Fábio Eduardo Zola

HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

BackgroundNeoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting.MethodsSixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis.ResultsPreoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis.ConclusionImmunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination.

Breast conserving surgery after neoadjuvant therapy for large primary breast cancer

AIM The aim of this study was to evaluate the safety of breast conserving surgery in patients with breast tumours satisfactorily downstaged after neoadjuvant therapy. METHODS A retrospective cohort study was undertaken to analyze the loco-regional recurrence (LRR) after breast conserving surgery. We enrolled 88 patients with breast cancer subjected to neoadjuvant therapy (NAT group) who achieved an objective response due to neoadjuvant treatment and compared them with 191 patients with early breast cancer (EBC group) who were submitted to primary conserving surgery. Lumpectomy or quadrantectomy with axillary lymph node dissection was performed in all patients who received adjuvant radiotherapy. Systemic adjuvant therapy was offered to all patients. The mean periods of observation were 61.3 months in the NAT group and 67.5 months in the EBC group. RESULTS The mean age was 53 years in the NAT group and 56 years in the EBC group (p=0.04). There was no histological type and histological grade difference between groups. In the NAT group, the mean diameter of residual tumour was lower and the mean volume of breast tissue resection was higher than in the EBC group (p=0.01 and p=0.002, respectively). The ipsilateral recurrence rate was 7.9% in the NAT group and 7.8% in the EBC group (p=0.9). The most important predictive factor of recurrence in the NAT group was the age of patient. CONCLUSION Breast conserving therapy is a safe procedure in satisfactorily downstaged breast cancer after neoadjuvant therapy.

Impact of surgical staging in locally advanced cervical cancer and subsequent chemotherapy.

Surgical staging (SS) is the gold standard for determination of the true extent of a patients disease and is an important prognostic factor in cervical cancer. We investigated whether lymph node dissection (LND) prior to chemotherapy (CT) followed by radical surgery (RS) could modified overall (OS) and disease‐free survival (DFS).

Impacto prognóstico da recorrência local em pacientes com câncer inicial de mama submetidas a tratamento conservador

BACKGROUND: In order to investigate the impact of local recurrence on breast cancer patient prognosis, we developed this study. METHOD: A retrospective cohort study including 192 patients with early stage breast cancer subjected to breast conserving surgery (BCT) was performed to evaluate the local recurrence pattern and its role on disease progression. Using clinical and pathological criteria (time for recurrence, site of local recurrence and histological type) we classified patients as true local recurrence (TR group), new primary tumor (NP group), and patients free of local recurrence (FLR group). We compared the clinical course among these groups. RESULTS: Patients classified as NP are associated with young age and pre-menopausal status. The presence of TR is the most important predictive factor of prognosis and 40% of patients presented synchronic metastatic disease. The metastatic disease occurred in 28.5% and 4.7% of patients in the NP and FLR groups, respectively (p< 0.0001). Five-year overall survival rate was 75% in the TR group, 100% in the NP group and 98.2% in the FLR group (p< 0.0001). The Histological type and grade, margins status, lymph node metastasis and hormonal receptors were not predictive factors of local recurrence. Patients who were not submitted to hormonal therapy and young age are the most important predictive factors of local recurrence. CONCLUSION: True local recurrence had an influence on overall survival in patients with early breast cancer and the main risk factor for local recurrence was young age. The high-risk incidence for recurrence after BCT in such patients is a limiting factor of therapy.

Tumor neuroendócrino primário de mama: relato de três casos e revisão de literatura

Os tumores neuroendocrinos primarios de mama (TNPMs) sao incomuns e nao ha consenso quanto a tratamento e prognostico. No presente trabalho, foram revisados os diagnosticos de 1.184 pacientes com câncer de mama atendidos no Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP/USP), identificando tres casos que preenchiam os criterios de TNPM, segundo classificacao estabelecida pela Organizacao Mundial da Saude (OMS) em 2003. Foram avaliados os achados clinicopatologicos e imuno-histoquimicos e as terapias realizadas, buscando caracterizar os padroes histopatologicos e de comportamento distintos dos carcinomas convencionais de mama.

Breast Conserving Treatment in Early Breast Cancer: Impact of Local Recurrence Pattern on Patient Survival

To the Editor: Breast conserving therapy (BCT) has been considered the current standard care for early breast cancer treatment (1,2). With the widely used conservative surgery for breast cancer, an increasing number of local regional recurrence (LRR) has been diagnosed. The clinical course after local recurrence varies greatly. A considerable number of patients can be treated with savage mastectomy (3). However, some studies have shown that breast tumor recurrence is a predictor of distant metastases implying poor prognosis (4,5). To investigate the impact of local recurrence on patient prognosis, we developed this study. A retrospective study including 192 patients with early stage breast cancer subjected to BCT was performed to evaluate the local recurrence pattern and its role in disease progression. According to clinical and pathological criteria (time to recurrence, site of local recurrence, and histological type), we classified patients as true local recurrence (TR group), new primary tumor (NP group), and patients free of local recurrence (FLR group). Comparing the clinical course among these groups, we observed that patients classified as NP are associated with young age and premenopausal status and the presence of TR is the most important predictive factor of prognosis. Synchronic metastatic disease was observed in 40% of patients in TR group. On the other hand, the metastatic disease occurred in 28.5% and 4.7% of patients in the NP and FLR groups, respectively (p < 0.0001). The mean survival time was 43.7 months in the TR group, 112.6 months in the NP group and 105.9 months in the FLR group (p < 0.0001). Histological type and grade, margins status, lymph node metastasis and hormonal receptors were not predictive factors of local recurrence. Patients who did not undergo hormonal therapy and of young age are the most important predictive factors of local recurrence. We could not observe a relationship between inappropriate clear margin resection and the local recurrence. True local recurrence had an influence on overall survival in patients with early breast cancer treated with breast conserving surgery and the main risk factors for local recurrence were young age. According to our data, we assumed that, in patients who experience local recurrence, the definition between a new primary and a true recurrence using clinical and pathological criteria plays a crucial role in salvage therapy.

Estadiamento cirúrgico do câncer de colo de útero localmente avançado

PURPOSE: to assess to what extent the surgical staging differs from the clinical staging among cases of advanced uterine cervix carcinoma, and also to assess the percentage of cases with positive para-aortic ganglia in this group of patients. METHODS: this is a descriptive prospective study in which 36 patients with histological diagnosis of uterine cervix carcinoma considered locally advanced were included (stages IB2, IIB, IIIA and B, and IVA). The cases were submitted to clinical staging, according to FIGO criteria. All patients were to be treated with neoadjuvant chemotherapy. Age ranged from 40 to 73 years, with a mean of 56.2±7.9. The procedure started with pelvic lymphadenectomy followed by para-aortic lymphadenectomy, in case the pelvic lymph nodes were positive on surgical examination. Examination of the abdominal cavity and lymphadenectomy were done either through laparotomy or laparoscopy, chosen at random. In each case, the clinical staging was compared to the surgical staging, considered the gold standard. RESULTS: in the clinical staging (CS), 7 cases were classified as IB2 (tumors larger than 4 cm), 22 cases as CSII and 7 cases as CSIII. The surgical assessment changed the clinical staging as follows: the stage was decreased in six cases, and increased in 13. There was agreement only in 18 cases (50%). The para-aortic lymph nodes were affected in six cases. CONCLUSIONS: clinical staging of locally advanced uterine cervix carcinoma is incorrect in most of the cases. Such inconsistency may lead to excessive treatment in some cases, but about one fourth of the patients with positive para-aortic ganglia would not be adequately treated with the current standard treatment radiotherapy with chemosensitization, which aims at the local regional control of the pelvic disease.OBJETIVO: verificar em que proporcao o estadiamento cirurgico difere do estadiamento clinico entre casos com carcinoma avancado do colo do utero e a porcentagem de casos com gânglios para-aorticos positivos neste grupo de pacientes. METODOS: estudo prospectivo descritivo no qual foram incluidas 36 pacientes com diagnostico histologico de carcinoma de colo de utero considerados localmente avancados (estadios IB2, IIB, IIIAeB e IVA). Foram submetidas a estadiamento clinico conforme as recomendacoes da FIGO. Todas eram candidatas ao tratamento com quimioterapia neoadjuvante. A idade variou de 40 a 73 anos, com media de 56,2±7,9 anos. O procedimento constou de linfadenectomia pelvica seguida de linfadenectomia para-aortica se os linfonodos pelvicos fossem positivos ao exame intra-operatorio. A abordagem da cavidade e linfadenectomia foram efetuados por via laparotomica ou laparoscopica, indicados aleatoriamente. Os casos foram comparados individualmente e para cada estadiamento clinico foram estabelecidos os respectivos achados cirurgicos que foram considerados o padrao-ouro. RESULTADOS: na fase de estadiamento clinico (EC) 7 casos foram classificados como IB2 (tumores com mais de 4 cm), 22 casos como EC II e 7 casos ECIII. A avaliacao cirurgica modificou o estadiamento clinico da seguinte foram: em seis casos o estadio foi diminuido, e em 13 casos os achados levaram a elevacao do estadio. Houve concordância em apenas 18 casos (50%). Em seis casos (16,9%) os linfonodos para-aorticos estavam comprometidos. CONCLUSOES: o estadiamento clinico do carcinoma de colo de utero localmente avancado e incorreto em proporcao alta dos casos. Esta divergencia levaria a indicacao de tratamento excessivo em alguns casos, mas cerca de um quarto das pacientes com gânglios para-aorticos positivos nao seria adequadamente tratado com o tratamento padrao atual radioterapia com quimiossensibilizacao que e dirigida ao controle locorregional da doenca na pelve.