INTRODUCTION The primary aim in the management of DCIS is the prevention of recurrence and contralateral tumor (CT). Previous studies reported that younger patients and African Americans (AAs) experience a higher risk of recurrence, second tumors and show worse overall survival. Nevertheless, risk factors for DCIS recurrence, treatments and outcome are still widely discussed. The aim of our analysis was to identify clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma (MIC). METHODS In the Thomas Jefferson University Tumor Registry, we identified 820 patients with DCIS and 61 with MIC treated between 2003 and 2013. Associations between recurrence and demographic factors, histopathological features and treatment were assessed. RESULTS The median age was 59 years with a racial distribution of 69.3% white, 19.5% AAs and 5.7% Asian. There was no significant difference in age at diagnosis by ethnicity and, 64.8% was ER/PR positive and 10.1% was HER2 positive. The associations of age and ethnicity with hormone status and HER2 status were not statistically significant. To date, 73 (8%) patients developed locoregional recurrence or CT, 50 (68.5%) of which were in situ lesions. Only one patient had MIC in primary lesion. There was no significant difference in age, while white women had higher recurrence rate than Asians and AAs (9% vs. 4%). ER/PR negative women were more likely to develop recurrence than ER/PR positive (16% vs. 8%). The hormonal status of primary DCIS and recurrences was concordant in 89% of cases. Moreover, 43.5% of recurrences were HER2 3+ and 23% were HER2 2+ (FISH unknown). Mastectomy was performed in 26.3% of patients and 73.1% had conservative surgery. Women who received conservative surgery were significantly older, while there were no significant ethnic differences. Among women who underwent conservative surgery, the 41.4% that received radiation therapy (RT) were significantly less likely to develop recurrence than the 53.2% that did not. However, there was no significant difference in recurrence between mastectomy and conservative surgery with RT. Among ER/PR positive patients, the 30% that received preventive hormone therapy was significantly less likely to develop recurrence than the 61.4% that did not. CONCLUSION Our study confirms that ER/PR negative DCIS is associated with significantly higher loco-regional recurrence and standard preventive modalities reduce the risk. White women appear to have a higher recurrence probably related to risk factors (e.g. obesity) while the distribution of histological subtypes of DCIS, age at diagnosis, MIC, and treatment modalities did not significantly differ among diverse ethnic groups. Interestingly, a high rate of HER2 positive recurrences has been reported in our sample, suggesting that HER2 may represent a potential biomarker for DCIS at high risk of recurrence and therefore HER-2 targeted therapeutic interventions (e.g. vaccines, trastuzumab) can contribute to prevent it. Further analyses are needed to confirm the correlation between age/ethnicity and DCIS outcome. Better define the subgroup at worse prognosis could help to identify biomarkers predictive of recurrence or second tumors. Citation Format: Angela Toss, Adam Berger, Fran Guiles, Jocelyn Andrel Sendecki, Nicole L Simone, Rani P Anne, Tiffany P Avery, Rebecca J Jaslow, Juan P Palazzo, Melissa A Lazar, Theodore N Tsangaris, Massimo Cristofanilli. Clinical-pathological features and treatment modalities associated with disease recurrence in DCIS and micro-invasive carcinoma [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-13-05.

e11503 Background: The main goal in treating DCIS remains the prevention of ipsilateral recurrence and contralateral tumors. Known risk factors for recurrence include multifocal disease, tumor size, nuclear grade, presence of comedo necrosis, hormone receptor (HR) and HER-2 status and young age. Despite the similar distribution of molecular characteristics and treatments among ethnic groups, previous research reported that African Americans (AA) have worse outcomes. Methods: We identified 446 patients with DCIS (395) or microinvasive carcinoma (51), treated between 2008 and 2013, in the Thomas Jefferson University Tumor Registry. Associations between recurrence and demographic factors, histology, and treatment were assessed. Student’s t-test was used to compare age between recurrent and non-recurrent patients, Pearson’s Chi-squared test to test associations between recurrence variables with more than two categories, and Fisher’s Exact test for testing associations between recurrence and two-level categorical variables. Results: The median age was 59.5 years with a racial distribution of 65.7% white, 23.5% AA and 7.6% Asian. Moreover, 75.8% were ER positive, 66.8% PR positive and 20% HER2 positive. Mastectomy was performed in 26.7% of patients and 72.9% were treated with conservative surgery. AA and Asian patients were significantly more likely to undergo mastectomy. Adjuvant radiotherapy was utilized in 46.8% of women who underwent conservative surgery. Adjuvant chemotherapy was administered to 3.6% of women, preventive or adjuvant hormone therapy to 33.8%. To date, 22 patients developed a recurrence, 19 of which were in situ lesions. Only one of these patients had microinvasion in primary lesion. Conclusions: Our analysis confirms previously published results demonstrating that the histopathology of DCIS did not significantly differ among ethnic groups, even if AA patients were more likely HR positive and consequently were more frequently offered preventive endocrine therapy. The higher rate of mastectomy in AA, independent of patients’ preferences, may underlie a more aggressive disease biology and greater potential for multifocality requiring future evaluation of prognostic molecular biomarkers.

Aim: The primary aim in the management of DCIS is the prevention of ipsilateral and contralateral invasive tumors. African American (AA) women and younger age experience a higher incidence of disease recurrence and worse overall survival. The use of endocrine treatment significantly reduces recurrence rate and contralateral disease in hormone receptor positive (HR+) DCIS, but with significant costs and side effects. We analyzed the efficacy of tamoxifen (TAM) as preventive strategy and outcome according to age and ethnicity in DCIS patients.

Background and Aim: Hyperphosphatemia has been implicated in the development and treatment of various cancers. However, whether it can be used as a direct prognostic marker of colorectal cancer (CRC) has remained unexplored. Given new insights into the importance of hyperphosphatemia in CRC, we sought to evaluate the association of hyperphosphatemia with the clinical outcomes of this disease. Methods: In a retrospective analysis of a well-characterized clinic-based cohort with 1241 CRC patients, we assessed the association of postoperative hyperphosphatemia with patient overall survival. Results: Postoperative hyperphosphatemia measured within the first month after surgery was significantly associated with CRC survival. Compared to patients with a normal phosphate level, those with hyperphosphatemia exhibited a significant unfavorable overall survival with a hazard ratio (HR) of 1.84 (95% confidence interval [CI] 1.49-2.29, P = 2.6 x 10-8 (log-rank P = 1.2 x 10-7). Stratified analyses indicated the association was more pronounced in patients with colon (HR = 2.00, 95% CI 1.57-2.56, P = 3.17 x 10-8) but not rectal cancer (HR = 0.96, 95% CI 0.58-1.59, P = 0.889) (P interaction = 0.023), as well as in those not receiving chemotherapy (HR = 2.15, 95% CI 1.59-2.90, P = 6.2 x 10-7) but not in those receiving chemotherapy (HR = 1.30, 95% CI 0.92-1.82, P = 0.136) (P interaction = 0.012). Flexible parametric survival model demonstrated that the increased risk for death conferred by postoperative hyperphosphatemia persisted over 150 months after surgery. Conclusion: Our data indicated that postoperative hyperphosphatemia might be used as a prognostic marker of CRC patients after surgery. Since phosphate level is routinely tested in clinics, it may be incorporated into clinical models to predict CRC survival.

3621 Background: Cancer of the colon and rectum is the third most commonly occurring cancer, as well as the third leading cause of cancer deaths in American men and women. Colorectal cancer in younger patients is believed to have worse pathological features and prognosis than in older patients. The objective of this study was to assess pathological features and outcomes of CRC in patients less than age 50 using an institutional sample and comparing to the Surveillance, Epidemiology and End Results (SEER) database. Methods: Included in the study were a total of 4595 cases from the Tumor Registry at Thomas Jefferson University Hospital (TJUH) over a twenty year period from 1988 through 2007 and 290,338 cases from the Surveillance, Epidemiology and End Results (SEER) database from 1988 through 2004. Patients less than age 50 were compared to those age 50 and older. Results: Patients under age 50 with CRC presented with more advanced stage tumors in both data sets (<0.0001) , and had more poorly differentiated tumors than older patients (PTJUH=0.02754; PSEER<0.0001). Patients under 50 also had more mucinous/signet ring cell tumors with 12 percent to 8.1 percent in the TJUH data (p=0.002916) and 13.2 percent to 10.3 percent in the SEER data (p<0.0001), with younger males having the highest prevalence in both data sets. Younger patients had fewer proximal tumors than patients 50 and over, and a higher proportion of rectal tumors (p<0.001). Patients under age 50 were more likely to have positive nodes at all stages (PSEER <0.0001) relative to 50 and over, as well as more likely to develop peritoneal metastases (PTJUH=0.3507),, but less likely to have lung metastases PTJUH=0.05249) than older pts. Despite their poor pathologic features, patients under age 50 had better than or equal survival to those 50 and older. Conclusions: Colorectal cancer patients under age 50 presented with worse histological characteristics and metastasized much sooner, yet the younger patients had better than or equal survival to those ages 50 and older. Ongoing studies will assess differences in treatment and molecular features between younger and older colorectal cancer patients.

3631 Background: African Americans (AA) have a higher incidence and lower survival from colon and rectal cancer than Caucasian Americans (C). Disparities among AA and C have been attributed to multiple factors, including later stage at diagnosis, a higher proportion of poor histopathologic features, inadequate and unequal treatment, and socioeconomic factors. The multidisciplinary management setting provides similarity in management and treatment planning. The objective of this study was to assess pathologic features and survival of CRC in AA and C pts using a large institutional database and comparing national population-based data. Methods: We compiled data from 4,654 patients with colon and rectal cancer treated at Thomas Jefferson University Hospital from 1988-2010 and used Surveillance Epidemiology and End Results registry data from 1988-2004 to compare survival rates. Independent variables included age, racial background, site of primary tumor, differentiation, stage at presentation, recurrence-free survival, and overall survival rates for colon and rectal cancer and for each stage of the disease. We compared survival rates, using statistical modeling to account for disease characteristics between the two groups. Results: At diagnosis, AA pts presented with more advanced stage of disease, were more likely to have proximal disease (p<0.0001), had worse overall 5-year survival, and worse survival stage-by-stage than C pts. The odds ratio for risk of nodal involvement was greater for AA than C pts with lower T-tumors. AA pts were more likely to have less differentiated colon tumors, but more well-differentiated rectal tumors, younger age, and worse survival stage-by-stage than C pts. Although C pts were more likely to have rectal cancer (p<0.0001), they were less likely to have stage IV disease at presentation. Conclusions: AA pts with CRC are more likely to present at a younger age, with later stage, more proximal tumors, have higher nodal involvement with lower T-lesions, and less well differentiated tumors than C. Additional studies on biological features and molecular markers are ongoing and will be presented.

518 Background: African Americans (AA) have a higher incidence and lower survival rates from colon and rectal cancer than Caucasian Americans (C). This disparity has been attributed to many factors, including diagnosis at later stage, unfavorable histopathologic features, inadequate treatment, and socioeconomic factors. The multidisciplinary management setting ensures similarity in management and treatment planning. In this study, we assessed the pathological features and evaluated survival outcomes in patients with CRC in AA and CA using a large single institutional database. Methods: We compiled data from 3,826 patients with colon and rectal cancer treated at Thomas Jefferson University Hospital from 1988-2009 and used Surveillance Epidemiology and End Results registry data from 1988-2004 to compare survival rates. Independent variables included age, racial background, site of primary tumor, degree of differentiation, stage at presentation, recurrence-free survival and overall survival rates for colon and rectal cancer and for each stage of disease. We compared survival rates using statistical modeling to account for differences in patient and disease characteristics between the two groups. Results: At diagnosis, AA pts presented with more advanced stage of disease (p < 0.0001), were more likely to have proximal disease (p < 0.000000528), had worse overall 5-year survival, and worse survival stage-by-stage than C patients. Data also showed that the odds ratio for risk of nodal involvement was greater for AA pts than C pts with lower T tumors. AA pts were more likely to have less well differentiated colon tumors, but more well differentiated rectal tumors, younger age and worse survival stage-by stage than C pts. Although C pts were more likely to have rectal cancer (p < 0.0001), they were less likely to have stage IV disease at presentation. Conclusions: AA pts with CRC are more likely to present at a younger age with later stage, more proximal tumors, have higher nodal involvement with lower T lesions, and less well differentiated tumors than C. Additional studies on biological feature sand molecular markers are ongoing to and will be presented. No significant financial relationships to disclose.

Here, we investigated the possible predictive value of stromal caveolin-1 (Cav-1) as a candidate biomarker for clinical outcome in triple negative (TN) breast cancer patients. A cohort of 85 TN breast cancer patients was available, with the necessary annotation and nearly 12 years of follow-up data. Our primary outcome of interest in this study was overall survival. Interestingly, TN patients with high-levels of stromal Cav-1, had a good clinical outcome, with >50% of the patients remaining alive during the follow-up period. In contrast, the median survival for TN patients with moderate stromal Cav-1 staining was 33.5 months. Similarly, the median survival for TN patients with absent stromal Cav-1 staining was 25.7 months. A comparison of 5-year survival rates yields a similar pattern. TN patients with high stromal Cav-1 had a good 5-year survival rate, with 75.5% of the patients remaining alive. In contrast, TN patients with moderate or absent stromal Cav-1 levels had progressively worse 5-year survival rates, with 40% and 9.4% of the patients remaining alive. In contrast, in a parallel analysis, the levels of tumor epithelial Cav-1 had no prognostic significance. As such, the prognostic value of Cav-1 immunostaining in TN breast cancer patients is compartment-specific, and selective for an absence of Cav-1 staining in the stromal fibroblast compartment. A recursive-partitioning algorithm was used to assess which factors are most predictive of overall survival in TN breast cancer patients. In this analysis, we included tumor size, histologic grade, whether the patient received surgery, radiotherapy or chemotherapy, CK5/6, EGFR, p53 and Ki67 status, as well as the stromal Cav-1 score. This analysis indicated that stromal Cav-1 expression was the most important prognostic factor for overall survival in TN breast cancer. Virtually identical results were obtained with CK5/6 (+) and/or EGFR (+) TN breast cancer cases, demonstrating that a loss of stromal Cav-1 is also a strong prognostic factor for basal-like breast cancers. Our current findings may have important implications for the close monitoring and treatment stratification of TN and basal-like breast cancer patients.

PURPOSE:To report on the 15-year prostate cancer experience of our multidisciplinary genitourinary cancer clinic established in 1996 at the National Cancer Institute (NCI) -designated Jefferson Kimmel Cancer Center. Patients with genitourinary cancers were evaluated weekly by multiple specialists at a single site, and we focus on the 83% of patients with prostate cancer. To our knowledge, our multidisciplinary genitourinary cancer clinic is the longest continuously operating center of its kind at an NCI Cancer Center in the United States.METHODS:Data from Jefferson's Oncology Data Services were compared to SEER prostate cancer outcomes. Data on treatment changes in localized disease, patient satisfaction, and related parameters were also assessed.RESULTS:Ten-year survival data approach 100% in stage I and II prostate cancer. Ten-year data for stage III (T3 N0M0) and stage IV (T4 N0M0) disease show that our institutional survival rate exceeds SEER. There is a shift toward robotically assisted laparoscopic radical prostatectomy and a slight decrease in brachytherapy relative to external beam radiation therapy in localized disease. Patient satisfaction is high as measured by survey instruments.CONCLUSION:Our long-term experience suggests a benefit of the multidisciplinary clinic approach to prostate cancer, most pronounced for high-risk, locally advanced disease. A high level of satisfaction with this patient-centered model is seen. The multidisciplinary clinic approach to prostate cancer may enhance outcomes and possibly reduce treatment regret through a coordinated presentation of all therapeutic options. This clinic model serves as an interdisciplinary educational tool for patients, their families, and our trainees and supports clinical trial participation.

10551 Background: Breast carcinomas in African-American (AA) patients (pts) have poorer prognosis and higher likelihood of aggressive basal phenotype (triple negative for ER, PR, HER2) than those in Caucasian (C) patients (Carey et al, JAMA 2006, 295(21):2492; Morris et al, Breast Cancer Res Treat 2006, abstr 3055). We have additionally examined biomarker expression by phenotype in AA pts in our registry to further explain more aggressive behavior in this population. Methods: Stage, grade, ER, PR, Ki-67, HER2, and p53 expressions were compiled for breast carcinomas in 2,230 AA and C pts diagnosed between 1995–2004. Immunohistochemical markers were assayed using antibodies to the above proteins on paraffin-embedded formalin-fixed tissue. Differences in expression were analyzed by Chi- squared and Wilcoxon tests, and survival by Kaplan-Meier estimates. Results: AA pts have higher propensity for basal phenotype breast cancers (20.8% vs 10.4%, p<0.001) and lower propensity for Luminal A/B (ER+/PR+-/HER2-) phenotype (44.2% vs. 54.1%, p<0.001) as compared with C pts. Higher ki-67 proliferation index was found in AA pts (86.4% vs 78.8% in basal, p=0.3423; 37.1% vs. 26.7% in Luminal A/B p=0.0233) as compared with C pts. p53-positivity was higher in AA and C pts in all cases (p=0.0158), higher in AA pts with basal phenotype (p=0.2597), but identical in AA and C pts with luminal phenotypes (p=0.881). Survival was similar in basal phenotypes between races in all cases stage for stage, and controlled for ki-67 and p53 status, with a trend toward poorer survival among luminal phenotypes between races. Conclusions: AA pts have higher propensity for basal phenotype breast cancers than C pts, with higher ki-67 expression in both basal and luminal phenotypes, and higher p53 expression in basal phenotype, but these do not correlate with significant differences in survival by phenotype between races. As neither ki-67 index nor p53 expression can therefore solely explain differences in survival rates seen between races, molecular array studies between races and matched by phenotype are proposed. [Table: see text]

BACKGROUND. Breast carcinomas in African-American patients appear to be more aggressive than in Caucasian patients due to multifactorial differences.METHODS. The authors compiled pathology data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database regarding stage, histologic grade, and estrogen receptor (ER) expression in breast carcinomas diagnosed in 197,274 African-American and Caucasian patients between 1990 and 2000, and the same information, along with nuclear grade, Ki-67, c-erb-B2, and p53 expression, in 2230 African-American and Caucasian patients diagnosed at Thomas Jefferson University Hospital between 1995 and 2002. Immunohistochemical markers were assayed in paraffin- embedded, formalin-fixed tissue stained with hematoxylin and eosin using antibodies to these proteins, with differences in expression analyzed by the chisquare test.RESULTS. in both databases, more African-American patients presented with advanced stage tumors and higher histologic (P <.001) and nuclear grade (P <.001) than Caucasian patients. African-American patients had less ER positivity (51.9% vs 63.1%; P <.001) but significantly higher Ki-67 (42.4% vs 28.7%; P <.001) and p53 expression (19.4% vs 13.1%; P <.05) than Caucasian patients with all stages of disease. In addition, the basal or "triple -negative" breast cancer phenotype was more common in African-American patients than in Caucasian patients (20.8% vs 10.4%; P <.0001), and was associated with higher histologic and nuclear grade (P <.0001).CONCLUSIONS. African-American patients with breast carcinomas are more likely than Caucasian patients to present with tumors that are of a later stage and higher grade, with higher Ki-67 expression and more ER negativity, thereby highlighting a greater need for early screening among African-American women. Molecular studies that may explain these differences, and correlations with survival, have been proposed to identify therapeutic targets.