas com carcinoma invasivo de mama em estágio inicial, com axila clinicamente negativa, tratadas com cirurgia conservadora e biópsia do linfonodo sentinela, radioterapia, quimioterapia e/ou hormonioterapia, de janeiro de 2005 a dezembro de 2010. Os critérios do estudo da ACOSOG Z0011 foram aplicados a essas mulheres e foi realizada uma análise estatística que comparou ambas as populações dos estudos. RESULTADOS: Foram estudadas 384 mulheres submetidas a cirurgia conservadora de mama e biópsia do linfonodo sentinela. Entre elas, 86 mulheres foram submetidas a linfadenectomia axilar por metástase presente no linfonodo sentinela. Uma paciente foi submetida a linfadenectomia axilar por ter um linfonodo palpável suspeito no intraoperatório, não incluída no estudo. Entre essas 86 pacientes, 82 (95,3%) tiveram de 1 a 2 linfonodos sentinela comprometidos e seriam elegíveis para omissão da linfadenectomia axilar pelos critérios do ACOSOG Z0011. Entre as 82 pacientes elegíveis, apenas 13 (15,9%) delas apresentaram tumores com invasão angiolinfática, e 62 (75,6%) dos tumores mediram até 2 cm (T1). CONCLUSãO: Os critérios do estudo ACOZOG Z0011 podem ser aplicados a um seleto grupo de pacientes com linfonodo sentinela positivo reduzindo os custos e a morbidade cirúrgica do tratamento do câncer de mama.

Power Doppler Ultrasonography and Shear Wave Elastography as Complementary Imaging Methods for Suspected Local Breast Cancer Recurrence.

OBJECTIVES: To prospectively investigate the diagnostic accuracy and clinical consequences of power Doppler morphologic criteria and shear wave elastography (SWE) as complementary imaging methods for evaluation of suspected local breast cancer recurrence in the ipsilateral breast or chest wall. METHODS: Thirty-two breast masses with a suspicion of local breast cancer recurrence on B-mode ultrasonography underwent complementary power Doppler and SWE evaluations. Power Doppler morphologic criteria were classified as avascular, hypovascular, or hypervascular. Shear wave elastography was classified according to a 5-point scale (SWE score) and SWE maximum elasticity. Diagnostic accuracy was assessed by the sensitivity, specificity, and area under the curve. A decision curve analysis assessed clinical consequences of each method. The reference standard for diagnosis was defined as core needle or excisional biopsy. RESULTS: Histopathologic examinations revealed 9 (28.2%) benign and 23 (71.8%) malignant cases. Power Doppler ultrasonography (US) had sensitivity of 34.8% (95% confidence interval [CI], 6.6%-62.9%) and specificity of 45.4% (95% CI, 19.3%-71.5%). The SWE score (≥3) had sensitivity of 87.0% (95% CI, 66.4%-97.2%) and specificity of 44.4% (95% CI, 13.7%-78.8%). The SWE maximum elasticity (velocity > 6.5cm/s) had sensitivity of 87% (95% CI, 66.4%-97.2%) and specificity of 77.8% (95% CI, 40.0% to 97.2%). The areas under the curves for the SWE score and SWE maximum elasticity were 0.71 (95% CI, 0.53-0.87) and 0.82 (95% CI, 0.64-0.93), respectively (P = .32). CONCLUSIONS: Power Doppler US is unsuitable for discrimination between local breast cancer recurrence and fibrosis. Although the SWE score and SWE maximum elasticity can make this discrimination, the use of these methods to determine biopsy may lead to poorer clinical outcomes than the current practice of performing biopsies of all suspicious masses.

Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer.

Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. José Aristodemo Pinotti Women's Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T (tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation.

Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer / Subtipos moleculares de câncer de mama não estão associados ao subestadiamento ou ao superestadiamento do câncer de mama

Abstract Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. José Aristodemo Pinotti Women's Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T ( tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation.

Resumo Objetivo avaliar a concordância entre o estadiamento clínico e patológico do câncer de mama em função das características clínicas e moleculares das pacientes. Métodos estudo de corte transversal, sendo coletados dados clínicos, epidemiológicos e anátomo-patológicos de 226 pacientes operadas no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti (Centro de Atenção Integral à Saúde da Mulher - CAISM/ Unicamp), de janeiro de 2008 a setembro de 2010. As pacientes foram estadiadas clínica e patologicamente e classificadas como: subestadiadas, quando o estadiamento clínico foi menor do que o patológico; corretamente estadiadas, quando o estadiamento clínico foi equivalente ao patológico; e superestadiadas, quando o estadiamento clínico foi maior do que o patológico. Resultados as pacientes subestadiadas eram mais jovens (52,2 anos; p < 0,01) e sintomáticas ao diagnóstico (p = 0,04) do que as pacientes corretamente estadiadas ou superestadiadas. O subtipo clinico-patológico, o status menopausal, a paridade, a terapia de reposição hormonal e a histologia não foram associados com a diferença no estadiamento. Detectamos que as mulheres com menos de 57 anos de idade foram clinicamente subestadiadas principalmente devido à subestimação do T (p < 0 ,001), assim como as mulheres na pré-menopausa (p < 0,01). Por outro lado, as pacientes cujo diagnóstico foi realizado por queixa clínica, e não rastreamento, foram clinicamente subestadiadas devido à subestimação do N (p < 0,001). Conclusão o estudo nos mostra que o subtipo clinico-patológico não está associado a diferenças de estadiamento, enquanto mulheres mais jovens, e que tiveram seu diagnóstico por queixa clínica, tendem a ter seus tumores mais frequentemente subestadiados.

Cysts within Otherwise Probably Benign Solid Breast Masses and the Risk of Malignancy.

Objective The objective of this study is to assess whether the largest cyst diameter is useful for BI-RADS ultrasonography classification of predominantly solid breast masses with an oval shape, circumscribed margins, and largest axis parallel to the skin, which, except for the cystic component, would be likely classified as benign. Methods This study received approval from the local institutional review board. From March 2009 to August 2014, we prospectively biopsied 170 breast masses from 164 women. We grouped the largest cyst and mass diameters according to histopathological diagnoses. We used Student's t-test, linear regression, and the area under the receiver operating characteristic curve (AUC) for statistical assessment. Results Histopathological examination revealed 143 (84%) benign and 27 (16%) malignant masses. The mean largest mass diameter was larger among malignant (mean ± standard deviation, 34.1 ± 16.6 mm) than benign masses (24.7 ± 16.7 mm) (P < 0.008). The mean largest cyst diameter was also larger among malignant (9.9 ± 7.1 mm) than benign masses (4.6 ± 3.6 mm) (P < 0.001). Agreement between measurements of the largest mass and cyst diameters was low (R(2) = 0.26). AUC for the largest cyst diameter (0.78) was similar to the AUC for the largest mass diameter (0.69) (p = 0.2). A largest cyst diameter < 3, ≥ 3 to < 11, and ≥ 11 mm had a positive predictive value of 0, 15, and 52%, respectively. Conclusion A largest cystic component < 3 mm identified within breast masses that show favorable characteristics may be considered clinically inconsequential in ultrasonography characterization. Conversely, masses with a largest cystic component ≥ 3 mm should be classified as BI-RADS-US category 4.

Cysts within Otherwise Probably Benign Solid Breast Masses and the Risk of Malignancy / Cistos no interior de nódulo mamários benignos: risco de malignidade

Abstract Objective The objective of this study is to assess whether the largest cyst diameter is useful for BI-RADS ultrasonography classification of predominantly solid breast masses with an oval shape, circumscribed margins, and largest axis parallel to the skin, which, except for the cystic component, would be likely classified as benign. Methods This study received approval from the local institutional review board. From March 2009 to August 2014, we prospectively biopsied 170 breast masses from 164 women. We grouped the largest cyst and mass diameters according to histopathological diagnoses. We used Student's t-test, linear regression, and the area under the receiver operating characteristic curve (AUC) for statistical assessment. Results Histopathological examination revealed 143 (84%) benign and 27 (16%) malignant masses. The mean largest mass diameter was larger among malignant (mean standard deviation, 34.1 16.6 mm) than benign masses (24.7 16.7 mm) (P < 0.008). The mean largest cyst diameter was also larger among malignant (9.9 7.1 mm) than benign masses (4.6 3.6 mm) (P < 0.001). Agreement between measurements of the largest mass and cyst diameters was low (R2 = 0.26). AUC for the largest cyst diameter (0.78) was similar to the AUC for the largest mass diameter (0.69) ( p = 0.2). A largest cyst diameter < 3, 3 to < 11, and 11 mm had a positive predictive value of 0, 15, and 52%, respectively. Conclusion A largest cystic component < 3 mm identified within breast masses that show favorable characteristics may be considered clinically inconsequential in ultrasonography characterization. Conversely, masses with a largest cystic component 3 mm should be classified as BI-RADS-US category 4.

Resumo Objetivo Avaliar se o maior diâmetro do cisto é útil para a classificação ultrassonográfica BI-RADS de nódulos mamários predominantemente sólidos, com forma oval, margens circunscritas e maior eixo paralelo à pele que, exceto pela presença do componente cístico, seriam classificados como provavelmente benignos. Métodos Este estudo foi aprovado pelo Comitê de Ética local. De março de 2009 a agosto de 2014, 170 nódulos mamários de 164 mulheres foram prospectivamente biópsiados. As medidas do maior diâmetro do maior cisto e do maior diâmetro do nódulo foram agrupados de acordo com os diagnósticos histopatológicos. O teste t de Student, a regressão linear e a área sob a curva ROC (AUC) foram utilizados para a avaliação estatística. Resultados O exame histopatológico revelou 143 (84%) nódulos benignos e 27 (16%) nódulos malignos. A média da medida do maior diâmetro dos nódulos foi maior entre os nódulos malignos (média desvio padrão, 34,1 16,6 mm) do que nos nódulos benignos (24,7 16,7 mm) (p < 0,008). A média do maior diâmetro do maior cisto também foi maior entre os nódulos malignos (9,9 7,1 mm) do que nos nódulos benignos (4,6 3,6 mm) (p < 0,001). A concordância entre as medidas dos maiores diâmetros dos nódulos e do maior diâmetro do maior cisto foi baixa (R2 = 0,26). A AUC do maior diâmetro do maior cisto (0,78) foi semelhante à AUC do maior diâmetro do nódulo (0,69) (p = 0,2). Os maiores diâmetros dos maiores cistos medindo < 3; 3 e < 11; e 11 mm tiveram um valor preditivo positivo de 0, 15 e 52%, respectivamente. Conclusão Componentes císticos < 3 mm identificados dentro de nódulos mamários que apresentam as demais características provavelmente benignas podem ser considerados clinicamente irrelevantes na caracterização ultrassonográfica. Por outro lado, nódulos que apresentam um componente cístico medindo 3 mm devem ser classificadas na categoria BI-RADS-US 4.

Cyclooxygenase-2 (COX2) and p53 protein expression are interdependent in breast cancer but not associated with clinico-pathological surrogate subtypes, tumor aggressiveness and patient survival.

UNLABELLED: In the last decade, different molecular subtypes of breast cancer have been proposed. Although displaying appreciable association with disease prognosis and the prognostic value of cytotoxic and endocrine therapeutic modalities, the subtypes seem to fail at completely explaining disease behavior and response to treatment. Molecules such as those of the cyclocooxigenase (COX) family, currently composed of three entities (COX 1, 2 and 3) have been shown to be associated with breast carcinogenesis, and the analysis of p53 expression in breast tumors may also offer some additional prognostic clues. Our study is aimed at assessing COX2 and p53 expression in these clinico-pathological surrogate subtypes, and to evaluate whether the expression of these molecules can help further explain the variability in prognosis still found within the clinico-pathological subtypes groups of breast cancer. METHODS: A total of 183 breast cancer samples were obtained from women treated at the Womens Hospital of Campinas State University, Campinas, Brazil, between June 2008 and January 2011. Immunohistochemistry was performed to detect the expression of ER, PR, ki67, COX2, and p53 and the HER2 status of the 183 specimens was assessed using FISH. Two COX2 staining thresholds were used to define COX2 positivity: low threshold (LT): moderate and intense staining were considered positive; high-threshold (HT): only intense staining was considered positive. RESULTS: There was no trend in COX2 overexpression from Luminal A-like to Triple-negative subtypes. By contrast, p53 was expressed in roughly 67% of the Luminal A-like tumors, 50% of the Luminal B-like HER2 positive tumors, 60.9% of the Luminal B-like HER2 negative, approximately 82% of the HER2 positive (non-luminal) and 87% of the Triple-negative tumors (p for trends=0.06). There was a significantly higher proportion of COX2 positive (LT) tumors (66.9%) when p53 was also positive compared to when the tumor was negative for p53 (in which case only18.0% of the tumors were positive for COX2; p<0.001). Neither marker was found to be associated with patients' survival. CONCLUSIONS: There seems to be a positive association between the expressions of COX2 and p53. Otherwise, neither the expression of COX nor that of p53 was associated with clinico-pathological subtypes, tumor features and prognosis. It seems to be too early to elect the detection of COX2 using IHC as prognostic or predictive tool, but incipient evidence points toward a possible role for the marker.

[The new classification of breast cancers: finding the luminal A]. / Nova classificação dos carcinomas da mama: procurando o luminal A.

PURPOSE: To compare the distributions of patients with clinical-pathological subtypes of luminal B-like breast cancer according to the 2011 and 2013 St. Gallen International Breast Cancer Conference Expert Panel. METHODS: We studied 142 women with breast cancer who were positive to estrogen receptor and had been treated in São Paulo state, southeast Brazil. The expression of the following receptors was assessed by immunohistochemistry: estrogen, progesterone (PR) and Ki-67. The expression of HER-2 was measured by fluorescent in situ hybridization analysis in tissue microarray. RESULTS: There were 29 cases of luminal A breast cancers according to the 2011 St. Gallen International Breast Cancer Conference Expert Panel that were classified as luminal B-like in the 2013 version. Among the 65 luminal B-like breast cancer cases, 29 (45%) were previous luminal A tumors, 15 cases (20%) had a Ki-67 >14% and were at least 20% PR positive and 21 cases (35%) had Ki-67 >14% and more than 20% were PR positive. CONCLUSIONS: The 2013 St. Gallen consensus updated the definition of intrinsic molecular subtypes and increased the number of patients classified as having luminal B-like breast cancer in our series, for whom the use of cytotoxic drugs will probably be proposed with additional treatment cost.

Nova classificação dos carcinomas da mama: procurando o luminal A / The new classification of breast cancers: finding the luminal A

OBJETIVO: Comparar a distribuição das pacientes segundo os subtipos clínico-patológicos de carcinomas de mama luminais like segundo o consenso de St. Gallen 2011 e 2013. MÉTODOS: Foram selecionadas 142 pacientes com carcinoma invasivo da mama que eram positivas para receptor de estrógeno, diagnosticadas e tratadas no estado de São Paulo, região Sudeste do Brasil. A expressão dos receptores de estrógeno, progesterona (RP) e Ki-67 foi avaliada por imunoistoquímica em microarranjo de tecidos. A expressão de HER-2 foi avaliada por hibridização fluorescente in situ. RESULTADOS: Observamos que 29 casos classificados como luminais A na classificação de St. Gallen 2011 eram luminais B na classificação de 2013. Dentre os 65 casos luminais B like da classificação de 2013, além dos 29 (45%) casos que migraram, observamos 15 casos (20%) com Ki-67 >14% e pelo menos 20% das células coradas; e 21 casos (35%) com Ki-67 >14% e RP positivo em mais de 20% das células coradas. CONCLUSÕES: Comparando a distribuição das pacientes com carcinomas luminais da mama segundo a classificação de St. Gallen 2011 e 2013 observamos que houve um aumento no número de carcinomas da mama luminais B like. Consequentemente, estima-se um aumento nas indicações de quimioterapia adjuvante e no custo do tratamento. .

PURPOSE: To compare the distributions of patients with clinical-pathological subtypes of luminal B-like breast cancer according to the 2011 and 2013 St. Gallen International Breast Cancer Conference Expert Panel. METHODS: We studied 142 women with breast cancer who were positive to estrogen receptor and had been treated in São Paulo state, southeast Brazil. The expression of the following receptors was assessed by immunohistochemistry: estrogen, progesterone (PR) and Ki-67. The expression of HER-2 was measured by fluorescent in situ hybridization analysis in tissue microarray. RESULTS: There were 29 cases of luminal A breast cancers according to the 2011 St. Gallen International Breast Cancer Conference Expert Panel that were classified as luminal B-like in the 2013 version. Among the 65 luminal B-like breast cancer cases, 29 (45%) were previous luminal A tumors, 15 cases (20%) had a Ki-67 >14% and were at least 20% PR positive and 21 cases (35%) had Ki-67 >14% and more than 20% were PR positive. CONCLUSIONS: The 2013 St. Gallen consensus updated the definition of intrinsic molecular subtypes and increased the number of patients classified as having luminal B-like breast cancer in our series, for whom the use of cytotoxic drugs will probably be proposed with additional treatment cost. .

Tissue aluminum concentration does not affect the genomic stability of ERBB2, C-MYC, and CCND1 genes in breast cancer.

It has long been hypothesized that body tissue uptake of aluminum may have biological implications in breast cancer. In vitro and in vivo studies have shown that aluminum may trigger genomic instability by interfering with DNA strands. The objective of this study was to examine the relationship between aluminum concentrations in the peripheral and central areas of breast tumors with the instability of three key genes in breast cancer, ERBB2, C-MYC, and CCND1 and aneuploidy of the chromosomes harboring these genes. Tissue samples of 118 women treated for breast cancer were obtained. Evaluation of aluminum content was carried out using graphite furnace atomic absorption spectrometry. A tissue microarray slide containing the tumor samples was used in FISH assays to assess ERBB2, C-MYC, and CCND1 expressions as well as the statuses of their respective chromosomes 17, 8, and 11. Clinicopathological data were obtained from patient's records. Aluminum levels of >2.0 mg/kg were found in 20.3 and 22.1% of the central and peripheral breast tumor areas, respectively. Amplification and/or aneuploid-positive statuses for ERBB2/CEP17, C-MYC/CEP8, and CCND1/CEP11 were detected in 24, 36.7, and 29.3% of the tumors, respectively. We found that aluminum concentration was not related to these altered gene statuses. Our findings suggest that aluminum concentration does not affect genomic stability in breast tissues. Tissue microenvironment modifications, due to the presence of aluminum compounds, seem more appealing as a possible target for future studies to determine the implications of aluminum in breast carcinogenesis.

Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues.

BACKGROUND: Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. METHODS: A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. RESULTS: The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). CONCLUSIONS: Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum concentration is related to the key genomic abnormalities associated with breast carcinogenesis.

HER2 expression in Brazilian patients with estrogen and progesterone receptor-negative breast carcinoma.

The aim of the study was to evaluate the relationship between clinical and pathological factors and survival in patients with double negative HER2-overexpressing carcinoma and triple negative carcinoma. One hundred and sixty-one (161) patients diagnosed with breast cancer negative for estrogen receptor (ER) and progesterone receptor (PR) were included. Of the total, 58 patients had double negative HER2-overexpressing (ER/PR-negative and HER2-positive) and 103 had triple negative (ER-negative, PR-negative and HER2-negative). ER and PR expression was assessed through immunohistochemistry (IHC) and HER2 expression was measured by immunohistochemistry and Fluorescent in situ Hybridization (FISH) analysis in tissue microarray. More than 80% had stages II and III disease and histologic grade III and nuclear grade 3. Patients with triple negative breast carcinoma had undifferentiated histologic types in 11% of cases and vascular invasion in 14.5%. Both groups had more than 50% visceral metastases. HER2 expression (p=0.42) and vascular invasion (p=0.05) did not interfere with survival. Survival of patients with Stages I-II disease was significantly longer than in those with Stage III disease both for double negative HER2-overexpressing carcinomas (p<0.0001) and triple negative carcinomas (p=0.03). The study shows that hormone receptor-negative breast carcinomas were undifferentiated and diagnosed at advanced stages and that HER2 expression was not associated with overall survival.

Expression of cyclooxygenase-2 (COX-2) and p53 in neighboring invasive and in situ components of breast tumors.

The aim of the study was to assess the relationship between the expression of COX-2 and p53, hormone receptors and HER-2 in the in situ (DCIS) and invasive components of ductal carcinomas (IDC) of the same breast. The expression of COX-2, p53, and hormone receptors was assessed in 87 cases of IDC with contiguous areas of DCIS. Results showed that there was no difference in COX-2 expression comparing the in situ and invasive components of the tumors. In the in situ component, there was a statistically borderline increase in p53 expression in tumors that also expressed COX-2. ER-positive specimens were more common in the group of tumors that expressed COX-2 in the invasive component. From this study we conclude that the expression of COX-2 was similar in the in situ and invasive components of the breast carcinomas. COX-2 positivity was marginally related with the expression of p53 in the in situ components, and with the ER expression in the invasive components.

[ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma]. / Expressão da proteína erbB-2 e dos receptores de hormônios na transição das regiões in situ para invasora de tumores da mama.

PURPOSE: to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). METHODS: Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5% (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. RESULTS: the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). CONCLUSIONS: our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.

Expressão da proteína erbB-2 e dos receptores de hormônios na transição das regiões in situ para invasora de tumores da mama / ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma

OBJETIVOS: avaliar a expressão de erbB-2 e dos receptores hormonais para estrógeno e progesterona (RE/RP) nas regiões de transição entre as frações in situ e invasoras de neoplasias ductais da mama (CDIS e CDI, respectivamente). MÉTODOS: oitenta e cinco casos de neoplasias mamárias, contendo regiões contíguas de CDIS e CDI, foram selecionados. Espécimes histológicos das áreas de CDIS e de CDI foram obtidos através da técnica de tissue microarray (TMA). As expressões da erbB-2 e dos RE/RP foram avaliadas por meio de imunoistoquímica convencional. A comparação da expressão da erbB-2 e dos RE/RP nas frações in situ e invasoras da mama foi realizada com emprego do teste de McNemar. Os intervalos de confiança foram determinados em 5 por cento (p=0,05). Foram calculados coeficientes de correlação intraclasse (ICC) para avaliar a concordância na tabulação cruzada da expressão de erbB-2 e RE/RP nas frações de CDIS e CDI. RESULTADOS: a expressão da erbB-2 não diferiu entre as áreas de CDIS e CDI (p=0,38). Comparando caso a caso suas áreas de CDIS e CDI, houve boa concordância na expressão da erbB-2 (coeficiente de correlação intraclasse, ICC=0,64), dos RP (ICC = 0,71) e dos RE (ICC = 0,64). Considerando apenas tumores cujo componente in situ apresentasse áreas de necrose (comedo), o ICC para erbB-2 foi de 0,4, comparado a 0,6 no conjunto completo de casos. Os ICC não diferiram substancialmente daqueles obtidos com o conjunto completo de espécimes em relação aos RE/RP: para RE, ICC=0,7 (versus 0,7 no conjunto completo), e para RP, ICC=0,7 (versus 0,6 no conjunto completo). CONCLUSÕES: nossos achados sugerem que as expressões de erbB-2 e RE/RP não diferem nos componentes contíguos in situ e invasivo em tumores ductais da mama.

PURPOSE: to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). METHODS: Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5 percent (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. RESULTS: the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). CONCLUSIONS: our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.

Comparative evaluation of the erbB2 and hormone receptor status of neighboring invasive and in situ components of ductal carcinomas of the breast.

BACKGROUND: It remains unknown whether erbB2 expression and hormone receptor status predict the invasive potential of ductal carcinoma in situ (DCIS) of the breast. OBJECTIVES: To examine erbB2 and estrogen/progesterone receptor (ER/PR) status in the precise areas where DCIS turns into invasive ductal carcinoma (IDC). SUBJECTS AND METHODS: Eighty-seven cases of breast malignancies harboring contiguous regions of DCIS and IDC were selected. Separate histological samples from the DCIS and the neighboring IDC were obtained using tissue microarrays. The erbB2 and ER/PR statuses were assessed using immunohistochemistry (erbB2 and ER/PR) and fluorescence in situ hybridization (FISH - only erbB2). RESULTS: The expression of erbB2 did not differ in the DCIS and IDC components of the breast tumors (p=0.35). There was good agreement in sample-by-sample comparisons of erbB2 (intraclass correlation coefficient [ICC]=0.78), PR (ICC=0.61) and ER (ICC=0.70) expression in the DCIS and IDC components. CONCLUSION: Our findings suggest that the expressions of erbB2 and ER/PR do not differ in the contiguous regions from DCIS to IDC.