Long-term outcome of adjuvant chemotherapy cyclophosphamide, mitoxantrone, and fluorouracil in women with breast cancer.

The aim of the study is to report the long-term outcome and secondary tumours of early breast cancer patients of adjuvant CNF (cyclophosphamide, mitoxantrone, and 5-fluorouracil) chemotherapy. One hundred and ninety four patients, 185 primary early breast cancer and nine locoregionally recurrent breast cancer patients, were entered onto the trial between May 1986 and November 1993. The therapies included surgery, radiation therapy, adjuvant CNF chemotherapy, and tamoxifen according to hormonal status. Some of patients were treated twice with CMF (methotrexate). The median follow-up time was 12.9 years. Eighty nine (48%) primary breast cancers relapsed, and six locoregional breast cancers relapsed. After 5-10 years the relapse incidence decreased notably. Eighty three patients died of breast cancer, and nine of other causes. Two cases of leukemia, six cases of skin cancer, two cases of Hodgkin's disease, two cases of meningioma, and two cases of endometrial cancer were observed. This article confirms the feasibility of adjuvant CNF for early breast cancer patients. Questions of possible causability of secondary cancer have yet to be explored.

Inducible nitric oxide synthase expression in pharyngeal squamous cell carcinoma: relation to p53 expression, clinicopathological data, and survival.

OBJECTIVE: To investigate the expression of inducible nitric oxide synthase (iNOS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC) and its relation to p53 expression, histologic differentiation, clinical data, and prognosis. STUDY DESIGN: A retrospective survey. METHODS: Primary tumors for analyses were obtained from 118 patients diagnosed with SCC of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemical analysis was used to evaluate the expression of iNOS and p53. The expression pattern of iNOS was related to p53 expression, clinical data, and survival. RESULTS: High iNOS score was associated significantly with high nuclear p53 expression index (P = .006) and positive cytoplasmic p53 expression (P = .025). The score for iNOS expression was significantly lower in the largest (T4) tumors (P = .043). No association was seen between iNOS score and N or M class, tumor stage, or histologic differentiation. The score for iNOS expression was not related to overall survival. CONCLUSIONS: The expressions of iNOS and p53 seem to be inter-related in pharyngeal SCC, although the causality remains to be clarified. The expression of iNOS shows no prognostic value in pharyngeal SCC.

Nuclear and cytoplasmic p53 expression in pharyngeal squamous cell carcinoma: prognostic implications.

BACKGROUND: The role of p53 expression in human neoplasms is still controversial, and it has been associated with both favorable and unfavorable outcome of the patients. Also cytoplasmic expression of p53 protein has been reported to affect survival in some cancers. Furthermore, an association between p53 and beta-catenin expression has been demonstrated. We studied the expression of p53 in a large group of oropharyngeal and hypopharyngeal squamous cell carcinomas and its relation to catenin expression, histologic differentiation, clinical data, and prognosis. METHODS: Primary tumors for analyses were obtained from 123 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in Eastern Finland. Immunohistochemistry was used to evaluate the expression of p53 as well as alpha-, beta-, and gamma-catenins. RESULTS: In the primary tumors (n = 123), the nuclear p53 expression index was low in 42 (34%), intermediate in 38 (31%), and high in 43 (35%) cases. Cytoplasmic p53 expression was present in 56 (46%) and absent in 67 (54%) tumors. In univariate analyses (Kaplan-Meier), hypopharyngeal primary site (p =.02), high T class (p <.0005), presence of distant metastases (p =.02), low Karnofsky performance index (p <.0005), high nuclear p53 expression index (p =.01), and positive cytoplasmic p53 expression (p =.04) predicted poorer overall survival (OS). In Cox proportional hazards model, only T class (p =.0005), Karnofsky performance index (p =.005), and nuclear beta-catenin expression (p =.038) predicted poorer OS. CONCLUSION: Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate to more aggressive features and unfavorable outcome in pharyngeal squamous cell carcinoma (PSCC). However, unlike more traditional variables, p53 expression is not an independent predictor of disease outcome in PSCC.