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F Pozza

Publications and source records attributed to F Pozza.

At least 19 recordsLinked to original sources

Regulation of longevity and stress resistance by Sch9 in yeast.

The protein kinase Akt/protein kinase B (PKB) is implicated in insulin signaling in mammals and functions in a pathway that regulates longevity and stress resistance in Caenorhabditis elegans. We screened for long-lived mutants in nondividing yeast Saccharomyces cerevisiae and identified mutations in adenylate cyclase and SCH9, which is homologous to Akt/PKB, that increase resistance to oxidants and extend life-span by up to threefold. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 were required for this life-span extension. These results indicate that longevity is associated with increased investment in maintenance and show that highly conserved genes play similar roles in life-span regulation in S. cerevisiae and higher eukaryotes.

Adenylyl Cyclases↗

Linear accelerator radiosurgery of cerebral arteriovenous malformations: current status.

228 patients affected by cerebral arteriovenous malformations (AVMs) underwent linear accelerator radiosurgery. Follow-up ranges from 1 to 100 months (mean 42 months). Complete angiographic obliteration was achieved in 47% of treated patients at one year and 80% at 2 years. 17 haemorrhages were observed after treatment and 6 patients died from them. No bleeding took place after complete angiographic obliteration. 11 patients suffered for radionecrosis. In 6 patients complete recovery was obtained with corticoid medication. The aim of this study is to present our results and to evaluate the effect of irradiation on the risk of bleeding after radiosurgery. Patients were considered at risk in the time lapse after irradiation and before angiographic obliteration or other definitive treatment or death. Patients were followed from the date of radiosurgery and the number of haemorrhages were recorded every six months. In our series the bleeding risk in patients harbouring incompletely obliterated AVMs decreases from 8% in the first year after radiosurgery to 0% starting from the 24th month of the follow-up.

Adolescent↗

A multiparametric study on the prognostic value of epidermal growth factor receptor in operable breast carcinoma.

Epidermal growth factor receptor (EGFR) is a potentially useful new biological prognostic and predictive indicator in human breast cancer. Additional research on EGFR is warranted to enhance our information on: i) the method of choice for its detection and quality control issues; ii) its association with novel pathobiological markers of prognosis; iii) its prognostic value in multivariate analysis; and iv) its capability to predict response to hormone therapy and, in the future, to biological treatments using antibodies against the specific receptor or its ligands. In the present study we update previous data on EGFR status, determined immunocytochemically, by prolonging the period of observation up to 5 years and by including, in the multivariate analysis, several new biological indicators. The main results obtained are: i) EGFR is weakly associated with Ki-67 score (p = 0.073) and with p53 expression (p = 0.06); ii) EGFR is a significant indicator for recurrence (p < 0.01 and odds ratio of 2.82) but not for death (p = 0.27 and odds ratio of 1.49); iii) the prognostic power of EGFR is enhanced when combined with the knowledge of S-phase fraction; and iv) in multivariate analysis on relapse-free survival, EGFR and S-phase fraction (likelihood ratio test = 26.40; p < 0.01), c-erB-2 protein and p53 mutant protein expression (likelihood ratio test = 5.94; p = 0.05), cathepsin D (likelihood ratio test = 9.78; p < 0.01), and nodal status (likelihood ratio test = 7.32: p < 0.01) are significant and independent prognostic factors in early-stage breast carcinoma. This new information could be of help for a more rational approach in the use of EGFR as a marker in future clinical research.

Age Factors↗

c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma--an immunocytochemical study.

The type I growth factor receptor family has been found to play an important role in the control of normal growth and differentiation. Moreover, the epidermal growth factor receptor and the c-erbB-2 oncogene seem to be implicated in the pathogenesis and behaviour of several cancers, including breast cancer. c-erbB-3 is a new member of the type I receptor family for which there is currently little information available on its expression in neoplastic tissues, and on its possible prognostic significance. This study was undertaken to define the prognostic value of c-erbB-3 expression in a series of node-negative breast cancer (NNBC) patients when compared, by multivariate analysis, with expression of the c-erbB-2 protein and conventional clinicopathological features. cerbB-3 was recognised by the novel monoclonal antibody RTJ1, whereas c-erbB-2 was detected by the polyclonal antibody 21N, using immunocytochemical methods. We found that overexpression of c-erbB-3 occurs frequently in NNBC. Overall, 138 of 212 carcinomas (65%) had some degree of membrane RTJ1 staining, and 28 (13%) showed strong and generalised positivity ( ). Twenty-four per cent of carcinomas had membrane 21N staining, and 12% presented strong and generalised positivity ( ). c-erbB-3 protein expression was significantly associated only with that of c-erbB-2 (P = 0.05), whereas 21N positivity was significantly associated with small tumour size (P = 0.02) and ductal histotype (P = 0.04). No significant correlation between expression of either receptor proteins or relapse-free survival was observed after a median follow-up of 63 months. Applying multivariate analysis, only tumour size approached significance. Our results indicate that analysis of expression of c-erbB-3 and c-erbB-2 alone do not seem to be useful in identifying patients with NNBC at different risk of relapse or death.

Adult↗

Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma.

PURPOSE: To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS: We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS: Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION: MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.

Adult↗

Linear accelerator radiosurgery of cerebral arteriovenous malformations: an update.

One hundred eighty patients affected by cerebral arteriovenous malformations (AVMs) underwent radiosurgical treatment in our department. One hundred fifty-three patients have been treated with complete irradiation of the entire AVM nidus. In 27 patients (with large and/or three-dimensional irregular target volumes), only part of the nidus was covered with a dose adequate for obliteration. Follow-up ranged from 88 to 1 months (mean, 43.1 mo). Angiographic control was performed at 12, 24, and 36 months until complete obliteration was attained. The complete obliteration rate was 46% at 1 year and 80% at 2 years. We observed 15 hemorrhages after treatment, and five patients died from them. No bleeding took place after complete angiographic obliteration. The aim of this study is to evaluate the effect of irradiation on bleeding risk after radiosurgery and before complete obliteration. Inclusive parameters of patients considered at risk were as follows: 1) all patients in the time lapse between irradiation and demonstrated complete angiographic obliteration; 2) all patients in the time lapse between irradiation and definitive treatment either by surgery or embolization; and 3) all patients in the time lapse between irradiation and death. These groups include all irradiated patients who still had incompletely obliterated AVMs. They were stratified starting from 0 time (the date of radiosurgery), and the hemorrhages were evaluated every 6 months. In totally irradiated cases, the bleeding risk decreased from 4.8% in the first 6 months after radiosurgery to 0% starting from the 12th month of the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma.

Squamous-cell carcinoma of the head and neck includes a heterogeneous group of tumours of the upper air and food passages for which prognosis is difficult to assess. In fact, patients in comparable stages may have diverse clinical courses and responses to similar treatments. In order to better define the prognosis of each patient there is therefore a need to identify novel biological markers which reflect more accurately growth rate, progression and metastatic potential of each tumour. We assessed whether metastases correlate with microvessel counts (i.e. intratumoral vascularity) using the CD-31 monoclonal antibody (MAb) and p53 mutant protein expression, determined in the primary by immunocytochemical methods in 70 patients with locally advanced head and neck cancer. Patients were treated with concurrent chemo-radiotherapy; 50 of these presented loco-regional node metastasis at diagnosis whereas 3 cases, initially node-negative, developed distant metastasis during the period of observation. No feature was predictive for objective response to treatment. The overall mean and median blood vessel density at "hot spots" was 37.42 and 36, respectively, and 57% of the tumours expressed p53 mutant proteins. These 2 biological markers were significantly associated. Patients with metastases (loco-regional and distant) had a significantly higher mean blood-vessel density than those without tumour spread. Also, patients with p53-positive (+/++) tumours had a significantly higher incidence of metastasis than those with negative ones. Multivariate analysis showed that both vascularity and stage, but not p53 expression, are significant and independent predictors of metastasis in this series.

Adult↗

Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients.

The incidence of breast cancer is increasing in all Western countries. Due both to a more widespread public education and to early diagnosis by mammography screening programs, the percentage of patients with node-negative breast cancer has gone up to 70%. Thus, node-negative breast cancer is a major public health problem and, consequently, clinical research in this setting is an expanding field. A recent overview analysis confirmed the results of five prospective randomized clinical trials suggesting that systemic adjuvant therapy can benefit node-negative breast cancer patients. Because of the heterogeneity of node-negative breast cancer, it is reasonable to attempt to avoid excessive treatment morbidity and costs by using selective prognostic markers to identify patients at high risk for disease recurrence who are eligible for postsurgical systemic adjuvant therapy. It is also desirable to use predictive markers in selecting the therapy to which each patient is more likely to respond. The need for additional prognostic and predictive factors has led to identification of a plethora of potentially useful markers. As a result, the selection of patients at different risks of developing node-negative breast cancer and the choice for appropriate therapy remain difficult and confusing for the clinician. Moreover, the majority of studies have examined new markers individually rather than by multivariate analysis and retrospectively rather than prospectively. Thus, there are also important methodologic biases in such studies. This analysis consists of (a) defining the clinical "problem," (b) defining the terms of prognostic and predictive factors, (c) suggesting more appropriate laboratory and clinical approaches to properly evaluate a new indicator, (d) identifying the subsets of patients in whom the use of new prognosticators is warranted and of particular importance, and (e) providing some direction for future research on this topic. Our ultimate goals are to facilitate the understanding of node-negative breast cancer prognostic markers among clinicians, to help them select the most appropriate indicator for specific situations, and to recommend methodology for future research.

Adult↗

Analysis of dosimetric measurements in linac radiosurgery calibration.

The aim of this paper is to analyse the dosimetric parameters of a linear accelerator used in radiosurgery treatments. The influence of these parameters on the resulting dose distribution are basic for delivering the predefined dose to the vascular or oncological target volume. Several dosimetric methods have been used to define the output factors for small fields. The thimble and the Markus chambers, TLD and film dosimetry are investigated; all these dosimetric systems give reliable and almost similar results if used in the correct way. In the determination of tissue maximum ratio (TMR) the response curves obtained by ionometric and film dosimetry were investigated. For TMR determination the use of the Markus chamber and the correction factors to be applied as a result of the small dimension of the field were also investigated.

Calibration↗

From radiotherapy to stereotactic radiosurgery: physical and dosimetrical considerations.

The aim of this presentation is to analyse the mechanical and dosimetrical parameters of the linear accelerator used in stereotactic radiosurgery. The use of the thimble and Markus chambers, TL and film in small field dosimetry are investigated. To determine the optimal irradiation technique and dose distribution, the dose volume to healthy tissue is considered.

Humans↗

Surgical and adjuvant radiation therapy of resectable retroperitoneal soft tissue sarcomas in adults.

Primary soft tissue sarcoma of the retroperitoneum is a rare disease. A series of 11 evaluable adult patients with retroperitoneal soft tissue sarcomas is reported. These patients were treated with complete surgery and adjuvant radiation therapy (total dose from 50 to 64 Gy) using an 18 MeV linear accelerator. After a median follow-up of 48 months (range, 6-84), 4 patients had a local-regional recurrence, 3 had distant metastases, and 4 died of progressive disease. Four-year estimated disease-free survival was 54.5% and overall survival was 70%. Treatment was well tolerated by most patients: 7 patients experienced moderate gastrointestinal toxicity, mainly nausea and diarrhea, during radiotherapy; 2 cases had weight loss > 15% at the end of the therapy; and chronic ileitis was observed in 2 cases. We conclude that adjuvant radiotherapy seems to reduce the incidence of local-regional recurrences in these patients. No radiation-induced irreversible injury was observed, but one young woman had amenorrhea after radiotherapy. Controlled clinical trials are warranted to define the role and effectiveness of adjuvant radiotherapy and/or chemotherapy in retroperitoneal soft tissue sarcomas.

Adult↗

Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.

BACKGROUND: Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE: This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS: In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS: There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS: Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS: Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.

Adult↗

Progesterone receptor determined by immunocytochemical and biochemical methods in human breast cancer.

Immunocytochemical assay (ICA) of the progesterone receptor (PgR) was performed on 152 patients with stage I-II breast cancer. We employed the rat monoclonal antibody KD-68 and a peroxidase/antiperoxidase displaying system. The results obtained by ICA (Pg(RICA)) were compared with those by the biochemical dextran-coated charcoal assay (PgRDCC). Comparing the two methods we found an overall agreement (accuracy) of 77.5%, a PgR(ICA) sensitivity of 83.5% and a specificity of 73%. Both methods were significantly associated with oestrogen receptor expression, detected by DCC (P less than 0.001 for PgRDCC and P = 0.0014 for PgR(ICA)). No significant association was found between PgR(ICA) or PgRDCC and the other clinicopathological features analysed. After a median follow-up of 36 months, the overall survival probability was 91% in PgRDCC-positive versus 81.5% in PgRDCC-negative patients (log-rank test, chi 2 = 0.91) compared to 87.5% in PgR(ICA)-positive versus 82% in PgR(ICA)-negative ones (log-rank test, chi 2 = 0.93). Disease-free survival probability was 74.5% in both PgRDCC-positive and PgRDCC-negative patients (log-rank test, chi 2 = 0.02) compared to 78% in PgR(ICA)-positive versus 71.5% in PgR(ICA)-negative cases (log-rank test, chi 2 = 0.37). The present study demonstrates that ICA is a reliable method to detect PgR, correlating well with the DCC assay. Moreover, the ICA assay seems to provide clinical information complementary to the biochemical method. The definition of its prognostic value in operable breast cancer needs additional studies, particularly in node-negative patients.

Adult↗

Peritumoral lymphatic vessel invasion compared with DNA ploidy, proliferative activity, and other pathologic features as prognostic indicators in operable breast cancer.

In 164 breast carcinomas the presence of peritumoral lymphatic vessel invasion (PLVI) was evaluated and correlated with other known indicators of prognosis and with the clinical outcome of the patients. Overall 22% of tumors were PLVI-positive. The presence of PLVI was significantly associated with axillary node involvement (p less than 0.0001) and tumor size (p = 0.005), and tended toward an association with grading (p = 0.065). No significant association was found between PLVI and steroid hormone receptors, DNA ploidy, or proliferative activity. Univariate analysis shows that peritumoral vessel invasion was significantly associated with a higher risk of recurrence (p = 0.012) and with a trend toward shorter survival (p = 0.074). Besides the presence of PLVI, prognosis was significantly worse also for patients with high proliferative aneuploid tumors and with axillary node metastases. Moreover, within the subsets of patients generally considered to have good prognosis, the presence of PLVI identified patients with a trend for higher risk such as those with PLVI-positive diploid tumors, PLVI-positive low-proliferative tumors, and PLVI-positive node-negative tumors. Adopting multivariate analysis, PLVI failed to retain prognostic importance when adjusted for node status, DNA ploidy, and proliferative activity. In conclusion, we found that the presence of PLVI has prognostic significance when singly evaluated. Multivariate analysis shows that PLVI is not an independent prognostic factor in stage I-II breast cancer.

Adult↗

Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer.

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is important in the regulation of breast cancer cell growth. The relationship between EGFR status (determined by an immunocytochemical assay) and various prognostic factors was investigated in 164 primary breast cancers. Overall 56% of tumours were EGFR-positive and the expression of EGFR was unrelated to axillary node status, tumour size and histological grade; and it was poorly associated with the tumour proliferative activity measured by Ki-67 immuno-cytochemistry. The relapse-free survival (RFS) probability at 3-years was significantly worse for patients with EGFR positive tumours (P = 0.003) and for those whose Ki-67 score was > 7.5% (P = 0.0027), as well as in patients with axillary node involvement (P = 0.01) and with poorly differentiated tumours (P = 0.04). Immunocytochemical determination of EGFR and cell kinetics gave superimposable prognostic information for predicting RFS with odds ratios of 3.51, when evaluated singly. In our series of patients EGFR, Ki-67 and node status retain their prognostic value concerning RFS in multivariate analysis. The 3-year probability of overall survival (OS) was significantly better in node-negative patients (P = 0.04) and was similar in EGFR-positive and negative patients. In conclusion, EGFR status appears to be a significant and independent indicator of recurrence in human breast cancer and the concomitant measurement of the tumour proliferative activity seems to improve the selection of patients with different risks of recurrence.

Adult↗

Osteosarcoma of the facial bones.

Maxillo-facial osteosarcoma is a rare primary tumor in adults. Between 1980 and 1990, 11 patients were considered; 6 had primary tumors in mandible and 5 in the maxillo-paranasal region. All cases were treated with surgery as the primary modality. Resection was radical in 8 patients and palliative in the other 3. Adjuvant postoperative chemotherapy with adriamycin was administered for 6 months in the 8 patients treated with complete resection. After a median follow-up of 3 years, 7 patients are still alive and 4 died of progressive disease. In the group of patients treated with radical surgery and adjuvant chemotherapy only one died for distant metastases, and 7 are living free of disease. With complete surgical resection long term local tumor control was achieved in all patients. No patient treated with incomplete resection achieved local tumor control with subsequent radiotherapy. The possibility of performing a complete surgical resection of the primary appears to be an essential step to obtain long term local control and survival in maxillo-facial osteosarcoma. Our series is, however, too limited to evaluate the therapeutic benefit of adjuvant chemotherapy.

Adolescent↗

Synchronous radiotherapy and chemotherapy with cisplatin in the management of locally advanced or recurrent head and neck cancer.

A synergism between cisplatin and radiotherapy has been demonstrated in in vitro and in vivo studies. To improve the locoregional control of disease and the survival rate in patients affected by locally advanced or recurrent squamous cell carcinoma of the head and neck, we planned a Phase II study of concurrent radiotherapy, 2 Gy for 5 days every week for a total dose of 60-70 Gy with cisplatin 80 mg/m2 every 21 days for 2 or 3 doses (on days 1, 21, 42). Fifty-one patients were entered in the study; 48 were evaluable for response and toxicity; 18 (37.5%) had untreated Stage III disease; 25 (52%) had Stage IV disease; 5 (10.5%) had recurrent disease. The complete response rate in Stage III-IV patients was 63% (27 of 43) with 95% confidence limits from 48 to 77% (+/- 14.5%). In the group of five patients with recurrent disease, only one (20%) achieved a complete response. In patients with Stage III-IV disease, a significantly higher complete response rate was observed for those younger than 58.5 years (p = 0.05). The overall estimated 1- and 2-year survival was 59% and 37%, respectively, and a significantly better survival was observed in complete responders compared to partial responses or patients with stable disease (p = 0.037). Disease-free survival was 46% and 36% at 1 and 2 years, respectively. Distant failure occurred only in 12.5% of the patients. Overall, the treatment was well tolerated, and only three patients refused to complete the planned therapy. Gastrointestinal and hematological toxicity were the most common side effects. Data from present trial were compared with that of 50 patients with comparable characteristics treated with radiotherapy alone from 1985 to 1987 as a historical control. The complete response rate, the disease-free survival, and the overall survival appear to be better in the patients treated with chemoradiotherapy. It was concluded that the combination of chemoradiotherapy in patients with Stage III-IV head and neck squamous cell carcinoma is an effective and safe treatment with an apparent better locoregional control than radiotherapy alone. Survival results need to be evaluated in a Phase III randomized trial.

Adult↗

Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features.

PURPOSE: A study was undertaken to define the prognostic value of the expression of the c-erbB-2 oncoprotein in a series of breast cancer patients when compared by multivariate analysis with expression of the epidermal growth factor receptor (EGFR), DNA ploidy, and conventional clinicopathologic features. PATIENTS AND METHODS: Prognostic indicators were analyzed in 165 primary breast cancers. The c-erbB-2 oncoprotein was recognized by the polyclonal antibody 21N using an immunocytochemical method. Expression of the EGFR was stated immunocytochemically using the monoclonal antibody EGFR1. DNA ploidy was assessed in paraffin-embedded sections using a standard flow-cytometric method. RESULTS: Overall, 27% of carcinomas had membrane 21N-staining and were classified as c-erbB-2-positive. Overexpression of the c-erbB-2 oncoprotein was poorly associated with EGFR expression and the conventional pathologic features, and it was weakly associated with DNA ploidy and nodal status. Univariate analysis showed that c-erbB-2 expression, nodal status, DNA ploidy, and EGFR provided significant prognostic information concerning 4-year relapse-free survival (RFS) with the odds ratios (ORs) of not relapsing of 2.94, 2.83, 2.34, and 2.20, respectively. Regarding overall survival (OS) at 4 years, only nodal status and DNA ploidy had prognostic significance, with the ORs of not dying of 2.68 and 2.80, respectively. Applying multivariate analysis to RFS, 21N when adjusted for nodal status, EGFR, and DNA ploidy (full model) failed to retain prognostic value (P = .202), whereas nodal status was the most significant indicator of relapse (P = .027) followed by DNA ploidy (P = .056) and EGFR (P = .093). CONCLUSIONS: This study suggests that overexpression of the c-erbB-2 oncoprotein appears to be an important indicator of relapse in stage I-II breast cancer when singly evaluated. Multivariate analysis shows that the determination both of nodal status and DNA ploidy improves our ability to identify subsets of patients with different prognoses, and allows for a better selection of patients for systemic adjuvant treatments.

Adult↗