Breast cancer outcomes in a population with high prevalence of obesity.

BACKGROUND: Obesity has been associated with poor prognosis in breast cancer. However, most previous studies examined populations with relatively low proportions of obese patients. Given that forecasts predict obesity rates to exceed 50% by 2030, it is important to examine breast cancer outcomes in populations with higher rates of obesity. We hypothesized that obesity, as measured by body mass index (BMI), is associated with decreased overall survival and disease-free survival in patients with invasive breast cancer in a population with a high prevalence of obesity. METHODS: A retrospective review of a prospectively maintained database was conducted on patients treated for invasive breast cancer at an academic medical center between 1997 and 2013. BMI was calculated from each patient's height and weight at the time of diagnosis. Patients were categorized as normal (BMI <25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI >30 kg/m(2)), as per the definitions established by the World Health Organization. The end points of overall survival and disease-free survival were analyzed. RESULTS: A total of 523 patients with invasive breast cancer were included for analysis. Based on BMI, 87 (16%) were categorized as normal, 150 (29%) were overweight, and 286 (55%) were obese. The median follow-up was 49 mo. There were 16 deaths (18.4%) in normal patients, 25 (16.7 %) in overweight patients, and 45 (15.7%) in obese patients (P = 0.84). By Kaplan-Meier survival analysis, there were no differences in overall survival (P = 0.49) or in disease-free survival (P = 0.33) among the three groups. CONCLUSIONS: Obesity is not associated with decreased overall or disease-free survival in a patient population with a high prevalence of obesity. These findings suggest that there may be other factors that contribute to the poor prognosis of obese breast cancer patients observed in populations with lower rates of obesity.

Effect of January vacations and prior night call status on resident ABSITE performance.

OBJECTIVE: To determine if vacations in January or on-call status have an effect on American Board of Surgery In-Training Examination (ABSITE) scores. DESIGN: Retrospective review of the performance of general surgery residents on ABSITE. Data collected included ABSITE scores, United States Medical Licensing Examination Step 2 scores, January vacation schedules, and call schedules. ABSITE performance was examined for correlation with vacation or call schedules. Student t test was used for statistical analysis, with a p value of less than 0.05 considered significant. SETTING: General surgery residency program at the Louisiana State University Health Sciences Center-Shreveport, a university hospital-based program with 5 categorical residents per year. PARTICIPANTS: Postgraduate year (PGY) 1 through 5 general surgery categorical residents from 2006 to 2012. RESULTS: A total of 170 ABSITE scores from 55 residents were reviewed. The mean score when vacation was taken was 48.6 as compared with 36.3 when no vacation was taken (p = 0.02). Residents who took a January vacation at least once in their residency had a mean score of 42.8 as compared with 37.7 of those who did not (p = 0.43). The mean United States Medical Licensing Examination Step 2 score of residents who took a January vacation at least once in their residency was 218 as compared with 217 for their peers (p = 0.78). Among residents who took January vacations, the mean score in the years they took vacation was 49.4 as compared with 35.4 in the years they did not (p = 0.02). Prior night call status had no effect on the examination scores (44.2 vs 38.6, p = 0.30). CONCLUSIONS: Mean ABSITE scores were higher for residents who took a January vacation before the examination, despite no apparent difference in baseline test-taking ability. Among residents who took January vacations, mean scores were higher in the years they took vacation than in other years. On-call status did not have an effect on ABSITE performance. Vacation schedules in January can have a significant effect on ABSITE scores.

Does obesity have an effect on outcomes in triple-negative breast cancer?

BACKGROUND: Among patients with breast cancer, obesity has been associated with an increased likelihood of having triple-negative breast cancer (TNBC). This association has been thought to be due to the antiapoptotic effects of obesity-related proteins. However, the effect of obesity on the outcomes in patients with TNBC remains unclear. We hypothesized that obesity would be associated with decreased overall survival and disease-free survival in these patients. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database was conducted of patients treated for breast cancer at an academic medical center from March 1998 to September 2011. The body mass index (BMI) of patients with TNBC was calculated at diagnosis. The patients were categorized as normal (BMI < 25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI > 30 kg/m(2)). The endpoints of overall survival and disease-free survival were analyzed. RESULTS: A total of 183 patients with TNBC were included for analysis. Of the 183 patients, 24 (13.1%) were normal (BMI < 25 kg/m(2)), 42 (23.1%) were overweight (BMI 25-30 kg/m(2)), and 117 (63.7%) were obese (BMI > 30 kg/m(2)). The median follow-up period was 42.5 months. Of the 183 patients, 2 (9.1%) died in the normal group, 10 (23.1%) died in the overweight group, and 25 (21.4%) died in the obese group (P = 0.28). The patients who were overweight or obese had larger tumors (P = 0.02), a higher T stage (P = 0.001), and higher tumor grade (P = 0.01) than the normal BMI patients. By Kaplan-Meier analysis, normal patients had higher overall survival than the overweight or obese patients, but this difference was not statistically significant (P = 0.29). Disease-free survival was also not significantly different (P = 0.91). CONCLUSIONS: Despite an increased frequency of larger tumors, higher T stage, and higher tumor grade, obesity was not associated with decreased overall or disease-free survival in patients with TNBC.

Is chronic kidney disease an independent risk factor for mortality in breast cancer?

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for morbidity and mortality in multiple disease processes. However, not much is known about the relationship between breast cancer and CKD. CKD is associated with increased difficulty in breast cancer screening or surveillance due to increased calcifications on mammography. In addition, there is concern regarding the optimization of serum levels of chemotherapeutics in patients with CKD or on hemodialysis. We hypothesized that CKD is an independent risk factor for mortality in patients with breast cancer. METHODS: A case-matched, retrospective review of a prospectively maintained database was conducted on patients treated for breast cancer at an academic medical center between 1998 and 2011. Glomerular filtration rates (GFRs) were calculated for each patient at the time of diagnosis, and patients with CKD (GFR <60 mL/min) were matched in a 1:2 ratio with patients with GFR >60 mL/min, controlling for age, stage at diagnosis, and race. Primary end points measured were disease-free survival and overall survival. Statistical analysis was performed using Student t-test and Kaplan-Meier. RESULTS: Of the 1223 total patients, 54 (4%) had CKD. One hundred five patients without CKD were matched for age, stage at diagnosis, and race. Mean GFR among patients with and without CKD were 47.6 and 83.2 mL/min, respectively (P < 0.001). The 5-y overall survival was 77% for patients with CKD and 86% for patients without CKD (P = 0.47). Disease-free survival was 64% and 81%, respectively (P = 0.45). CONCLUSION: Based on our data, CKD does not appear to have a significant impact on outcomes in patients with breast cancer.

Virotherapy using a novel chimeric oncolytic adenovirus prolongs survival in a human pancreatic cancer xenograft model.

INTRODUCTION: Pancreatic adenocarcinoma is an aggressive malignancy. Oncolytic adenoviruses (Ads) are modified genetically to target tumor cells while sparing normal cells. We modified the knob domain of the Ad serotype 5 with a serotype 3 knob domain and incorporated the CXCR4 promoter to regulate Ad E1A gene expression (Ad5/3-CXCR4-E1A). These modifications were made to efficiently infect and lyse pancreatic tumors. METHODS: Human pancreatic cancer lines CFPAC-1, PANC-1, AsPC-1, and BxPC-3 were obtained from the American Type Culture Collection. Efficiency of Ad infection in the cells was determined by the use of an Ad construct expressing the green fluorescence protein (GFP) marker in place of the E1A gene (Ad5/3-CXCR4-GFP) and quantified by flow cytometry. Oncolytic activity in the pancreatic cancer cells was determined with the Ad5/3-CXCR4-E1A oncolytic Ad by a crystal violet staining method. To determine the oncolytic effect in vivo, pancreatic cancer cells were implanted on the flanks of 40 SCID mice (4 groups). Tumors were injected intratumorally for 3 days with Ad5/3-CXCR4-E1A, Ad5 wild-type (a positive control), or phosphate-buffered saline (a no virus control). Tumor size, overall survival, and body condition scale score were recorded. Statistical analyses included the Kaplan-Meier survival curve, the log-rank test, and one-way analysis of variance. RESULTS: The serotype 3 fiber-modified Ad with the CXCR4 promoter (Ad5/3-CXCR4-E1A) was most efficient in infecting and lysing pancreatic cancer cells compared with an Ad containing an unmodified fiber knob (Ad5-CXCR4-E1A). Treatment of pancreatic tumor xenografts in vivo with Ad5/3-CXCR4-E1A group resulted in smaller tumors (P = .001), greater body condition scale score (P = .01), and greater survival time (P = .04) than the other treatment groups. CONCLUSION: Ad5/3-CXCR4-E1A treatment significantly prolonged survival in SCID mice pancreatic tumor xenografts. This novel construct represents a potential new therapy against pancreatic cancer.

Outcome for patients with triple-negative breast cancer is not dependent on race/ethnicity.

Introduction. Triple negative breast cancer (TNBC) is biologically aggressive and is associated with a worse prognosis. To understand the impact of race/ethnicity on outcome for patients with TNBC, confounding factors such as socioeconomic status (SES) need to be controlled. We examined the impact of race/ethnicity on a cohort of patients of low SES who have TNBC. Methods. 786 patients with Stage 0-III breast cancer were evaluated. Of these, 202 patients had TNBC (26%). Primary endpoints were cancer recurrence and death. ZIP code-based income tract and institutional financial data were used to assess SES. Data were analyzed using Kaplan-Meier survival analysis, log-rank tests, Cox Proportional hazard regression, chi square test, and t-tests. A P value ≤0.05 was considered statistically significant. Results. Of the 468 African-Americans (60%) in the database, 138 had TNBC; 64 of 318 Caucasians had TNBC. 80% of patients had an annual income of ≤$20,000. The 5-year overall survival was 77% for African-American women versus 72% for Caucasian women (P = 0.95). On multivariate analysis, race/ethnicity had an impact on disease-free survival (P = 0.027) but not on overall survival (P = 0.98). Conclusion. In a predominantly indigent population, race/ethnicity had no impact on overall survival for patients with triple negative breast cancer.

The chemokine receptor CXCR4 as a novel independent prognostic marker for node-positive breast cancer patients.

BACKGROUND: Node-positive breast cancer patients are a high-risk group. However, not all such patients will succumb to the disease. The molecular basis for this biologic heterogeneity is poorly understood. The chemokine receptor CXCR4 is a marker of metastatic disease. Its prognostic role in node-positive patients is unknown. We postulate that high CXCR4 overexpression in node-positive breast cancer specimens predicts a poor outcome. METHODS: 185 node-positive breast cancer patients were evaluated. All had standardized treatment and surveillance protocols. CXCR4 levels were detected with Western blots. Results were quantified against 1 µg of HeLa cells. CXCR4 expression was defined as high (≥ 7.5-fold) or low (<7.5-fold). Primary endpoints were cancer recurrence and death. Statistical analyses were Kaplan-Meier curves, log-rank test, and Cox proportional hazard model, with a P-value of ≤ 0.05 as significant. RESULTS: The mean follow-up time was 54 months; 148 patients (80%) had low CXCR4 and 37 patients (20%) had high CXCR4 level. The 5-year overall survival (OS) for the low and high CXCR4 group was 69% and 57%, respectively (P=0.02). The 5-year disease-free survival (DFS) for the low and high CXCR4 group was 62% and 53%, respectively (P=0.08). On multivariate analysis, T stage (P=0.001) and grade (P=0.04) were independent predictors of DFS, while T stage (P=0.005), grade (P=0.024), and CXCR4 level (P=0.01) were independent predictors of OS. CONCLUSION: High CXCR4 level in cancer specimens independently predicts a poor outcome for patients with node-positive breast cancer.

Should a routine metastatic workup be performed for all patients with pathologic N2/N3 breast cancer?

BACKGROUND: Node-positive breast cancer patients are at risk for metastatic disease. A routine metastatic workup might or might not be necessary for all patients with N2 or N3 diseases. The National Comprehensive Cancer Network guidelines recommend a metastatic workup for patients with T3N1 disease, yet no definitive recommendations are made for N2/N3 diseases. We hypothesized that for patients with operable pathologic N2/N3 diseases, a metastatic workup should only be considered for patients with T3/T4 lesions. STUDY DESIGN: Two hundred and fifty-six patients with pathologic N2/N3 diseases were identified from a prospective breast cancer database of 1,329 patients with stage 0 to III breast cancer. A metastatic workup included chest x-rays, bone scans, CT scans, and PET scans. Primary end point was incidence of stage IV disease at the time of diagnosis or within 1 month of definitive surgery. Statistical analysis included chi-square test, independent t-test, Kaplan-Meier Survival method, log-rank test, and Cox proportional hazard model. A p value ≤ 0.05 was considered statistically significant. RESULTS: There were 158 patients with N2 disease (62%) and 98 with N3 disease (38%). Overall, 16% had stage IV disease (N2 = 15%, N3 = 16%). There was no significant difference in age (p = 0.37), tumor size (p = 0.89), tumor grade (p = 0.09), estrogen-receptor status (p = 0.23), or progesterone-receptor status (p = 0.35) between the N2 and N3 groups. Incidences of stage IV disease were T0/T1, 0%; T2, 6%; T3, 22%; and T4, 36%. Multivariate analysis demonstrated that only T stage (p = 0.0006) and grade (p = 0.026) were independent predictors of overall survival. CONCLUSIONS: A metastatic workup is only indicated for N2/N3 patients with T3 or T4 primary lesions.

Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea.

Clearly new breast cancer models are necessary in developing novel therapies. To address this challenge, we examined mammary tumor formation in the Syrian hamster using the chemical carcinogen N-methyl-N-nitrosourea (MNU). A single 50mg/kg intraperitoneal dose of MNU resulted in a 60% incidence of premalignant mammary lesions, and a 20% incidence of mammary adenocarcinomas. Two cell lines, HMAM4A and HMAM4B, were derived from one of the primary mammary tumors induced by MNU. The morphology of the primary tumor was similar to a high-grade poorly differentiated adenocarcinoma in human breast cancer. The primary tumor stained positively for both HER-2/neu and pancytokeratin, and negatively for both cytokeratin 5/6 and p63. When the HMAM4B cell line was implanted subcutaneously into syngeneic female hamsters, tumors grew at a take rate of 50%. A tumor derived from HMAM4B cells implanted into a syngeneic hamster was further propagated in vitro as a stable cell line HMAM5. The HMAM5 cells grew in female syngeneic hamsters with a 70% take rate of tumor formation. These cells proliferate in vitro, form colonies in soft agar, and are aneuploid with a modal chromosomal number of 74 (the normal chromosome number for Syrian hamster is 44). To determine responsiveness to the estrogen receptor (ER), a cell proliferation assay was examined using increasing concentrations of tamoxifen. Both HMAM5 and human MCF-7 (ER positive) cells showed a similar decrease at 24h. However, MDA-MB-231 (ER negative) cells were relatively insensitive to any decrease in proliferation from tamoxifen treatment. These results suggest that the HMAM5 cell line was likely derived from a luminal B subtype of mammary tumor. These results also represent characterization of the first mammary tumor cell line available from the Syrian hamster. The HMAM5 cell line is likely to be useful as an immunocompetent model for human breast cancer in developing novel therapies.

Chemokine receptor CXCR4 level in primary tumors independently predicts outcome for patients with locally advanced breast cancer.

BACKGROUND: Chemokine receptor CXCR4 is a marker of metastatic disease. We found initially that CXCR4 level is a predictive marker for patients with locally advanced breast cancer (LABC). We now confirm our initial observations. METHODS: We evaluated 77 LABC patients who had neoadjuvant therapy. Specimens were taken at the time of definitive operation. CXCR4 levels were detected with Western blots. CXCR4 expression >6.6-fold over known concentration of HeLa cells was defined as high. Primary endpoints were cancer recurrence and death. Statistical analyses were Kaplan-Meier curves, log-rank test, and Cox proportional hazard model. RESULTS: Median follow-up time was 42 months; 55 patients (71%) had low CXCR4 level. The 5-year overall survival for the low and high CXCR4 group was 78% and 50%, respectively (P = .015). The 5-year disease-free survival (DFS) for the low and high CXCR4 group was 67% and 41%, respectively (P = .024). On multivariate analysis, CXCR4 overexpression (P = .003) and nodal status (P = .044) were independent predictors of overall survival; CXCR4 overexpression (P = .003) and nodal status (P = .026) were also independent predictors of DFS. CONCLUSION: We confirmed that high CXCR4 levels in cancer specimens after neoadjuvant therapy independently predict a poor outcome for patients with LABC.

The role of chemokine receptor CXCR4 in the biologic behavior of human soft tissue sarcoma.

The molecular basis of sarcoma remains poorly understood. However, recent studies have begun to uncover some of the molecular pathways involved in sarcomagenesis. The chemokine receptor CXCR4 has been implicated in sarcoma development and has been found to be a prognostic marker for poor clinical outcome. There is growing evidence that overexpression of CXCR4 plays a significant role in development of metastatic disease, especially in directing tumor cells towards the preferential sites of metastases in sarcoma, lung and bone. Although further investigation is necessary to validate these pathways, there is potential for clinical application, particularly in the use of pharmacologic inhibitors of CXCR4 as means of preventing sarcoma metastasis.

CXCR4 as a predictive marker for locally advanced breast cancer post-neoadjuvant therapy.

BACKGROUND: CXCR4 is a G-protein coupled receptor that has been linked with metastasis in several cancers, including breast cancer. We recently demonstrated that high CXCR4 levels in primary tumors of patients with breast cancer had a prognostic significance. We hypothesize that patients whose tumors had a low CXCR4 overexpression level following neoadjuvant chemotherapy will have a lower recurrence rate than those whose tumors remained high. METHODS: Seventeen locally advanced breast cancer (LABC) patients were accrued, and tumor specimens were obtained before and after neoadjuvant therapy. CXCR4 levels were quantified by Western blots against 1 µg of protein from HeLa cells. The primary end-point was cancer recurrence. Statistical tests utilized include Kaplan-Meier survival analysis and log-rank test. A P value ≤ 0.05 was considered significant. RESULTS: We previously defined low CXCR4 overexpression as ≤6-fold elevation and high overexpression as >6-fold elevation over HeLa cells. Of 17 LABC tumors evaluated, 10 (59%) remained in the low group, 5 (29%) reduced from high to low overexpression, and 2 (12%) maintained a high overexpression after neoadjuvant therapy. With a median follow-up of 28 mo, patients whose tumors maintained a high CXCR4 overexpression level after neoadjuvant therapy had a significantly higher rate of cancer recurrence (P = 0.0068). CONCLUSIONS: CXCR4 was a predictive molecular marker of response to neoadjuvant chemotherapy for patients with LABC. Patients whose tumors had a persistently high CXCR4 overexpression level after neoadjuvant therapy are at a significant risk for recurrence, and therefore, should be targeted for more intensive and/or novel therapy.

Chemokine receptor CXCR4 overexpression predicts recurrence for hormone receptor-positive, node-negative breast cancer patients.

BACKGROUND: The expected outcome for hormone receptor-positive, node-negative patients should be favorable. However, some patients do develop metastatic disease and the mechanism for this observation is poorly understood. CXCR4 is a chemokine receptor that has been implicated to play a pivotal role in breast cancer growth and metastasis. Its predictive role has not been fully evaluated. We determined to see whether CXCR4 can predict outcome in this subset of patients. METHODS: We accrued and analyzed data from 101 patients with hormone receptor-positive, node-negative breast cancers. The CXCR4 level was detected using Western blots and its level was defined as either low (<6.6-fold) or high (≥6.6-fold). Primary end points were systemic cancer recurrence and death. Statistical analysis performed included Spearman's correlation, Kaplan-Meier survival analysis, and Cox proportional hazard model. RESULTS: Although benign breast tissues had an undetectable level of CXCR4, all 101 cancer specimens had overexpressed CXCR4 (mean 6.4 ± 3.4-fold). There were 79 patients in the low CXCR4 group and 22 patients in the high CXCR4 group. High CXCR4 overexpression was predictive of both cancer recurrence (P = .002) and overall survival (P = .0012). CONCLUSION: High CXCR4 overexpression in primary tumors was predictive of worse outcomes in hormone receptor-positive, node-negative breast cancer patients.

The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses.

BACKGROUND: Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and this system has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. METHODS: Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. RESULTS: Infection and replication of our tropism modified oncolytic virus has been observed in the breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing red fluorescent protein (RFP) expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 h after infection in human breast tumor slices. CONCLUSIONS: We have shown that a tropism modified oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility.

Is breast conservation therapy a viable option for patients with triple-receptor negative breast cancer?

BACKGROUND: Triple-receptor negative breast cancers (TNBC) are aggressive neoplasms that lack estrogen-receptor, progesterone-receptor, and HER-2 expressions. Comparative analysis of breast conservation therapy (BCT) versus mastectomy for TNBC is reported sparsely. We hypothesized that, despite its aggressive behavior, TNBC can be managed with BCT. METHODS: Outcomes for 202 patients with TNBC who were treated with BCT or mastectomy were analyzed. Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank, independent samples t test, Cox proportional hazard model, and Chi-square. RESULTS: BCT was performed in 30% of patients. Isolated local recurrence rate for BCT and mastectomy was 0% and 10.6%, respectively (P = .02). Isolated regional recurrence rate for BCT and mastectomy was 1.6% and 1.4%, respectively (P = .61). Neither concomitant locoregional and distant recurrence rate (P = .73) nor isolated distant recurrence rate (P = .71) was significantly different between the BCT and mastectomy groups. The 5-year overall survival (OS) was better for the BCT group than the mastectomy group (89% vs 69%; P = .018); however, this was likely due to the mastectomy group having a larger neoplasm size (T3/T4: 4% BCT vs 27% mastectomy; P = .0002), advanced N-disease (N2/3: 8% BCT vs 25% mastectomy; P = .0003), and advanced stage of disease (stage 3: 8% BCT vs 35% mastectomy; P < .0001). On multivariate analysis, surgical approach had no effect on either disease-free survival (P = .60) or OS (P = .19); only t-stage was an independent predictor of disease-free survival (P = .02), while N-stage was an independent predictor for OS (P = .03). CONCLUSION: Despite TNBC's aggressive behavior, breast conservation therapy is a viable option for selected patients with TNBC.

Impact of race and ethnicity on outcomes for estrogen receptor-negative breast cancers: experience of an academic center with a charity hospital.

BACKGROUND: African American women have a higher breast cancer mortality rate than Caucasian women. Estrogen receptor (ER)-negative tumors, which are more aggressive than ER-positive tumors, occur more frequently in African American women than in Caucasian women and may contribute to apparent disparities in outcomes. However, outcome results need to be controlled for socioeconomic status (SES). We evaluated the effect of race and ethnicity on outcomes of patients with ER-negative tumors by determining outcomes in African American and Caucasian women with low SES but similar access to care. STUDY DESIGN: From a prospective database of 786 patients with stage 0 to III breast cancer, all 375 patients with ER-negative tumors were evaluated. Patients received standard definitive operations and adjuvant treatment. Compliance with treatment was more than 90%. Primary endpoints were cancer recurrence and overall survival (OS). Statistical analysis performed included Kaplan-Meier survival analysis, log-rank test, Cox proportional hazard model, Student's t-test, and chi-squared test. A p value < or = 0.05 was considered statistically significant. RESULTS: Fifty-four percent of African American patients had ER-negative tumors versus 39% in Caucasian patients. In both groups, 69% of patients received free care or Medicaid, with a median income of $16,577 (range $15,367 to $36,788). Comparing the 2 racial and ethnic groups, mean tumor size (p = 0.19), tumor grade distribution (p = 0.32), nodal distribution (p = 0.50), stage distribution (p = 0.30), rate of mastectomy (p = 0.47), receipt of adjuvant chemotherapy (p = 0.07), and financial class distribution (p = 0.67) were not significantly different. The 5-year OS was 77% for both groups (p = 0.59). On multivariate analysis, race and ethnicity were not independent predictors of OS (p = 0.73). CONCLUSIONS: In a predominantly indigent population, race and ethnicity had no impact on outcomes for ER-negative breast cancer.

High chemokine receptor CXCR4 level in triple negative breast cancer specimens predicts poor clinical outcome.

INTRODUCTION: Basal-like tumors or triple negative breast cancers are those that lack hormone-receptor and HER-2 expressions. They are considered to be aggressive tumors, and molecular mechanism to account for this is poorly understood. CXCR4 is a chemokine receptor that has been linked to breast cancer invasion and metastasis. We postulate that high CXCR4 overexpression level in cancer specimens predicts a poor outcome in patients with triple negative breast cancers. METHODS: One hundred fifty-one patients with triple negative breast cancers were prospectively accrued and analyzed. All had undergone standardized treatment and surveillance protocols. From each specimen, CXCR4 levels were detected using Western blots. Results were quantified against 1 microg of HeLa cells (positive controls). CXCR4 expression was defined as high (>or=6-fold) or low (<6-fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model. RESULTS: At a median follow-up of 37 mo, patients whose tumors had high CXCR4 overexpression (>or=6-fold) had a significantly higher incidence of cancer recurrence (P=0.014) and cancer-related death (P=0.026) than those in the low CXCR4 group (<6-fold). After adjusting for tumor size and nodal status, the relative risk for cancer recurrence and death in the high CXCR4 group was 2.1-fold (P=0.007; 95% CI: 1.22 to 3.8) and 2-fold (P=0.047; 95% CI: 1.01 to 4.06) higher than those in the low CXCR4 group, respectively. CONCLUSION: High CXCR4 overexpression in cancer specimens predicts a worse outcome in patients who have triple negative breast cancer.

Predictive value of eIF4E reduction after neoadjuvant therapy in breast cancer.

INTRODUCTION: Initiation factor 4E (eIF4E) overexpression has prognostic significance in breast cancer. Up-regulation of downstream gene products associated with high eIF4E overexpression has been linked to chemoresistance. We hypothesize patients whose tumors had eIF4E reduction after neoadjuvant chemotherapy will have lower cancer recurrence compared with those who did not. METHODS: Seventeen locally advanced breast cancer patients were accrued, and tumor specimens were obtained before and after neoadjuvant therapy. eIF4E was quantified by Western blots. Primary end-point was cancer recurrence. RESULTS: Low eIF4E was defined as < or =7.5-fold elevation and high eIF4E was >7.5-fold elevation. Of 17 patients, six tumors remained low after neoadjuvant therapy, six dropped from high to low eIF4E, and five remained high. With a median follow-up of 29 mo, four of five patients with tumors that remained high have recurred while only three of 12 patients in the low eIF4E post-therapy group have recurred (P=0.05, chi(2)). Survival analysis using the Kaplan-Meier method showed a higher rate of cancer recurrence in patients with post-treatment high eIF4E overexpression (P=0.026, log rank test). CONCLUSIONS: Breast cancer patients whose tumors had low eIF4E overexpression after neoadjuvant chemotherapy had lower cancer recurrence compared with those who did not.

Race/Ethnicity has no effect on outcome for breast cancer patients treated at an academic center with a public hospital.

BACKGROUND: African American women have a higher breast cancer mortality rate than Caucasian women. To understand this difference, socioeconomic status (SES) needs to be controlled, which can be achieved by evaluating outcome within a population that is underinsured or low SES. We elected to examine the effect of race/ethnicity on outcome of patients with operable breast cancer by evaluating outcome in a population with low SES and similar access to care. METHODS: From a prospective breast cancer database created in 1998, we examined outcome for 786 patients with stage 0 to III breast cancer treated up to September 2008. Patients were treated at Louisiana State University Health Sciences Center in Shreveport and E.A. Conway Hospital and the majority received standard definitive surgery as well as appropriate adjuvant treatment. Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank test, Cox proportional hazards model, independent-samples t test, and chi(2) test. P