Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma / Receptores HER2, compromiso ganglionar axilar y sobrevida en mujeres con cáncer de mama ductal invasivo

ABSTRACT Background: Breast cancer (BC) is the most common malignancy in women. Aim: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. Patients and Methods: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. Results: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. Conclusions: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.

Antecedentes: El cáncer de mama es el tumor maligno más común en mujeres. Objetivo: Conocer el impacto del estado HER2 sobre el compromiso ganglionar axilar al momento del diagnóstico y durante los primeros cuatro años después de la cirugía en mujeres con carcinoma ductal invasivo de tipo no especial (IDC-NST). Pacientes y Métodos: Incluimos retrospectivamente a 375 mujeres en etapas clínicas iniciales de IDC-NST que fueron operadas en un hospital clínico. Ellas se dividieron en grupos de acuerdo al fenotipo: HR+HER2-, HR+HER2+, HR-HER2+y HR-HER2-. La disección de ganglios axilares se efectuó solo en las pacientes con macrometástasis en el ganglio centinela. Si había más de tres ganglios comprometidos, se efectuó radioterapia. Todas las pacientes se trataron con quimioterapia. Las pacientes HER2+ recibieron trastuzumab y las pacientes HR+ recibieron hormonoterapia. Resultados: Tumores más grandes, de mayor grado de malignidad, HR+, HER2+ y la invasión linfovascular fueron predictivos de la presencia de metástasis axilares al momento del diagnóstico. La sobrevida más baja se observó en pacientes HR-HER2+. La sobrevida libre de recurrencia locorregional más baja, se observó en pacientes HR-HER2+ y HR-HER2-. HER2 no fue predictor de sobrevida. Conclusiones: En estas mujeres, HER2+fue predictor de la presencia de compromiso ganglionar axilar al momento del diagnóstico pero no de la sobrevida a cuatro años.

Adjuvant treatment delay in breast cancer patients / Atraso no tratamento adjuvante em pacientes com câncer de mama

Summary Background: to evaluate if time between surgery and the first adjuvant treatment (chemotherapy, radiotherapy or hormone therapy) in patients with breast cancer is a risk factor for lower overall survival (OS). Method: data from a five-year retrospective cohort study of all women diagnosed with invasive breast cancer at an academic oncology service were collected and analyzed. Results: three hundred forty-eight consecutive women were included. Time between surgery and the first adjuvant treatment was a risk factor for shorter overall survival (HR=1.3, 95CI 1.06-1.71, p=0.015), along with negative estrogen receptor, the presence of lymphovascular invasion and greater tumor size. A delay longer than 4 months between surgery and the first adjuvant treatment was also associated with shorter overall survival (cumulative survival of 80.9% for delays ≤ 4 months vs. 72.6% for delays > 4 months; p=0.041, log rank test). Conclusion: each month of delay between surgery and the first adjuvant treatment in women with invasive breast cancer increases the risk of death in 1.3-fold, and this effect is independent of all other well-established risk factors. Based on these results, we recommend further public strategies to decrease this interval.

Resumo Objetivo: avaliar se o tempo da cirurgia até o primeiro tratamento adjuvante (quimioterapia, radioterapia ou hormonioterapia) em pacientes com câncer de mama é um fator de risco para pior sobrevivência global (SG). Métodos: estudo retrospectivo em que foram coletados dados dos prontuários de todas as mulheres com câncer de mama invasivo, diagnosticadas entre janeiro de 2005 e dezembro de 2010, atendidas consecutivamente em um serviço acadêmico de oncologia. Resultados: foram incluídas 348 mulheres, com mediana de tempo entre a cirurgia e o primeiro tratamento adjuvante de 2 meses. A sobrevivência global foi pior entre as mulheres com maior tempo entre a cirurgia e o primeiro tratamento adjuvante. Após análise multivariada, essa variável permaneceu como fator de risco independente para SG, juntamente com receptor de estrógeno negativo, presença de invasão angiolinfática e maior tamanho tumoral. Conclusão: o tempo entre a cirurgia e o primeiro tratamento adjuvante é um fator de risco independente para a sobrevivência global de mulheres com câncer de mama invasivo.

Cáncer de mama en mujeres adultas mayores, características clínicas e histopatológicas y resultados del tratamiento con intención curativa / Characteristics and results of breast cancer in elderly females treated with curative inten

Background: Aging is the main risk factor to acquire breast cancer (BC). Nevertheless BC in elderly patients is sub-represented in clinical trials. Aim: To describe the clinical characteristics and long term treatment results of localized BC in older women. Material and Methods: Review of medical records of 65 women aged 70 to 88 years, with localized BC, treated with surgery, postoperative radiotherapy or systemic therapy at a Clinical Hospital in Chile. Results: The presence of symptoms or abnormal findings on physical examination were the main reasons for consulting in 65% of cases. Compared with tumors detected on physical examination, those detected using screening mammogram were smaller and were in stage 1 with a higher frequency (18 and 59% respectively, p < 0.01). The pathological type was luminal in 80% of cases. Overall survival was better for luminal pathological type. All patients completed radiotherapy without interruptions developing minor acute toxicity. The most common co-morbidity was high blood pressure occurring in 46% of patients. Thirteen percent of patients had three or more co-morbidities. After a median follow up of 7 years, 23 (35%) patients had died and the cause of death was BC in 43% of cases. Two patients died of lung cancer. No patient had a local breast relapse. Conclusions: Screening mammogram in older women detected smaller tumors and it was associated with a better survival. BC is the ultimate cause of death in approximately half of cases.

Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast.

BACKGROUND: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables. RESULTS: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively) without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively). The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021). CONCLUSIONS: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.

A long-term survival pattern for breast cancer treated in a single institution.

Aim: This paper presents a 14-year retrospective study evaluating the survival rates and prognostic factors of breast carcinoma patients treated in private treatment center in the west coast of Turkey. Materials and Methods: The survival rates of breast cancer patients (n = 1746) who have been treated from 1995 until 2008 were analyzed. The clinical data include age, menopausal stage, oestrogen (ER) and progesterone (PR) receptor status, and C-erbB-2 status as well as histopathological evaluation. AJCC (2002) was used for clinical tumor staging. Survival rates were computed using standard Kaplan-Meier methods, and the difference in survival curves was analyzed with the log-rank test. Results: The 14-year overall survival, disease-free survival, local failure-free survival, and distant failure-free survival rates were 77%, 95%, 77%, and 94%, respectively. Early-stage patients had higher overall survival rates compared to advanced-stage patients (stage IIIb and IIIc, AJCC 2002), and early-stage patients had higher survival rates than advanced-stage patients for disease-free survival, local failure-free survival, and distant failure-free survival. The risk for cancer development increases significantly for advanced-stage patients with positive ER and PR receptor as well as C-erbB-2 receptor. Conclusions: The incidence of breast cancer in Turkey is smaller compared to other European countries. Low advanced-stage patient numbers compared to high early-stage patient numbers; and very high median survival times could possibly be the result of the improvement of detection and treatment of breast cancer over the years.

Causas de óbito dos pacientes com câncer de mama diagnosticados e tratados no Hospital Erasto Gaertner de 1995 a 1999: estudo retrospectivo / Causes of death of the patients with breast cancer diagnosed and treated at the Erasto Gaertner Hospital from 1995 to 1999: retrospective study

Introdução: O câncer de mama é a segunda neoplasia mais frequente no mundo e é a principal causa de óbito entre as mulheres. Com o aumento do diagnóstico precoce, espera-se que outras causas, que não a neoplasia mamária, sejam determinantes à morte do paciente. O estudo objetivou verificar as causas de óbito das pacientes com câncer de mama tratadas no Hospital Erasta Gaertner, correlacionando os fatores de risco - estadiamento, idade, hipertensão arterial sistêmica e diabetes mellitus - com as principais causas. Metodologia: Foi realizado estudo retrospectivo através da revisão de prontuários das pacientes diagnosticadas entre 1995 e 1999; tratadas na instituição e que foram a óbito até setembro de 2008. Foram coletados dados referentes à idade da paciente no momento do diagnóstico, estadiamento, presença de comorbidades e causa da morte. Resultados: Faleceram 393 pacientes, com idade média ao diagnóstico de 53,8 anos. Em 30% dos casos, a causa de óbito não foi definida. Entre as causas de óbito conhecidas, progressão da doença à distância foi responsável por 87% dos óbitos, seguida de doenças do aparelho circulatório (6%) e outras neoplasias (2,5%). Conclusão: A principal causa de mortalidade averiguada foi progressão da doença à distância, principalmente nas pacientes com estádios avançados. Nas pacientes diagnosticadas precocemente, foi significativa a ocorrência de óbito por doenças do aparelho circulatório. A presença de HAS, DM e idade superior a 60 anos, mostraram-se como fatores de risco para óbito por outras causas, que não a neoplasia da mama.

Introduction: Breast cancer is the second most frequent neoplasm and the main cause of women's death. It is expected that with the increase in early diagnosis other reasons than breast cancer will determine the patient's death. The objective of this study was to verify the causes of death of patients treated for breast cancer at Erasto Gaertner Hospital, and related the risk factors such as; staging, age, Diabetes Mellitus (DM), and Arterial Hypertension to the main causes of the deaths found. Methods: A retrospective study was conducted through the review of medical records of patients diagnosed between 1995 and 1999, who received treatment at our Institution and died before September 2008. Data related to the patient was collected- patient's age at diagnosis, staging, the existence of comorbidities and cause of death. Results: 393 patients died, the mean age at diagnosis was 53.8 years. In 30% of the cases the cause of death was not defined. Among the causes of death, disease progression at distant sites was responsible for 87% of deaths, followed by cardiovascular diseases (6%) and by other kinds of neoplasm (2.5%). Conclusion: The main cause of mortality observed was the progression of the disease at distance, especially in patients in advanced stages. It was observed on patients who were early diagnosed a significant number of deaths from cardiovascular diseases. The presence of hypertension, DM and age higher than 60 years were considered risk factors for other causes of death apart from breast cancer.

Carcinoma de Mama Bilateral / Bilateral breast cancer

Introducción: La mayor incidencia del cáncer de mama, la mejora en los métodos de diagnóstico y tratamiento, junto al aumento en la expectativa de vida, llevan al incremento en el número de pacientes con riesgo de padecer un carcinoma de mama bilateral. La influencia en la sobrevida de estas pacientes es objeto de discusión. Objetivo: El objetivo del presente trabajo es describir las características de las pacientes con carcinoma de mama bilateral operadas en el Servicio de Patología Mamaria del Hospital Británico de Buenos Aires, y analizar el impacto en la sobrevida. Material y métodos: En el Servicio de Patología Mamaria del Hospital Británico de Buenos Aires, entre enero de 1970 y mayo de 2007, fueron tratados 4.085 casos de carcinoma mamario en 3.864 pacientes. Se realizó un estudio retrospectivo de 194 pacientes con carcinoma mamario bilateral: 80 sincrónicos y 114 metacrónicos. Para comparar el impacto en la sobrevida se utilizó un grupo de 2.237 pacientes operadas en el mismo período con carcinoma de mama unilateral. Definimos al carcinoma de mama bilateral sincrónico, como aquel que se presentó en forma simultánea en ambas mamas o hasta doce meses luego del primer diagnóstico. El carcinoma metacrónico se diagnosticó en la mama contralateral luego de doce meses con respecto al primero. Resultados: En nuestra serie, el riesgo de desarrollar un carcinoma en la mama contralateral fue aproximadamente del 0,9% anual, con un riesgo acumulado a 15 años del 12,75%. La probabilidad de sobrevida a 5 años fue 85,9% para los carcinomas unilaterales, 94,6% para los metacrónicos y 63,3% para los sincrónicos. A 15 años fue 65,5% para los unilaterales; 52,3% para los metacrónicos y 37,2% para los sincrónicos. Conclusiones: Los carcinomas bilaterales presentan una baja incidencia. El riesgo de desarrollar un carcinoma en la mama contralateral es del 0,9% anual.

Carcinomas mamários de tipo basal: perfil clínico-patológico e evolutivo / Basal-like breast cancers: clinicopathological features and outcome

OBJETIVO: Investigar a frequência de carcinomas mamários de fenótipo basal em uma série de tumores triplo-negativos (TTN), definidos pela negatividade para receptores de estrógeno (RE), de progesterona (RP) e HER2. MÉTODOS: Selecionamos 140 TTN, obtendo-se características clínico-patológicas e sobrevida. Microarranjo de tecido (2 cilindros de cada tumor) foi construído e submetido à imunoistoquímica para RE, RP, HER2, citoqueratinas (Cks) 5 e 14, EGFR, p63 e p53. Consideramos carcinomas de fenótipo basal os tumores negativos para RE, RP e HER2, e positivos para CK5. RESULTADOS: Encontramos 105 carcinomas de fenótipo basal entre 140 TTN (frequência=75 por cento). A idade média das pacientes foi de 54,8 anos, sendo que 34,3 por cento estavam na pré-menopausa. A maioria dos tumores foi classificada como carcinoma ductal invasor de alto grau. Os TTN exibiram positividade para CK5 (75,0 por cento), CK14 (29 por cento), EGFR (36,4 por cento), p63 (28,6 por cento) e p53 (67,1 por cento). Estadiamento avançado da doença foi observado em 52 pacientes (50 por cento), com diâmetro tumoral maior que 5 cm em 41 casos (39 por cento) e metástases axilares em 61 casos (59,2 por cento). Seguimento clínico foi obtido em 89 pacientes (média=51 meses). Destas, 45 pacientes (50,5 por cento) evoluíram sem doença; 6 (6,7 por cento) estavam vivas com doença e 38 (42,6 por cento) morreram pelo câncer. Recidiva sistêmica ocorreu em 42 pacientes (47,1 por cento), sendo pulmões, cérebro e ossos os principais sítios de metástases. As médias das sobrevidas global e livre de doença foram de 36 e 28 meses, respectivamente. CONCLUSÕES: Nosso estudo confirma comportamento clínico agressivo e elevada frequência dos carcinomas de fenótipo basal entre os TTN, semelhante ao descrito em casuísticas norte-americanas e europeias.

OBJECTIVE: The aim of our study was to investigate basal phenotype in a series of triple-negative (estrogen and progesterone receptors-negative and HER2-negative) invasive mammary carcinomas. METHODS: We selected 140 previously tested triple-negative tumors. Clinical, histopathological and survival data were obtained. A tissue microarray containing 2 cylinders from each tumor was constructed and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratins (CK) 5 and 14, EGFR, p63, and p53 was performed. We considered basal like-cancers (BLC) those tumors that were ER/PR/HER2-negative and CK5-positive. RESULTS: We found 105 cases of BLC from 140 triple-negative tumors (frequency=75.0 percent). The mean age at diagnosis was 54.8 years-old and 34.3 percent were premenopausal women. The majority of tumors were high grade (83.7 percent) and of ductal/no-special-type (80.8 percent). Triple-negative tumors showed immunoreactivity for CK5 (75.0 percent), CK14 (29.0 percent), EGFR (28.6 percent), p63 (28.6 percent), and p53 (67.1 percent). Tumor size larger than 5cm was observed in 41 cases (39.0 percent) and axillary metastases were detected in 61 patients (59.2 percent). Follow-up was recorded for 89 patients (mean=51 months): 45 patients (50.5 percent) with no evidence of disease; 6 patients (6.7 percent) were alive with disease; and 38 patients (42.6 percent) died of the disease. Relapse was detected in 42 women (47.1 percent), lungs, brain, and bones being the most common sites of metastasis. The mean overall survival was 36 months and the mean disease-free interval was 28 months. CONCLUSION: Our findings confirmed that BLC are poor prognosis and highly-frequent carcinomas among triple-negative tumors, similar to data previously reported in North American and European patients.

Factores pronósticos del carcinoma ductal in situ de mama / Prognostic factors in ductal carcinoma in situ of the breast

Objetivo: El objetivo primario del estudio es evaluar el impacto del índice pronóstico de Van Nuys (VNPI) en la recurrencia del carcinoma ductal in situ de mama (CDIS). Entre los objetivos secundarios se incluye la valoración de otros parámetros histológicos: el tamaño, el grado nuclear, la necrosis, la supervivencia libre de enfermedad y la supervivencia global. Método: Se analizaron los casos con diagnóstico de CDIS entre enero de 1995 a diciembre de 2000, de la base de datos de la Unidad de Mama del Hospital Universitario La Paz, Madrid, España. Se han recogido los hallazgos mamográficos, histológicos, así como la evolución de las pacientes. Resultados: Se diagnosticaron 95 CDIS en el periodo estudiado, de los que solo se incluyeron 79 casos en el análisis estadístico. El CDIS representa el 7,1 por ciento de todos los cánceres de mama en nuestro centro. La presencia de microcalcificaciones en la mamografía de cribado es el hallazgo diagnóstico mas frecuente. Ninguna de las variables clínicas analizadas se asoció a una mayor tasa de recaídas. Se asoció significativamente (p<0,05) a una mayor tasa de recurrencias el tamaño tumoral, el alto grado y la necrosis, así como el VNPI. Conclusiones: El CDIS tiene un comportamiento muy variable y ha de considerarse como entidades aisladas más que como una única enfermedad. Los parámetros biológicos e histológicos, principalmente el VNPI, podrían ayudara individualizar el tratamiento.

Objective: The primary endpoint of our study was to evaluate the impact of Van Nuys Prognostic index (VNPI) on recurrence of the breast ductal carcinoma in situ (DCIS). Secondary endpoints included other histologic features: size, nuclear grade, necrosis and architectural pattern, disease-free survival and ove-rail survival. Methods: Database of the breast unit was searched for patients with DCIS diagnose between January 1995 and December 2000. Clinical data, mammographic findings, pathological features, outcome and prognosis were studied. Results: Ninty five DCIS were detected at our center between 1995-2000, but only 79 patients were included in the statistical analysis. The incidence was 7.1 percent over the total number of breast cancers. Diagnose was made by a screening mammography in the majority of cases, and presence of microcalcifications was the most frequent mammographic finding. None of the clinical variables was associated to bigger rates of relapse. Tumour size, high grade and necrosis and VNPI had a significant association with recurrence. Conclusions: Disease outcomes are very diverse, and it is necessary to consider DCIS as different entities, more than as an isolated disease. Biologic and histological factors, mainly VNPI, allow to stratify patients according to their risk and help to individualize treatment.

Clinicopathological Characteristics of Male Breast Cancer

PURPOSE: To investigate clinicopathological characteristics and outcomes of male breast cancer (MBC). PATIENTS AND METHODS: We retrospectively analyzed the data of 20 MBC patients in comparison with female ductal carcinoma treated at Yonsei University Severance Hospital from July 1985 to May 2007. Clinicopathological features, treatment patterns, and survival were investigated. RESULTS: MBC consists of 0.38% of all breast cancers. The median age was 56 years. The median symptom duration was 10 months. The median tumor size was 1.7cm, 27.8% showed node metastasis, and 71.4% were estrogen receptor positive. All 20 cancers were arisen from ductal cells. No lobular carcinoma was found. The incidence of stages 0, I, II, and III in patients were 2, 10, 4, and 3, respectively. All patients underwent mastectomy. One with invasive cancer did not receive axillary node dissection and stage was not exactly evaluated. Adjuvant treatments were determined by pathologic parameters and stage. Clinicopathological parameters and survival rates of MBC were comparable to those of female ductal carcinoma. CONCLUSION: The onset age of MBC was 10 years older and symptom duration was longer than in female patients. No difference in outcomes between MBC and female ductal carcinoma suggests that the biology of MBC is not different from that of females. Therefore, education, an appropriate system for early detection, and adequate treatment are necessary for improving outcomes.

Cáncer de mama y prótesis / Prosthesis and breast cancer

La frecuencia de mujeres con implantes mamarios que desarrollarán cáncer aumentará considerablemente en los próximos años. Se comentan estudios epidemiológicos que relacionan riesgo de cáncer y prótesis. Se presentan 3 casos de pacientes con cáncer de mama e implantes, discutiéndose aspectos relacionados con el diagnóstico, tratamiento y resultados cosméticos de esta asociación aún poco frecuente.