Survival In Breast Carcinoma Research Articles

Cytoplasmic HuR Expression Is a Prognostic Factor in Invasive Ductal Breast Carcinoma

HuR is a ubiquitously expressed mRNA-binding protein. Intracellular localization of HuR is predominantly nuclear, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm it can stabilize certain transcripts. Because nucleocytoplasmic translocation of HuR is necessary for its activity, it was hypothesized that cytoplasmic HuR expression in cancer cells could be a prognostic marker. To test the significance of HuR in carcinogenesis of the breast, we have investigated HuR expression in a mouse mammary gland tumor model and from 133 invasive ductal breast carcinoma specimens. HuR expression was elevated in the cyclooxygenase-2 transgene-induced mouse mammary tumors, and its expression was predominantly cytoplasmic in the tumor cells. In the human carcinoma samples, high cytoplasmic immunoreactivity for HuR was found in 29% (38 of 133) of the cases. Cytoplasmic HuR expression associated with high grade (P = 0.0050) and tumor size over 2 cm (P = 0.0082). Five-year distant disease-free survival rate was 42% [95% confidence interval (95% CI), 26-58] in cytoplasm-high category and 84% (95% CI, 76-91) in cytoplasm-negative or -low category (P < 0.0001), and high cytoplasmic expression of HuR was an independent prognostic factor in a Cox multivariate model (relative risk 2.07; 95% CI, 1.05-4.07). Moreover, high cytoplasmic HuR immunopositivity was significantly associated with poor outcome in the subgroup of node-negative breast cancer in a univariate analysis (P < 0.0007). Our results show that high cytoplasmic HuR expression is associated with a poor histologic differentiation, large tumor size, and poor survival in ductal breast carcinoma. Thus, HuR is the first mRNA stability protein of which expression associates with poor outcome in breast cancer.

A functional polymorphism of the tumor necrosis factor receptor-II gene associated with the survival and relapse prediction of breast carcinoma

Objective Recently, we showed the implication of the polymorphism in tumor necrosis factor-alpha (TNF-α) gene in the susceptibility and prognosis of breast carcinoma. TNF-α acts through its receptors: types I and II. The TNFRII, expressed on the haematopoietic cells, is the high affinity receptor involved in mediating the biological effects of TNF-α. We investigated the susceptibility and prognostic implications of the genetic variation in the TNFRII in breast carcinoma. Methods We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNFRII gene in 300 unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations of the genetic marker with the rates of the breast carcinoma-specific overall survival and the disease-free survival were assessed. Results A significant association was found between TNFRII-196 M/R heterozygous genotype and breast carcinoma (OR = 1.61; P = 0.02). This association was more significant in post-menopausal patients (OR = 2.41, P = 0.0001). The 196 R-TNFRII allele showed a significant association with increased overall survival and disease-free survival in breast carcinoma patients. Conclusion Genetic variation in TNFRII may predict the late onset of breast carcinoma, relapse and death for patients with breast carcinoma.

High preoperative serum TIMP-1 is a prognostic indicator for survival in breast carcinoma

The amount of the immunoreactive protein for the tissue inhibitor of the matrix metalloproteinase-1 (TIMP-1) was studied prospectively from the pretreatment sera of 71 breast carcinoma patients using an enzyme-linked immunoassay (ELISA). The study consisted of patients with a primary breast carcinoma diagnosed between 1988 and 1991. The median follow-up time was more than 10 years, and routine adjuvant treatment was not used in the primary treatment. High TIMP-1 (> 196 ng/ml) was found to correlate with a poor relapse-free survival (RFS) in primary node-negative breast carcinoma. After 10 years of the follow-up only 42% of the patients with a high preoperative serum TIMP-1-level were free of the relapse, whereas 82% of the patients with a low serum TIMP-1 enjoyed a long RFS-time (log rank p =0.009). High serum TIMP-1 also indicated poor RFS (p = 0.02) and overall survival (p = 0.05) in stage I breast carcinoma. In Kaplan-Meier analysis the RFS was 89% in patients with a low serum level of TIMP-1 compared to 52% in patients with a high serum concentration of TIMP-1. In conclusion, preoperative high serum TIMP-1 levels predict poor outcome in primary breast carcinoma. In multivariate analysis preoperative high serum TIMP-1 increases the risk of relapse 3.4-fold during the first 10 years of follow-up in primary node-negative breast carcinoma.

Outcome Analysis of Patients with Early Infiltrating Breast Carcinoma Treated by Surgery with Intraoperative Evaluation of Surgical Margins

The purpose of this study was to determine the effect of intraoperative evaluation of surgical margins (IESM) on the local recurrence rate, the occurrence of distant metastases and survival in invasive breast carcinoma (T1-2). Two groups of patients were compared: a control group of 149 patients treated by classical quadrantectomy without IESM, and an IESM study group of 102 patients submitted to surgical treatment guided by this procedure. In the IESM group 64 quandrantectomies, 33 enlarged quadrantectomies and five mastectomies were performed. In the control group 17 local recurrences (11.4%), 49 distant metastases (39.2%) and 43 deaths (31.5%) occurred; in the IESM group there were no local recurrences, nine distant metastases occurred (8.8%) and three patients died (2%). Adjuvant treatment was the same in both groups. The survival curves were estimated by the Kaplan-Meier method and compared with the log-rank test. The curves were censored at 99 months of follow-up for adequate comparison because the follow-up period was different in the two groups. Significant differences in local recurrence-free survival and distant metastasis-free survival curves (P = 0.001) in favor of the study group were observed. The overall survival curve of the IESM group was also superior, but statistical analysis revealed only a strong tendency without significance (P = 0.06). Treatment of early infiltrating breast carcinoma guided by IESM results in a better prognosis.

Preoperative serum MMP-9 immunoreactive protein is a prognostic indicator for relapse-free survival in breast carcinoma

The immunoreactive protein for the matrix metalloproteinase-9 (MMP-9) was studied prospectively from the pre-treatment sera of breast carcinoma patients using an enzyme-linked immunoassay (ELISA). The study comprised 71 primary breast carcinoma patients treated in Oulu University Hospital, Finland, between 1988 and 1991. The median follow-up time was over 10 years. Low preoperative serum MMP-9 (<54.5 ng/ml) was found to correlate with a poor relapse-free survival (RFS) in primary breast carcinoma. After 10 years of follow-up only 43% of the patients with low serum MMP-9 were disease-free, whereas 76% of the patients with high serum MMP-9 lived free of the disease (log-rank P=0.008). Low serum MMP-9 also indicated poor RFS in node-negative ( P=0.03), stage I–II ( P=0.01), progesterone receptor negative ( P=0.008) carcinoma as well as in patients <50 years ( P=0.02) with primary breast carcinoma. There was no statistical difference in overall survival. In multivariate analysis, preoperative low serum MMP-9 increases the risk of relapse 3.0-fold during the first 10 years of follow-up in primary breast carcinoma.

Correlation of standard histological features and biomarkers with overall survival in breast carcinoma

9683 Background: More than 100 variables have been described to predict prognosis in breast cancer but only maximum tumour size (T), histological grade, nodal status, ER and HER-2 are routinely incorporated into clinical practice. In this study both classic histological features and novel biomarkers using immunohistochemistry (IHC) were evaluated to assess overall survival. Methods: Formalin fixed paraffin embedded tissue was collected from 414 breast cancer patients with invasive ductal carcinoma. 247 patients were node negative. Median follow-up was 110 months (Range 1–148 months). Routine histological parameters were assessed and a number of antigens including ER, PR, HER-2, p53, Ki67 and microvessel density were evaluated using IHC. ER, PR, HER-2 and p53 were assessed semiquantitatively using the Quickscore method. Microvessel density was counted over a 200x field and adjusted to mm2, and 500 tumour cells were counted for assessment of Ki67. Tumour size was estimated using T while volume was modeled as an ellipsoid. Results: With univariate analysis, grade (p <0.001), nodal status (p <0.001), tumour volume (p <0.01), HER-2 (p = 0.006), Ki67 (p <0.001), mitotic rate (p <0.001) and T (p <0.001) were statistically significant. For node negative patients grade (p = 0.02), tumour volume (p = 0.03) and mitotic rate (p = 0.009) were significant. Using multivariate analysis, mitotic rate (p = 0.0005) and tumour volume (p <0.001) predicted nodal involvement, and grade (p = 0.002), nodal status (p = 0.001) and T (p <0.001) predicted overall survival. Conclusions: This analysis validates the current staging system. Additional IHC markers failed to predict overall survival when standard histological features were utilised. Mitotic rate and tumour volume were independent predictors of nodal metastases. Tumour volume estimation may be superior to T in predicting nodal metastases and requires further evaluation to determine its potential role in staging. No significant financial relationships to disclose.

Correlation of standard histological features and biomarkers with overall survival in breast carcinoma

9683 Background: More than 100 variables have been described to predict prognosis in breast cancer but only maximum tumour size (T), histological grade, nodal status, ER and HER-2 are routinely incorporated into clinical practice. In this study both classic histological features and novel biomarkers using immunohistochemistry (IHC) were evaluated to assess overall survival. Methods: Formalin fixed paraffin embedded tissue was collected from 414 breast cancer patients with invasive ductal carcinoma. 247 patients were node negative. Median follow-up was 110 months (Range 1–148 months). Routine histological parameters were assessed and a number of antigens including ER, PR, HER-2, p53, Ki67 and microvessel density were evaluated using IHC. ER, PR, HER-2 and p53 were assessed semiquantitatively using the Quickscore method. Microvessel density was counted over a 200x field and adjusted to mm2, and 500 tumour cells were counted for assessment of Ki67. Tumour size was estimated using T while volume was modeled as an ellipsoid. Results: With univariate analysis, grade (p <0.001), nodal status (p <0.001), tumour volume (p <0.01), HER-2 (p = 0.006), Ki67 (p <0.001), mitotic rate (p <0.001) and T (p <0.001) were statistically significant. For node negative patients grade (p = 0.02), tumour volume (p = 0.03) and mitotic rate (p = 0.009) were significant. Using multivariate analysis, mitotic rate (p = 0.0005) and tumour volume (p <0.001) predicted nodal involvement, and grade (p = 0.002), nodal status (p = 0.001) and T (p <0.001) predicted overall survival. Conclusions: This analysis validates the current staging system. Additional IHC markers failed to predict overall survival when standard histological features were utilised. Mitotic rate and tumour volume were independent predictors of nodal metastases. Tumour volume estimation may be superior to T in predicting nodal metastases and requires further evaluation to determine its potential role in staging. No significant financial relationships to disclose.

Expression of the forkhead transcription factor FOXP1 is associated with estrogen receptor alpha and improved survival in primary human breast carcinomas.

The FOXP1 protein belongs to a functionally diverse family of winged-helix or forkhead transcription factors that have diverse roles in cellular proliferation, differentiation, and neoplastic transformation. The FOXP1 gene, which maps to 3p14, shows common loss of heterozygosity in breast tumors and is a candidate tumor suppressor gene. However, its role in breast cancer is unknown. We have therefore investigated the pattern of FOXP1 expression in whole sections from normal (n = 16) and neoplastic (n = 90) breast tissues and correlated the level of expression in 283 invasive breast carcinomas on tissue microarrays with clinicopathological factors and survival. Because a relationship with estrogen receptor (ER) was identified, estrogen (17beta-estradiol) regulation and ER/FOXP1 colocalization was also investigated. Expression of FOXP1 was significantly positively associated with ER (P = 0.03) and negatively with epidermal growth factor receptor (P = 0.01) but no association with age (P = 0.91), lymph node status (P = 0.94), size (P = 0.76), or grade (P = 0.22). In a multivariate analysis of survival, FOXP1 expression was associated with a significantly improved relapse-free (P = 0.03) and borderline overall (P = 0.09) survival. Unlike normal breast, there was common coexpression of FOXP1 and ER in cell lines and tumors, but no 17beta-estradiol (10(-9) m) regulation of FOXP1 in MCF-7 cells was demonstrated. Our findings support a role for FOXP1 as a potential ER coregulator in human breast carcinoma and suggest that it may also independently regulate additional important pathways that control the progression of breast cancer.

Occult metastases in axillary lymph nodes as a predictor of survival in node-negative breast carcinoma with long-term follow-up.

Increased detection rate in the lymph nodes is seen with serial sectioning or immunohistochemistry (IHC), but the importance of occult metastases is not resolved. IHC is still not recommended in routine examination of lymph nodes. Axillary lymph nodes from 385 node-negative breast cancer patients with a median follow-up of 25 years were examined with IHC for cytokeratins, applied on routine sections. The association between classic histopathologic prognostic factors and the presence of occult metastases was evaluated. Metastases were found in 45 of 385 cases (12%), 21 metastases (47%) measured < or =0.2 mm, 8 (18%) were larger than 2 mm; 14 metastases were located in the subcapsular sinus, 22 in the parenchyma of the lymph node; and 51% (23/45) of the metastases were recognized on hematoxylin-eosin staining on "second look." The detection of metastases was significantly associated with the number of sectioned lymph nodes (6% metastases for one to five lymph nodes examined versus 17% for more than five lymph nodes) and with histologic subtype (metastases in 11% of the ductal versus 33% of the lobular carcinomas). No significant association was found between occult metastases and age, tumor size, histologic grade, estrogen or progesterone receptor status, p53, or c-erbB-2. Metastases larger than 2 mm predicted a poorer recurrence-free survival rate for the whole series. A subcapsular location of the metastases was a strong predictor of overall survival. Whether or not the metastases could be identified on hematoxylin-eosin sections did not have any prognostic significance. In the multivariate analysis, histologic grade, tumor size of the primary tumor, progesterone receptor status, and the presence of occult metastasis in the lymph nodes had a prognostic impact on survival with a 25-year follow-up.

Prognostic significance of axillary node and infraclavicular lymph node status after mastectomy

Aims: The American Joint Committee on Cancer staging system for breast carcinomas has been revised. According to this revised staging system, metastasis to infraclavicular lymph nodes and number of positive axillary nodes have prognostic significance and a new stage, stage IIIC, has been introduced. The aim of this study is to investigate the association of positive axillary nodes by level and number with survival and stage migration between the old and the new stages in a lage series of mastectomy patients.Methods: Data from 1277 consecutive breast cancer patients treated by mastectomy were studied, retrospectively. Prognostic value of number of positive axillary nodes and entirely invasion of apex axillary nodes were analysed. Survival curves were generated by Kaplan–Meier method, and multivariate analysis was performed by Cox proportional hazard model.Results: Five-year survival rates for metastasis to axillary level III and for stage IIIC breast cancer were 35.4 and 38.2%, respectively. Metastases to apex axillary nodes, 4–9 and 10 or more positive lymph nodes were found to be adverse and independent prognostic factors for survival in lymph node positive patients.Conclusion: Invasion of infraclavicular nodes and 4–9 and ≥10 positive axillary lymph nodes were independent predictors for survival in node positive breast carcinomas in this series. Patients with the new stage IIIC had the worst survival among breast cancer patients.

Matrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinoma.

Adjuvant therapy is one of the major advances in the treatment of breast carcinoma patients – but do all patients need it? New predictive markers, which are able to save breast carcinoma patients from the most toxic adjuvant therapies, are still needed. The expression of matrix metalloproteinases (MMP-2) has been previously linked to invasiveness of carcinoma cells. In this study, we explored the role of MMP-2 as a prognostic factor in breast carcinoma in a large series to be able to show the favourable effect of MMP-2 negativity in poor prognosis subgroup of hormone receptor-negative patients. The MMP-2 immunoreactive protein was evaluated from primary adenocarcinoma of the breast in 453 cases by using a specific monoclonal antibody in immunohistochemical stainings. The MMP-2 protein found in breast carcinoma tumour cells was here shown to be associated with a shortened recurrence-free survival or relative overall survival (P=0.03). It was shown here that MMP-2 negativity is significantly linked to favourable prognosis in patients considered to be at risk due to their hormone receptor negativity. In the patient group presenting with a progesterone receptor-negative tumour, the survival rate of the MMP-2-positive cases was 58% while it was 95% in MMP-2-negative cases after 10 years of follow-up (P=0.005). The present data shows for the first time that MMP-2 negativity could serve as a marker for favourable prognosis in breast carcinoma patients with a hormone receptor-negative tumour usually associated with high risk. MMP-2 is also shown to correlate to shortened survival independent of major prognostic indicators in patients with primary breast carcinoma.

Widening disparity in survival between white and African-American patients with breast carcinoma treated in the U. S. Department of Defense Healthcare system.

In the U. S., age-adjusted breast carcinoma mortality rates among white and African-American women have been diverging during the last 20 years. Some investigators speculate that the widening disparity is due to inequalities in access to healthcare, with African Americans having less access to necessary healthcare and improved therapies. Others argue that differences in tumor biology or some extrinsic influences on cancer etiology and behavior may account for the widening disparity. To examine this issue further, the authors compared trends in survival among white and African-American women diagnosed with breast carcinoma in the U. S. Department of Defense (DoD), an equal access healthcare system. The medical records of all women diagnosed with primary breast carcinoma between 1980-1999 were retrieved from the U. S. DoD Automated Central Tumor Registry (ACTUR). Variables selected for further analysis were date of diagnosis, date of birth, vital status and date of death if applicable, race (black, white, and others), and stage of tumor. Because the database does not contain causes of death, overall survival was investigated. The effect of year of diagnosis and race on overall survival was analyzed using the Cox proportional hazards model stratified by age at diagnosis (1-year age groups). Calculations were performed separately by disease stage for all stages combined and stratified by stage. Statistical analyses were performed using the statistical software package SAS. After deleting observations with missing or implausible information regarding patient age, gender, and follow-up time, the final dataset was comprised of 23,612 women with primary breast carcinoma. The survival of African-American women compared with white women demonstrated an increasing ratio with calendar period. Although the hazard ratio was 1.269 for women diagnosed with breast carcinoma during the calendar period 1980-1984, it increased to 1.849 for those diagnosed between 1995-1999, which is a ratio of 1.46. For this period, the interaction between race and period was found to be significant (P = 0.04). The results of the current study demonstrated that breast carcinoma survival rates among white and African-American patients, adjusted for age and stage, are diverging in the U. S. DoD healthcare system. Thus, inequalities in access to healthcare most likely are not solely responsible for the widening racial disparities in outcome reported among women diagnosed with breast carcinoma.

Prognostic factors affecting survival and disease-free survival in lymph node-negative breast carcinomas.

The objective of this study was to identify the patients who are at low or high-risk by defining the prognostic factors in node-negative breast carcinomas. Medical records of 384 consecutive breast cancer patients with negative axillary lymph nodes who had been operated on between January 1994 and January 1997 at our hospital were retrospectively reviewed. Several clinical and pathological characteristics of patients were categorized. Univariate analyses of survival and disease-free survival (DFS) were performed by the Kaplan-Meier method and the log-rank test. Independent prognostic and predictive factors affecting survival and DFS were assessed by Cox proportional hazard method. 5-year survival and DFS were 91.4 and 85.7%, respectively. Size, grade, age, and lymphovascular invasion (LVI) were the prognostic factors that independently affected survival and DFS. Tamoxifen improved survival and DFS. While age younger than 35 was an adverse factor for both survival and DFS, age older than 49 was a detrimental factor for DFS. Patients who have a tumor with size greater than 2 cm, with histologic grade 3, with LVI, and patients with age under 35 or older than 49 have poorer prognosis among node-negative breast carcinomas, and are candidates for adjuvant therapy.

Inflammatory breast carcinoma and noninflammatory locally advanced breast carcinoma: distinct clinicopathologic entities?

Inflammatory breast carcinoma (IBC) and noninflammatory locally advanced breast carcinoma (LABC) are both associated with poor prognosis; however, whether they are distinct clinicopathologic entities remains controversial. To determine whether IBC and LABC were different, we compared tumor characteristics, prognosis, and age-specific incidence rate patterns in the Surveillance, Epidemiology, and End-Results program. An age of 50 years served as a surrogate marker for menopause. Younger age at diagnosis, poorer tumor grade, and negative estrogen receptors (ERs) were more predictive of IBC (n = 2,237) than of LABC (n = 7,985). Breast carcinoma survival was worse for patients with IBC than for those with LABC (log-rank test, P <.0001). Age-specific incidence rates for IBC increased until 50 years and then flattened, whereas rates for LABC increased for all ages. When rates for LABC were stratified by estrogen receptor-positive (ERP) and -negative (ERN) expression, rates for ERP and ERN diverged; that is, rates for ERP increased with advancing age, whereas rates for ERN flattened after 50 years. When rates for IBC were stratified by ER expression, rates for both ERP and ERN flattened after 50 years of age. IBC and LABC seemed to be distinct biologic entities, as indicated by different prognostic factor profiles and age-specific incidence rate patterns. Rates that increased before 50 years and then stabilized, possibly indicated that premenopausal exposures had a greater effect on maintaining rates for IBC than for LABC.

Racial disparities in breast carcinoma survival rates: seperating factors that affect diagnosis from factors that affect treatment.

Black females have lower breast carcinoma survival rates compared with white females. One possible reason is that black females have more advanced-stage breast disease. Another factor may be racial differences in the utilization of cancer treatments. The authors determined racial differences in 6-year stage specific survival rates, adjusting for age and treatments (using estrogen receptor [ER] status), to determine whether there were racial differences in treatment. Racial differences in the stage distributions of breast disease were used to examine the impact of racial factors on breast carcinoma diagnosis. For all breast carcinoma cases, the stage specific 6-year survival rates, in general, were significantly lower for black females for all stages combined and for Stages I-III in every age group. However, examination by different treatments, as measured by ER status, revealed some different results. Only black women younger than age 50 years with ER-positive tumors and women younger than age 65 years with ER-negative tumors had significantly lower stage-specific survival rates. In addition, the stage distribution analyses showed that black females of every age group had less Stage I breast disease. For younger black women (younger than age 50 years), there was evidence of racial differences in treatment for both women with ER-positive tumors and women with ER-negative tumors, as indicated by their lower stage-specific survival rates. In contrast, for black females age 65 years or older with ER-positive or ER-negative tumors, the lack of a significant difference in the stage-specific survival rate suggests that Medicare may help to alleviate racial disparities in cancer treatment. Furthermore, racial differences in the stage distributions indicated the need for earlier diagnosis for black females of every age.

Socioeconomic status and breast carcinoma survival in four racial/ethnic groups: a population-based study.

Although overall survival for invasive breast carcinoma remains high, black women experience poorer survival than whites. Less is known about the survival of Hispanics and Asians, who may share clinical and socioeconomic risk factors similar to blacks. To better understand racial/ethnic survival patterns, we investigated the effect of socioeconomic status (SES) and disease stage on racial/ethnic differences in breast carcinoma survival in a large population-based cohort. Using data from the Surveillance, Epidemiology, and End Results program (SEER), we identified 10,414 white, 940 black, 1100 Hispanic, and 1180 Asian females diagnosed with breast carcinoma in the Greater San Francisco Bay Area between 1988 and 1992. We used the Kaplan-Meier method to generate survival rates and Cox proportional hazards regression to estimate the risk of death by race/ethnicity, after adjustment for clinical, demographic, and census-derived SES variables. The 10-year unadjusted survival rates were 81% for whites, 69% for blacks, 75% for Hispanics, and 79% for Asians. Adjusting for stage decreased the relative risk of mortality for blacks from 1.81 to 1.29; the stage-adjusted relative risk for Hispanics (1.11) and Asians (1.02) did not differ significantly from whites. Additional adjustment for age, tumor characteristics, and treatment factors did little to alter the relative risk in blacks; adding blue-collar status to the model further decreased the relative risks for blacks to 1.22. Residing in a blue-collar neighborhood was independently associated with a 1.16 increase in risk of death. After adjustment for multiple factors, blacks continue to have slight but significantly poorer survival after breast carcinoma compared with whites, whereas the survival of Hispanics and Asians did not differ from whites.

An evaluation of the prognostic significance of vascular endothelial growth factor in node positive primary breast carcinoma

Angiogenesis is intimately related to the growth and progression of tumours and must be induced to facilitate growth beyond a minimum size. It has been implicated in the development of metastases and survival in breast carcinoma. VEGF is a cytokine that plays an important role in angiogenesis. Its expression is increased in solid tumours during induction of angiogenesis and it has been implicated as a prognostic marker in patients with node negative breast carcinoma. We studied VEGF expression, in a series of patients with node positive breast carcinoma and examined histopathological parameters of the tumour and the prognostic value of VEGF expression. Specimens from 108 cases of node positive breast cancer were stained for VEGF using an antibody suitable for use on formalin fixed tissue. VEGF staining was cytoplasmic and was scored by intensity and the percent positive cells. Patients with positive VEGF staining (n=48) were compared with patients with negative VEGF staining (n=60). Demographic criteria were similar in both groups. Only one (12%) patient with lobular carcinoma and one (14%) patient with medullary carcinoma expressed VEGF compared with 46 (49%) patients with ductal carcinoma (NOS). DCIS was present in 60 tumours. There was a strong correlation between staining in DCIS and the adjacent invasive tumours. There was no significant association between VEGF staining and T stage, tumour size or the number of positive lymph nodes. VEGF expression had no prognostic significance either for disease-free or overall survival in patients with node positive disease. This study failed to support a role for VEGF as a prognostic marker in patients with node positive breast carcinoma.

Breast microcalcifications: multivariate analysis of radiologic and clinical factors for carcinoma.

Screening mammography contributes to the improvement of breast carcinoma survival through early detection and treatment of non-palpable lesions. Microcalcifications are of fundamental importance in this process. The percentage of malignant lesions found in biopsies for microcalcifications varies from 10% to 40%. The purpose of this study was to evaluate the relationship between clinical and radiologic records and the presence of malignant breast diseases. To establish the basis for the study, 211 mammographic files showing clustered microcalcifications from 204 women were prospectively reviewed and clinical records were retrospectively drawn. Definitive pathologic analysis was available for all. The value for cancer of each criterion was investigated by univariate and multivariate analyses. A first analysis was performed on the entire population and a second one was performed with stratification on morphologic subgroups. There were 99 malignant lesions (47%). In the entire group, no clinical criterion was significant. In the univariate analysis, five radiologic variables were significant: morphologic type(p < 0.0001), number of calcifications per cluster(p < 0.0001), linear or triangular distribution(p < 0.0002), diameter of the area (p < 0.01),and number of clusters (p = 0.011). In the multivariate analysis, two criteria remained significant: morphologic type 4 (irregularly punctiform) or 5 (vermicular) microcalcifications(Le Gal's classification) (p < 0.0001) and diameter of the cluster larger than 25 mm (p = 0.032). In subgroups,in the multivariate analysis, the "age > 60 years" criterion was statistically significant in the group of regular punctiform microcalcifications (type 2); for irregularly punctiform microcalcifications (type 4), "number of microcalcifications > 20" was significant. The morphologic features of microcalcifications must be the first criterion evaluated. They permit identification of characteristically benign (annular calcifications) or malignant calcifications (vermicular calcifications). For the remainder of the calcification types, other criteria must be taken into account, and their value vary with (according to) the morphologic aspect. These findings have implications for the management of women with microcalcifications and could help breast specialists make treatment decisions.

BAG-1, an anti-apoptotic tumour marker.

BAG-1 is a multifunctional and anti-apoptotic or anti-cell death protein that interacts with a variety of cellular proteins and affects their functions. On the cell surface, it binds to the cytosolic domain of the growth factor receptors and enhances the protection from cell death triggered by growth factor receptors. In the cytosol, it binds to Bcl-2 and heat shock protein, and modulates their functions. In the nucleus, it binds to a variety of nuclear hormone receptors and inhibits hormone-induced apoptosis. BAG-1 is widely overexpressed in a variety of tumour cell lines and cancer tissues. In addition, differential expression of BAG-1 isoforms has been observed. Preclinical studies indicate that overexpression of BAG-1, especially its nuclear and cytoplasmic isoforms, may be useful as a prognostic and/or predictive biomarker. Pilot clinical studies have demonstrated that overexpression of nuclear BAG-1 may be associated with a shorter survival in breast and laryngeal carcinomas. Conversely, overexpression of cytoplasmic BAG-1 may be associated with a better clinical outcome in early stage breast cancer and in non-small cell lung cancer. Further large-scale clinical studies are warranted to establish the role of BAG-1 as a novel prognostic and/or predictive biomarker in the clinical management of these common malignancies.

Prognostic significance of the number of lymph nodes examined in patients with lymph node‐negative breast carcinoma

BACKGROUND A recent report suggested that the number of lymph nodes examined was a strong predictor of survival in patients with lymph node-negative breast carcinoma. Among women who had ≥ 20 lymph nodes examined, the risk of dying from breast carcinoma within 5 years was increased nearly 4-fold compared with women who had fewer lymph nodes examined. Because these findings were based on a relatively small cohort of patients, corroborative studies with larger patient populations were needed. METHODS The authors studied the relation between the number of lymph nodes examined and breast carcinoma survival among 911 women with lymph node-negative breast carcinoma with a median length of follow-up of 84 months. The association between other prognostic indicators and survival and the number of lymph nodes examined also was investigated. RESULTS The number of lymph nodes examined was not found to be associated with either 5-year or long-term survival. The proportion of women dying from breast carcinoma was the same (8%) in both groups (those patients with ≥ 20 lymph nodes examined vs. those in whom < 20 lymph nodes were examined) and the hazard ratio was 0.98 (95% confidence interval, 0.58–1.64). CONCLUSIONS In this larger study population, the authors failed to confirm the findings of an earlier investigation in which having a larger number of lymph nodes examined was associated with poorer survival. This finding suggests that it is unlikely the number of lymph nodes examined is an important prognostic indicator in patients with lymph node-negative breast carcinoma. Cancer 2001;91:2258–62. © 2001 American Cancer Society.