Expression of aldehyde dehydrogenase after neoadjuvant chemotherapy is associated with expression of hypoxia-inducible factors 1 and 2 alpha and predicts prognosis in locally advanced breast cancer.

OBJECTIVE: To analyze the expression of hypoxia-inducible factors (hypoxia-inducible factor 1A and hypoxia-inducible factor 2A) and aldehyde dehydrogenase proteins in patients with locally advanced breast carcinoma who were subjected to neoadjuvant chemotherapy. METHODS: We included 90 patients with histologically confirmed stage II and III breast carcinoma who were treated with neoadjuvant chemotherapy between 2000 and 2005. Immunohistochemistry for aldehyde dehydrogenase, hypoxia-inducible factor 1A, and hypoxia-inducible factor 2A was performed before and after neoadjuvant chemotherapy. We analyzed the influence of clinical and pathological features on clinical and pathological response, disease-free survival, and overall survival. RESULTS: An objective clinical response to neoadjuvant chemotherapy was observed in 80% of patients, with 12% showing a complete pathological response. Among all clinical and pathological parameters, only the expression of hypoxia-inducible factor 1A was associated with a pathological response. A positive association was found between expression of aldehyde dehydrogenase and that of hypoxia-inducible factor 1A before and after chemotherapy. Aldehyde dehydrogenase expression was associated with expression of hypoxia inducible-factor 2A in tumors after neoadjuvant treatment. In a univariate analysis, prognosis was influenced by age, pathological response, metastasis to axillary lymph nodes after neoadjuvant chemotherapy, overexpression of hypoxia-inducible factor 2, and the presence of aldehyde dehydrogenase-positive cells within the primary tumor after neoadjuvant chemotherapy. In a multivariate analysis, only age and the presence of aldehyde dehydrogenase-positive cells after chemotherapy were associated with reduced overall survival. CONCLUSION: The presence of aldehyde dehydrogenase-positive cells within the residual tumor after neoadjuvant chemotherapy is associated with an increase in the expression of hypoxia-inducible factor 2A and with poor prognosis in patients with locally advanced breast cancer.

Expression of aldehyde dehydrogenase after neoadjuvant chemotherapy is associated with expression of hypoxia-inducible factors 1 and 2 alpha and predicts prognosis in locally advanced breast cancer

OBJECTIVE: To analyze the expression of hypoxia-inducible factors (hypoxia-inducible factor 1A and hypoxia-inducible factor 2A) and aldehyde dehydrogenase proteins in patients with locally advanced breast carcinoma who were subjected to neoadjuvant chemotherapy. METHODS: We included 90 patients with histologically confirmed stage II and III breast carcinoma who were treated with neoadjuvant chemotherapy between 2000 and 2005. Immunohistochemistry for aldehyde dehydrogenase, hypoxia-inducible factor 1A, and hypoxia-inducible factor 2A was performed before and after neoadjuvant chemotherapy. We analyzed the influence of clinical and pathological features on clinical and pathological response, disease-free survival, and overall survival. RESULTS: An objective clinical response to neoadjuvant chemotherapy was observed in 80% of patients, with 12% showing a complete pathological response. Among all clinical and pathological parameters, only the expression of hypoxia-inducible factor 1A was associated with a pathological response. A positive association was found between expression of aldehyde dehydrogenase and that of hypoxia-inducible factor 1A before and after chemotherapy. Aldehyde dehydrogenase expression was associated with expression of hypoxia inducible-factor 2A in tumors after neoadjuvant treatment. In a univariate analysis, prognosis was influenced by age, pathological response, metastasis to axillary lymph nodes after neoadjuvant chemotherapy, overexpression of hypoxia-inducible factor 2, and the presence of aldehyde dehydrogenase-positive cells within the primary tumor after neoadjuvant chemotherapy. In a multivariate analysis, only age and the presence of aldehyde dehydrogenase-positive cells after chemotherapy were associated with reduced overall survival. CONCLUSION: The presence of aldehyde dehydrogenase-positive cells within the residual tumor after neoadjuvant chemotherapy is associated with an increase in the expression ...

Idade como fator independente de prognóstico no câncer de mama / Age as an independent prognostic factor in breast cancer

OBJETIVO: comparar as características epidemiológicas e clínicas e a evolução pós-tratamento de mulheres com câncer de mama diagnosticadas antes ou após os 40 anos de idade. MÉTODOS: foi realizado um estudo retrospectivo, tipo caso-controle, com análise de informações obtidas dos prontuários de pacientes atendidas entre janeiro de 1994 e junho de 2004. Excluímos os casos com carcinomas intraductais e no estádio IV. Foram formados três grupos: pacientes com menos de 40 anos no diagnóstico (n=72), pacientes entre 40 e 50 anos (n=68) e pacientes com mais de 50 anos (n=75). Foram coletadas e analisadas informações sobre a idade no momento do diagnóstico, maior diâmetro das lesões, estadiamento clínico, tipo, grau histológico, presença de receptores hormonais e o estado dos linfonodos. O teste do chi2 foi empregado para variáveis qualitativas. Para as variáveis quantitativas que não apresentam distribuição normal (como número de gânglios axilares acometidos por metástases e tempo de seguimento), foi utilizado o teste de Kruskal-Wallis. Para a construção das curvas de sobrevida livre de doença e sobrevida global, foi utilizado o teste log-rank. RESULTADOS: não houve diferença na distribuição por estádios, no grau de diferenciação tumoral ou na distribuição dos tipos histológicos, na expressão de receptores de estrogênio ou c-erb-B2 entre os grupos. Encontramos diferença na expressão de receptores de estrogênio, que foi menos freqüente no grupo com menos de 40 anos em relação ao grupo com mais de 50 anos (36,2 versus 58,4 por cento). Não houve diferença nos diâmetros tumorais, que foram em média de 5,1, 4,7 e 5 cm. Não encontramos diferença nas taxas de acometimento de linfonodos axilares, que foram de 63,9, 46,9 e 50 por cento, respectivamente nas pacientes com menos de 40 anos, pacientes entre 40 e 50 anos e pacientes com mais de 50 anos. A média de seguimento foi de 54 meses nos três grupos. Houve recidiva da doença em 22,6 por cento das...

PURPOSE: to compare the epidemiologic and clinical characteristics, and the follow-up of breast cancer in women diagnosed under and over 40 years of age. METHODS: a retrospective study, case-control type, with analysis of information obtained from medical records of patients attended from January 1994 to June 2004. Cases of intraductal carcinoma and at stage IV were excluded. Three groups were formed: patients under 40 years old at the diagnosis (n=72); patients between 40 and 50 (n=68) and patients over 50 (n=75). Data about age at the moment of diagnosis, lesion largest diameter, clinical stage, type, histological grade, presence of hormonal receptors and state of the lymph nodes were collected and analyzed. The chi2 test was used for qualitative variables. For quantitative variables without normal distribution (such as number of axillary nodes with metastasis and follow-up duration), the Kruskal-Wallis' test was used. For delineating the curves of free-of-disease and global survival, the log-rank test was used. RESULTS: there was no difference among the groups in the stage distribution, concerning the tumoral differentiation grade or in the distribution of histological types, and in the estrogen receptor and c-erb-B2 expression. Difference was found in the RP expression, which was less frequent in the group of patients under 40, than in the group of patients over 50 (36.2 percent versus 58.4 percent) respectively. There was no difference among the groups in the mean tumoral diameter (5.1, 4.7 and 5 cm, respectively). There was also no difference among the groups, concerning the rate of axillary lymph node metastasis (63.9, 46.9 and 50 percent, respectively). The average follow-up was 54 months for all the groups. Disease recurrence occurred in 22.6 percent of patients under 40 years old, in 60 percent of patients between 40 and 50, and in 22.6 percent of patients over 50, with a significant difference among groups (p<0.0001). Death...

Treatment for low-risk gestational trophoblastic disease: comparison of single-agent methotrexate, dactinomycin and combination regimens.

OBJECTIVES: To compare the efficacy of three different standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the FIGO staging system in a single-institute setting. METHODS: From 1980 until 2002, we retrospectively reviewed 108 cases with low-risk persistent gestational trophoblastic disease who were treated with first-line chemotherapy. Patients were divided in three groups according to chemotherapy regimen: patients treated with methotrexate (MTX group; n=42), patients treated with dactinomycin (ACT group; n=42) and patients treated with methotrexate and dactinomycin in combination (MACT group; n=24). We compared the number of chemotherapy courses for achieving remission, the duration of treatment, the adverse side effects, the efficacy of the treatment and the need for performing a hysterectomy among the groups RESULTS: The complete remission rates were 69%, 61.4% and 79.1% for methotrexate (MTX), dactinomycin (ACT) and the combination regimen (MACT) treated groups, respectively (p=0.7). The duration of the treatment and the number of chemotherapy courses were similar among the groups (p=0.2 and p=0.4, respectively). Adverse side effects rate was reported to be 62.5% in the MACT group, 28.6% in the MTX group and 19.1% in the ACT group (p=0.0003). Second-line chemotherapy was indicated for 30 patients. Hysterectomy was performed in 21 patients overall, and there was no difference among the groups (p=0.6). CONCLUSION: Our analysis indicates that single-agent chemotherapy regimens are as effective as combination chemotherapy for low-risk gestational trophoblastic disease. Dactinomycin is a less toxic drug and might offer the best cost-effective treatment option. Methotrexate must be considered as the regimen of choice for low resource areas because of the feasibility of its administration.

[Age as an independent prognostic factor in breast cancer]. / Idade como fator independente de prognóstico no câncer de mama.

PURPOSE: to compare the epidemiologic and clinical characteristics, and the follow-up of breast cancer in women diagnosed under and over 40 years of age. METHODS: a retrospective study, case-control type, with analysis of information obtained from medical records of patients attended from January 1994 to June 2004. Cases of intraductal carcinoma and at stage IV were excluded. Three groups were formed: patients under 40 years old at the diagnosis (n=72); patients between 40 and 50 (n=68) and patients over 50 (n=75). Data about age at the moment of diagnosis, lesion largest diameter, clinical stage, type, histological grade, presence of hormonal receptors and state of the lymph nodes were collected and analyzed. The chi2 test was used for qualitative variables. For quantitative variables without normal distribution (such as number of axillary nodes with metastasis and follow-up duration), the Kruskal-Wallis' test was used. For delineating the curves of free-of-disease and global survival, the log-rank test was used. RESULTS: there was no difference among the groups in the stage distribution, concerning the tumoral differentiation grade or in the distribution of histological types, and in the estrogen receptor and c-erb-B2 expression. Difference was found in the RP expression, which was less frequent in the group of patients under 40, than in the group of patients over 50 (36.2% versus 58.4%) respectively. There was no difference among the groups in the mean tumoral diameter (5.1, 4.7 and 5 cm, respectively). There was also no difference among the groups, concerning the rate of axillary lymph node metastasis (63.9, 46.9 and 50%, respectively). The average follow-up was 54 months for all the groups. Disease recurrence occurred in 22.6% of patients under 40 years old, in 60% of patients between 40 and 50, and in 22.6% of patients over 50, with a significant difference among groups (p<0.0001). Death caused by the disease was higher among patients under 40 (46.9%) than among patients between 40 and 50 (26.9%) and over 50 (22.6%), p=0.0019. The logistic analysis showed that 'age under 40' and the 'presence of more than one metastatic axillary node' were independent death risk factors. CONCLUSIONS: age under 40 is an independent risk factor for breast cancer. The traditional prognostic indicators, such as stage, tumoral diameter, axillary involvement and presence of hormonal receptors are not associated with the disease evolution.