Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT).

BACKGROUND: Patients with breast cancer brain metastasis are a heterogeneous group in relation to tumor biology and outcome. MATERIALS AND METHODS: The group of 222 breast cancer patients with brain metastasis was divided into three biological subgroups. The propensity of biological subtypes for metastases to the brain and survivals depending on biological subtype, recursive partitioning analysis of Radiation Therapy Oncology Group (RPA RTOG) prognostic class and the use of systemic treatment after whole-brain radiotherapy were assessed. RESULTS: The rate of patients with triple-negative, human epidermal growth factor receptor 2 (HER2)-positive and luminal breast cancer with brain metastases was 28%, 53% and 19%, respectively. Median survival from brain metastases in triple-negative, HER2-positive and luminal subtype was 3.7, 9 and 15 months, respectively. Median survival from brain metastases in RPA RTOG prognostic class I, II and III was 15, 11 and 3 months, respectively. In the luminal and in the triple-negative subtype, systemic therapy prolonged survival from 3 to 14 months and from 3 to 4 months, respectively. In HER2-positive subtype, median survival without further treatment, after chemotherapy and after chemotherapy with targeted therapy were 3, 8 and 11 months, respectively. CONCLUSIONS: HER2-positive and triple-negative breast cancers have special predilection for metastases to the brain. Survival from brain metastases depended on performance status and the use of systemic treatment.

Immunohistochemical biomarkers in patients with early-onset breast carcinoma by tissue microarray.

UNLABELLED: Young women with breast cancer have a poor prognosis, and the role of biologic markers in young women is not well defined. We investigated the association of estrogen receptor, progesterone receptor, Bcl-2, HER-2/neu, p53, and Ki-67 with clinicopathologic features and outcome in young women with breast cancer. METHODS: A cohort of 103 patients with early-onset breast cancer treated with conservative surgery and radiotherapy were entered in this study. Age range was 25-45 years, and median follow-up was 8.7 years. Each of the paraffin-embedded specimens was immunologically stained for six biomarkers expression by a recently developed tissue microarray method. RESULTS: The 10-year overall breast relapse-free and distant relapse-free survival rates were 82.7%, 84.6.4%, and 66.7%, respectively, with 14 local relapses and 26 distant metastases among the 103 patients evaluated. Positive expression of estrogen receptor, progesterone receptor, bcl-2, HER-2/neu, p53, and Ki-67 were 42.7%, 48.5%, 35.6%, 28.0%, 36.9%, and 39.7%, respectively. Tumor stage and nodal status were significantly associated with overall survival and distant metastasis-free rate in univariate and multivariate analysis. Progesterone receptor negativity and Ki-67 positivity were associated with distant metastasis. There was no statistically significant correlation between the six biomarkers and local relapse. CONCLUSIONS: Progesterone receptor, Ki-67, tumor stage, and nodal status were prognostic factors for distant failure in early-stage breast cancer in young patients. Further studies are needed to find other biologic markers associated with local failure in this group of patients.

Identifying good prognosis group of breast cancer patients with 1-3 positive axillary nodes for adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy.

OBJECTIVE: We conducted a retrospective analysis of prognosis factors for survival in breast cancer patients with 1-3 axillary lymph node metastases and tried to identify a subset of patients with good prognosis suitable for cyclophosphamide, methotrexate and 5-fluorouracil (CMF) adjuvant chemotherapy. METHODS: A cohort of 446 breast cancer patients received definite surgery and adjuvant chemotherapy with CMF at Chang Gung Memorial Hospital from 1990 to 1998. They were enrolled in the study. The median follow-up time was 69 months. Prognostic factors including age, tumor size, number of involved nodes, steroid receptor status, tumor ploidy, synthetic-phase fraction, histologic grade and administration of tamoxifen were analysed for disease-free survival (DFS) and overall survival (OS) by Cox regression model. RESULTS: The estimated 5 year OS and DFS for all patients were 85.4 and 71.5%, respectively. Multivariate analysis revealed that tumor size, age and estrogen receptor (ER) status were independent prognostic factors for OS, and tumor size, age, ER status and number of involved nodes were independent prognostic factors for DFS. The 5 year OS rates of the low-risk group (age >40, tumor < or =3 cm and positive ER) and average-risk group (either age < or =40, tumor >3 cm or negative ER) were 98.8 and 82.4%, respectively (P = 0.0001). The 5 year DFS of the low-risk and high-risk group were 88.2 and 67.7%, respectively (P = 0.0001). CONCLUSION: Among breast cancer patients with 1-3 positive lymph nodes excellent survival rate was found in those who had favorable prognostic factors, including age >40, tumor size < or =3 cm and positive ER. Adjuvant chemotherapy with CMF regimen is optimal for these low-risk patients.

Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma.

BACKGROUND: The objective of this study was to assess hormone receptor status as an independent predictor of survival in a population-based cohort of women with breast carcinoma who were followed for up to 11 years. METHODS: Since 1990, the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program has collected data on hormone receptor status among patients with breast carcinoma. In a cohort of 205,736 women with breast carcinoma age > or = 20 years at diagnosis who were entered into the SEER data base between 1990 and 2000, the authors analyzed the association of hormone receptor status with year of diagnosis, patient age, disease stage, tumor histology, tumor grade, race/ethnicity, and metropolitan/statewide residence areas. Kaplan-Meier survival curves were compared according to hormone receptor status, and Cox proportional-hazards regression models were used to assess the association of hormone receptor status with breast carcinoma-specific and all-cause mortality controlling for age, disease stage, tumor grade, tumor histology, race/ethnicity, and SEER region. RESULTS: Women who had tumors that were positive for both estrogen and progesterone hormone receptors had significantly better survival than other women with breast carcinoma in the overall cohort, within each stage, and in the younger and older age groups, although the survival advantage was greater among women age < or = 50 years than among older women. Hormone receptor status was associated with mortality even when patient age, disease stage, tumor grade, tumor histology, race/ethnicity, and metropolitan/statewide residence areas were taken into account. CONCLUSIONS: Hormone receptor status was identified as an independent predictor of outcome in women with breast carcinoma. Data from clinical trials with long follow-up may shed light on whether and how the benefit of hormonal and other treatment varies with hormone receptor status.

Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival.

PURPOSE: The loss of Wnt-5a, a G-protein-coupled receptor ligand, or Syk, an intracellular kinase, has in separate studies been associated with poor prognosis of breast cancer patients. Both proteins are involved in cell adhesion, a key event in epithelial cancer metastasis. Here, we have investigated whether Syk is part of the Wnt-5a/discoidin domain receptor-1 (DDR1) signaling pathway and if a signaling interaction of these proteins is important for breast cancer-specific survival. EXPERIMENTAL DESIGN: The signaling interactions between Wnt-5a/DDR1 and Syk were addressed in mammary cell lines. Their mRNA and protein levels and the respective clinical correlates were investigated in 94 cases of primary breast cancer. RESULTS: The expression of Wnt-5a and Syk correlated in four of five tumor cell lines. However, despite a constitutive association between Syk and the Wnt-5a-dependent adhesion receptor DDR1, we found no evidence of a Wnt-5a/DDR1-mediated activation of Syk. Instead, beta(1) integrins initiate the adhesion-induced activation of Syk. In tumors from breast cancer patients, the protein expression of Wnt-5a and Syk were differently regulated at the translational and transcriptional level, respectively. Analysis of breast cancer-specific survival revealed that the presence of Wnt-5a and Syk in primary tumors has good predictive value for a favorable outcome. Intriguingly, a simultaneous loss of both proteins did not reduce survival more than loss of either. CONCLUSIONS: Despite the difference in regulation of Wnt-5a and Syk protein expression and their lack of signaling interaction, our clinical data indicate that a favorable prognosis in breast cancer requires the expression and signaling activity of both.

Racial/ethnic differences in survival rates in a population-based series of men with breast carcinoma.

BACKGROUND: A rare occurrence, about 1500 men in the United States develop breast carcinoma each year. Little is known about survival patterns at the population level, particularly about racial/ethnic variation. METHODS: Using data from the Surveillance, Epidemiology, and End Results Program, we examined survival rates in 1979 men diagnosed with primary invasive breast carcinoma between 1973 and 1997. Race was defined as non-Hispanic white, non-Hispanic black, and other race/ethnicity (predominantly Asian/Pacific Islander and Hispanic). The two outcomes were all-cause and breast carcinoma- specific mortality. Survival curves were drawn using Kaplan-Meier estimates and Cox regression was used to estimate the risk of death with hazard ratios and 95% confidence intervals. For both outcomes, the racial/ethnic survival curves differed significantly when the log rank test was used. Therefore, separate models were run for each racial/ethnic group. Covariates included age, stage, histology, surgery, radiation therapy, and year of diagnosis. Estrogen and progesterone receptor status were available for 616 men. RESULTS: Survival rates differed significantly by race/ethnicity. Overall, 5-year survival rates were 66% for whites, 57% for blacks, and 75% for men of other race/ethnicity. Blacks presented with more advanced disease. By stage, whites and blacks had worse survival rates compared with men of other race/ethnicity. The effects of prognostic factors such as age, surgery type, and radiation were similar, but not always significant, for all groups. Diagnosis year and estrogen receptor status did not affect survival. CONCLUSIONS: Survival following male breast carcinoma differed by race/ethnicity, whereas the prognostic factors associated with survival were similar.

Survival differences in breast cancer among racial/ethnic groups: a population-based study.

In women, breast cancer is the most frequent solid tumor and the second leading cause of cancer death. Differences in survival of breast cancer have been noted among racial/ethnic groups, but the reasons are unclear. This report presents the characteristics and the survival experience of four racial/ethnic groups and evaluates the effects of stage, age, histology, and treatment on survival time. The distributions of prognostic factors and treatment among racial/ethnic groups are compared using female breast cancer patients from two population-based registries in Southern California. The main end points are observed survival time and survival by cause of death. The Cox model is used to estimate the relative risk of death in three minority groups compared with non-Hispanic whites, while controlling for several covariates. Breast cancer cases included in this study were 10,937 non-Hispanic whites, 185 blacks, 875 Hispanics, and 412 Asians. The median follow-up period was 76 months (range: 48-132). The median age at diagnosis was 64 years among non-Hispanic whites, 55 years among Hispanics (p = 0.001), 52 years among blacks (p = 0.001), and 50 years among Asians (p = 0. 001). There was more localized disease among non-Hispanic whites (61. 4%) than among blacks (50.8%) and Hispanics (52.2%), but not compared to Asians (59.7%). After controlling for stage, age, histology, treatment, and registry, overall survival significantly differed between non-Hispanic whites and blacks [relative risk (RR) = 2.27, 95% confidence interval (95% CI) 1.82-2.84) and between non-Hispanic whites and Hispanics (RR = 1.18, 95% CI 1.04-1.34). The same results were found for breast cancer death in blacks (RR = 2.32, 95% CI 1.76-3.07) and Hispanics (RR = 1.28, 95% CI 1.10-1.50). We found no difference between Asians and non-Hispanic whites in overall and cancer-related survival. These results show that stage of disease, age at diagnosis, histologic features and treatment for breast cancer differed among racial/ethnic groups. Moreover, black women, in particular, and Hispanic women with breast cancer had a higher risk of death compared to non-Hispanic white women, even after controlling for prognostic factors. These findings underline the necessity of improved screening and access to appropriate treatment among minority women for breast cancer.

Cáncer de mama en mujeres mayores de 65 años / Breast cancer in 65 years older women

Antecedentes: La influencia de la edad sobre el pronóstico de los carcinomas mamarios es un tema controvertido y por ello el enfoque terapéutico es variado. Objetivo: Se analizan las características clínico-patológicas en una serie de 174 carcinomas de mamas en mujeres mayores de 65 años de edad. Resultados: Para ambos grupos los resultados no mostraron diferencias significativas en cuanto al tamaño de los tumores, la incidencia de ganglios metastásicos, los grados nuclear e histológicos ni en la expresión inmunohistoquímica de los receptores de estrógenos y progesterona, c-erbB-2, bcl-2, p53, MIB-1 y antígeno carcinoembriónico. En el seguimiento también mostraron similar tasa de recidiva local, de metástasis a distancia y de muerte por la enfermedad mientras que las muertes por otras causas fueron cuatro veces mayores en el grupo de más edad que en el grupo de pacientes más jóvenes. Conclusión: En esta serie la edad no fue un factor que permitiera establecer diferencias en las características biológicas analizadas ni en el comportamiento de las neoplasias. La mayor mortalidad por otras causas resulta lógica en el grupo de pacientes mayores. Este dato debería ser considerado al planear terapéuticas en pacientes de edad avanzada cuando las características de la enfermedad permiten prever una sobrevida mayor a la expectativa de vida esperada por la edad

Cáncer de mama en mujeres mayores de 65 años / Breast cancer in 65 years older women

Antecedentes: La influencia de la edad sobre el pronóstico de los carcinomas mamarios es un tema controvertido y por ello el enfoque terapéutico es variado. Objetivo: Se analizan las características clínico-patológicas en una serie de 174 carcinomas de mamas en mujeres mayores de 65 años de edad. Resultados: Para ambos grupos los resultados no mostraron diferencias significativas en cuanto al tamaño de los tumores, la incidencia de ganglios metastásicos, los grados nuclear e histológicos ni en la expresión inmunohistoquímica de los receptores de estrógenos y progesterona, c-erbB-2, bcl-2, p53, MIB-1 y antígeno carcinoembriónico. En el seguimiento también mostraron similar tasa de recidiva local, de metástasis a distancia y de muerte por la enfermedad mientras que las muertes por otras causas fueron cuatro veces mayores en el grupo de más edad que en el grupo de pacientes más jóvenes. Conclusión: En esta serie la edad no fue un factor que permitiera establecer diferencias en las características biológicas analizadas ni en el comportamiento de las neoplasias. La mayor mortalidad por otras causas resulta lógica en el grupo de pacientes mayores. Este dato debería ser considerado al planear terapéuticas en pacientes de edad avanzada cuando las características de la enfermedad permiten prever una sobrevida mayor a la expectativa de vida esperada por la edad (AU)