Robert L Dewitty

Howard University, Washington, West Virginia, United States

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Publications (19)102.72 Total impact

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    ABSTRACT: Fascin, an actin bundling protein, plays a critical role in cell motility due to formation of actin rich protrusions called filopodia, important in cell migration, invasion and metastatic spread. Fascin overexpression has been associated with epithelial to mesenchymal transition and correlates with progression and unfavourable prognosis in breast carcinoma. To evaluate fascin expression by immunohistochemistry and correlate the expression pattern with clinicopathological parameters in breast cancer in African-American (AA) women, in whom triple negative breast cancer (TNBC), an aggressive subtype, is more prevalent. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of tumour tissue from primary breast carcinomas in 202 AA women. Immunohistochemical detection of fascin was correlated with four major subtypes of breast carcinoma (luminal A, luminal B, human epidermal growth factor receptor 2 and triple negative (TN)) and other clinicopathological factors, including age, grade, tumour size, stage, regional lymph node status and survival. We observed a significant association between fascin expression and TN subtype, oestrogen receptor (ER) negativity, progesterone receptor (PR) negativity, Elston-Nottingham (EN) grade 3 and decreased overall survival. There was also a significant association between expression of CK 5/6, a marker of basal-like phenotype, and fascin expression. These results suggest that fascin is a marker for TN subtype having a basal-like phenotype and decreased overall survival. Fascin may represent a target for therapy in TNBC in AA women.
    Journal of clinical pathology 08/2013; · 2.43 Impact Factor
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    ABSTRACT: Due to increased awareness of breast cancer resulting in early detection, there is a decreased incidence nationwide of late-stage breast cancer, including that which presents with skin involvement (T4b). A retrospective analysis of a 10-month period from August 2007 to May 2008 at Howard University Hospital (HUH), Washington, DC, revealed 12 patients diagnosed with T4b breast cancer and compared to similarly staged patients in the Surveillance, Epidemiology, and End Results (SEER) database. Finally, a logistic regression for the likelihood of T4b diagnosis was performed patients in the SEER database. HUH patients with T4b tumors were more likely than SEER patients to present with predictors of poor clinical outcome, including high-grade histology (100% vs 59.4%, p = .04) and estrogen receptor- (75% vs 30.3%, p = .001) and progesterone receptor- negative (91.7% vs 43.9%, p = .001) status. Conversely, HUH patients were younger (57.8 y vs 66.3 y, p = .03) and had smaller tumors (11.1 cm vs 28.2 cm, p = .02) than SEER patients with similarly staged tumors. Older patients (OR, 2.36; 95% CI, 1.50-2.00; p < .001; 60-80 y), African American patients (OR, 1.63; 95% CI, 1.26-2.11; p < .001), and patients with high-grade (OR, 5.51; 95% CI, 3.88-6.52; p < .001) tumors were more likely to be diagnosed with T4b tumors, whereas patients who lived in an area with increased median household income (OR, 0.99; 95% CI, 0.99-0.99; p = .001) were less likely to be diagnosed with a T4b lesion. While much research has focused on the socioeconomic causes for the development of T4b tumors, both patient and tumor biologic conditions cannot be eliminated as causative agents.
    Journal of the National Medical Association 08/2011; 103(8):757-61. · 0.91 Impact Factor
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    ABSTRACT: To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN. Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1-T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years. Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4-97.2%). No single gene or combination of study genes was predictive of recurrence. The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.
    Annals of Surgical Oncology 10/2010; 17 Suppl 3:312-20. · 4.12 Impact Factor
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    ABSTRACT: The Gail model has been used to predict invasive breast cancer risk in women using risk factors of age, age at menarche, age at first live birth, number of first-degree relatives with breast cancer, and number of previous benign breast biopsies. However, this model underestimates breast cancer risk in African-American women. The Contraceptive and Reproductive Experience (CARE) model has been developed to replace the Gail model in predicting breast cancer risk in African-American women. In a sample of 883 women who participated in the breast cancer screening program at Howard University Cancer Center, we compared the breast cancer risk estimates from the Gail model and the CARE model. The mean 5-year breast cancer risk was 0.88% (Range: 0.18-6.60%) for the Gail model and 1.29% (Range: 0.20-4.50%) for the CARE model. Using the usual cutoff-point of 1.67% or above for elevated risk, there is a significant difference in the proportion of women with elevated breast cancer risk between the Gail and the CARE models (McNemar's test, p < 0.0001). For both models, there was a significant mean risk difference between those with and without a family history of breast cancer (Wilcoxon rank-sum test, p < 0.0001). Our results confirm the need for validation of the Gail model in African-Americans and diversity in research. Although these findings are not perfect and perhaps not definitive, they are additive in the discussions during counseling and risk assessment in African-Americans. Furthermore, these findings will be complemented by new technologies such as genomics in refining our ability to assess risk.
    The Breast Journal 09/2009; 15 Suppl 1:S72-5. · 1.83 Impact Factor
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    ABSTRACT: In the current study we tested if highest incidence of benign as well as cancer growths in breast tissue is due to constitutive molecular composition of this tissue. To delineate the molecular basis, we compared the expression of nine functional gene modules (total 578 genes) that regulate major positive growth and negative inhibitory signals in normal breast with two other reproductive tissues, ovary and uterus. We present data to demonstrate that breast tissues constitutively have very highly elevated levels of several growth promoting molecules and diminished levels of inhibitory molecules which may, in part, contribute for highest incidence of tumor growths in this tissue.
    FEBS letters 09/2009; 583(18):3069-75. · 3.54 Impact Factor
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    ABSTRACT: With the current classification of breast carcinoma into molecular subtypes with distinct prognosis and response to therapy, we sort to assess the clinical significance of p53 and bcl-2 coexpression phenotypes in invasive breast tumors and correlate this to the different molecular breast cancer subtypes in African-American women. We performed a retrospective analysis of data on p53 and bcl-2 expression. Results were correlated to molecular breast cancer subtypes, and clinicopathologic variables of prognostic significance. Our study sample included all African-American women diagnosed with breast cancer from 1998 to 2005. Twenty-seven (27.6%) per cent of cases in our study sample over-expressed p53, whereas 69.3 per cent over-expressed bcl-2 protein. A significant inverse correlation was observed between expression of p53 and bcl-2. Combined analysis of p53 and bcl-2 showed that 53.2 per cent of the tumors displayed p53(-)bcl-2(+) phenotype which was significantly associated with the luminal A subtype, whereas 11.6 per cent displayed the p53(+)bcl-2(-) phenotype which was significantly associated with the basal cell-like and Her-2/neu. Neither p53 expression nor bcl-2 expression individually or in combination were of independent prognostic significance. p53(+)bcl-2(-) phenotype is significantly correlated with the basal cell-like subtype and may be associated with the biologic aggressiveness of this cohort of molecular breast cancer.
    The American surgeon 09/2009; 75(9):776-84; discussion 784. · 0.92 Impact Factor
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    ABSTRACT: Age, gender, and ethnic group-related differences influence the outcome of gastric cancer. Our aim was to analyze the trends and association of clinicopathologic characteristics and prognostic factors of gastric cancer in black patients over a period of 28 y. A retrospective analysis of all black patients treated for gastric cancer from 1979 to 2007 at Howard University Teaching Hospital. This period was divided into two time frames, 1979-1993 and 1994-2007. Of 286 patients in our study, there were 160 (55.9%) males versus 126 (44.1%) females. For the period 1979-1993, there were a total of 169 (59.1%) patients versus 117 (40.9%) for 1994-2007. A significant increase in the incidence of cardia/fundus tumors and stage IV tumors was noted between the two periods (P<0.02, P<0.004), 8.9% versus 12% and 71.4% versus 50.8%. The median survival time for the period 1979-1993 was 30.5 mo versus 39.2 mo for 1994-2007. The median survival time for males was 35.7 mo versus 34.9 mo for females. Significant independent predictors of a shorter gastric cancer-specific survival include tumor stage IV (HR 8.4 95% CI 2.0-35.0, P<0.003), female gender (HR 2.3 95% CI 1.0-4.9, P<0.02). Increased incidence of cardia/fundus tumors and stage IV disease may contribute to the sustained higher gastric cancer-specific mortality observed amongst black patients. Female gender emerged as an independent predictor of a shorter survival time.
    Journal of Surgical Research 05/2009; 156(2):325-32. · 2.02 Impact Factor
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    ABSTRACT: To analyze whether the local-regional surgical treatments (breast-conserving therapy, mastectomy) resulted in different overall survival, distant metastasis-free survival, and locoregional recurrence-free survival rates for the various molecular breast cancer subtypes. Molecular gene expression profiling has been proposed as a new classification and prognostication system for breast cancer. Current recommendation for local-regional treatment of breast cancer is based on traditional clinicopathologic variables. Retrospective analysis of 372 breast cancer cases with assessable immunohistochemical data for ER, PR, and Her-2/neu receptor status, diagnosed from 1998 to 2005. Molecular subtypes analyzed were luminal A, luminal B, basal like, and Her-2/neu. No substantial difference was noted in overall survival, and locoregional recurrence rate between the local-regional treatment modalities as a function of the molecular breast cancer subtypes. The basal cell-like subtype was an independent predictor of a poorer overall survival (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.28-4.97, P < 0.01) and a shorter distant metastasis-free survival time (HR = 3.61, 95% CI 1.27-10.2, P < 0.01), and showed a tendency toward statistical significance as an independent predictor of locoregional recurrence (HR = 3.57, 95% CI 0.93-13.6, P = 0.06). The basal cell-like subtype is associated with a worse prognosis, a higher incidence of distant metastasis, and may be more prone to local recurrence when managed with breast-conserving therapy.
    Annals of Surgery 04/2008; 247(3):463-9. · 6.33 Impact Factor
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    ABSTRACT: It has been reported that approximately a million women are diagnosed with benign breast lesions that include ductal hyperplasias per year in the United States. Recent studies that followed women with benign lesions have established that about 8% to 9% of them will subsequently develop invasive breast cancer (IBC). However, currently, there are no means of identifying a subclass of "true precancerous tissues" in women with ductal hyperplasias who will subsequently develop cancer. The purpose of this study is to investigate whether expression of hyaluronoglucosaminidase 1 (HYAL1), a known tumor promoter, in hyperplastic tissues identifies a "true precancerous stage" and predicts subsequent IBC development. A retrospective study was conducted with archival benign tissues of various histologic types and clinical information on development/nondevelopment of IBC. The control group was hyperplastic tissues from women who had no prior history of IBC and did not develop cancer in 5 to 7 years after diagnosis (n = 81). The test group was hyperplastic tissues from patients who developed cancer (n = 82). HYAL1 expression was studied by immunohistochemistry, and the results were statistically analyzed for significant association to develop cancer (P value), specificity, sensitivity, positive predictive value, and negative predictive value. Statistical analysis of HYAL1 expression data showed very highly significant association between its expression and subsequent cancer development (P = 0) and very high sensitivity (0.83), specificity (0.84), positive predictive value (0.84), and negative predictive value (0.83). The expression of HYAL1 in ductal hyperplastic tissues is a strong predictor of subsequent development of IBC; therefore, it can be applied as a diagnostic marker either singly or in combination with other marker(s) to screen benign tissues to predict subsequent development of IBC. Detection at the precancerous stage and treatment could drastically cut down breast cancer incidence and deaths from it.
    Clinical Cancer Research 03/2008; 14(4):1274-80. · 7.84 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the prognostic significance of the basal cell-like molecular breast cancer subtype with respect to locoregional recurrence and distant metastasis in African American women treated for breast cancer. A retrospective analysis was performed of the tumor registry database for all African American women diagnosed and treated for breast cancer from 1998 to 2005 who had assessable data for all 3 markers: estrogen, progesterone, and Her-2/neu. A total of 372 patients were included in our study sample. Of these, 22 (6.1%) had locoregional recurrence, 35 (9.8%) had distant metastasis, and 301 (84.1%) had no evidence of breast tumor recurrence. The median follow-up time was 36 months. Compared with the other molecular subtypes the basal cell-like subtype showed a statistically significant association to distant metastasis: 15 (42.9%) vs 13 (37.1%), 4 (11.4%), and 3 (8.6%) (P < .001), respectively, for luminal A, Her-2/neu, and luminal B subtypes. The basal cell-like subtype was an independent predictor of distant metastasis (odds ratio, 5.8; 95% confidence interval, 1.5-22.0, P = .009). The molecular subtypes showed no statistically significant difference with respect to locoregional treatment administered and tumor stage at time of diagnosis. The basal cell-like molecular breast cancer subtype is an independent predictor of distant metastasis in African American women.
    American journal of surgery 02/2008; 195(2):153-8. · 2.36 Impact Factor
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    ABSTRACT: GPR30 is a cell surface estrogen receptor that has been shown to mediate a number of non-genomic rapid effects of estrogen and appear to balance the signaling of estrogen and growth factors. In addition, progestins appear to use GPR30 for their actions. Therefore, GPR30 could play a critical role in hormonal regulation of breast epithelial cell integrity. Deregulation of the events mediated by GPR30 could contribute to tumorigenesis. To understand the role of GPR30 in the deregulation of estrogen signaling processes during breast carcinogenesis, we have undertaken this study to investigate its expression at mRNA levels in tumor tissues and their matched normal tissues. We compared its expression at mRNA levels by RT quantitative real-time PCR relative to GAPDH in ERα"-positive (n = 54) and ERα"-negative (n = 45) breast cancer tissues to their matched normal tissues. We report here, for the first time, that GPR30 mRNA levels were significantly down-regulated in cancer tissues in comparison with their matched normal tissues (p < 0.0001 by two sided paired t-test). The GPR30 expression levels were significantly lower in tumor tissues from patients (n = 29) who had lymph node metastasis in comparison with tumors from patients (n = 53) who were negative for lymph node metastasis (two sample t-test, p < 0.02), but no association was found with ERα, PR and other tumor characteristics. Down-regulation of GPR30 could contribute to breast tumorigenesis and lymph node metastasis.
    Breast cancer 01/2008; 1:65-78.
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    ABSTRACT: Breast cancer is currently regarded as a heterogeneous disease classified into various molecular subtypes using gene expression analysis. These molecular subtypes include: basal cell-like, Her-2/neu, luminal A, and luminal B. To analyze the prevalence and clinicopathologic associations for molecular breast cancer subtypes in premenopausal and postmenopausal African-American women. A retrospective analysis of all African-American women diagnosed with breast cancer from 1998 to 2005, who had assessable data for ER, PR, and Her-2/neu status. Molecular subtype classification was done based on immunohistochemical surrogates for ER, PR, and Her-2/neu status obtained from Howard University tumor registry for each patient. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and Her-2/neu (ER-, PR-, and HER2+). We analyzed the prevalence of molecular breast cancer subtypes in a population of African-American women and determined their associations with patient demographics and clinicopathologic variables: node status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival. The luminal A subtype was the most prevalent in our study sample (55.4%) compared with (11.8%) luminal B, (21.2%) basal cell-like, and (11.6%) Her-2/neu subtypes. The molecular subtypes did not differ by menopausal status. However, when stratified into age-specific groups, the basal cell-like subtype (57.1%) was the most prevalent in the age group <35 y compared with luminal A, luminal B, and Her-2/neu subtypes at 25.0%, 14.3%, and 3.6%, respectively. The basal cell-like subtype also showed an age-specific bimodal distribution with a peak in the <35 y and 51 to 65 y age groups. The basal cell-like and the Her-2/neu subtypes showed an increased association with clinicopathologic variables portending a more aggressive clinical course when compared with luminal A subtype. A paradoxical inverse relationship between the expression of p53 and Bcl-2 protooncoprotein was noted in the molecular subtypes. Breast cancer-specific survival differed significantly among the molecular subtypes (P < 0.04), with the basal cell-like and Her-2/neu subtypes having the poorest outcome. The high prevalence of the basal cell-like subtype in the young premenopausal African-American women aged <35 y could be a contributory factor to the poorer prognosis of breast cancer observed in this cohort of patients.
    Journal of Surgical Research 11/2007; 143(1):109-18. · 2.02 Impact Factor
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    ABSTRACT: Breast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women. A retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998-2005, was performed. The luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01). The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31). The high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.
    Annals of Surgical Oncology 11/2007; 14(10):2994-3003. · 4.12 Impact Factor
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    ABSTRACT: Epidemiologic studies have established that women with prior atypical ductal hyperplastic (ADH) lesions have a 5-fold increased risk of developing invasive breast cancer (IBC). However, there is currently no means of identifying a subclass of ADH from women who will most likely develop cancer. The purpose of this study is to investigate whether elevated expression of carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in ADH tissues is associated with the development of IBC. A retrospective study was conducted with archival ADH tissues and clinical information on the development/nondevelopment of IBC. The control group was ADH from patients who had no prior history of IBC and did not develop cancer within 5 years after the diagnosis of ADH (n = 44). The test group was ADH from patients who either developed cancer concurrently or subsequently after diagnosis (ADHC; n = 44). The expression of CEACAM6 was studied by immunohistochemistry and the results were statistically analyzed for significant association to develop cancer (P value), specificity, sensitivity, positive predictive value, and negative predictive value. Of the 44 control ADH tissues from patients with no history of cancer, 9 were positive for CEACAM6. Among the ADHC tissues, 40 of 44 samples were positive. Statistical analysis of CEACAM6 expression data showed a significant association between its expression and cancer development, high sensitivity, specificity, positive predictive value, and negative predictive value. The expression of CEACAM6 in ADH lesions is strongly associated with the development of IBC, therefore, it can be applied as a diagnostic marker either singly or in combination with other marker(s) to predict IBC development in women with ADH lesions. It could also be a potential molecular therapeutic target for preventing IBC.
    Clinical Cancer Research 09/2006; 12(15):4773-83. · 7.84 Impact Factor
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    ABSTRACT: Breast cancer is the second leading cause of cancer death for women in the United States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000 cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of IBC in the US. Yet there is presently no molecular marker that can be used to detect a precancerous state or identify which premalignant lesions will develop into invasive breast cancer. Here we report the gene expression analysis of atypical ductal hyperplastic tissues from patients with and without a history of breast cancer. We identify MMP-1 as a candidate marker that may be useful for identification of breast lesions that can develop into cancer.
    Nature Medicine 06/2005; 11(5):481-3. · 22.86 Impact Factor
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    ABSTRACT: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and nonsentinel ALN has not been established. Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.
    Annals of Surgery 06/2004; 239(6):828-37; discussion 837-40. · 6.33 Impact Factor
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    ABSTRACT: African Americans have the highest cancer mortality rates and poorest survival and are more often uninsured and underinsured compared with other ethnic groups. Minority participation in clinical trials has traditionally been low, with reports ranging from 3% to 20%. The present study systematically assesses 235 consecutively diagnosed African American cancer patients regarding recruitment onto cancer treatment clinical trials at Howard University Cancer Center between January 1, 2001, and December 31, 2002. Our intent is to determine the rate-limiting factors associated with enrolling African Americans onto clinical trials at a historically black medical institution. Two hundred thirty-five consecutively diagnosed African American cancer patients were assessed for participation in clinical trials at Howard University Hospital and Cancer Center. The study population comprised 165 women and 70 men. The overall eligibility rate was 8.5% (20 of 235 patients); however, among those eligible, the enrollment rate (ie, enrollment among the eligible population) was 60.0% (12 of 20 patients). Comorbidities rendered 17.1% of the patient population ineligible for the trials. Advanced disease stage, associated with poor performance status, premature death, and short life expectancy, made an additional 10% of the patient population ineligible. Respiratory failure, HIV positivity, and anemia accounted for 37.8% of the comorbidities in this population. Cardiovascular diseases and renal insufficiency represented 16.2% of the comorbidities. It was evident that study design exclusion and inclusion criteria rendered the majority of the study population ineligible. Among African Americans, comorbidity is a major issue that warrants considerable attention.
    Journal of Clinical Oncology 03/2004; 22(4):730-4. · 18.04 Impact Factor
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    ABSTRACT: Incidence of breast cancer (BC) varies among ethnic groups, with higher rates in white than in African-American women. Until now, most epidemiological and genetic studies have been carried out in white women. To investigate whether interactions between genetic and reproductive risk factors may explain part of the ethnic disparity in BC incidence, a genetic epidemiology study was conducted, between 1989 and 1994, at the Howard University Cancer Center (Washington, DC), which led to the recruitment of 245 African-American families. Segregation analysis of BC was performed by use of the class D regressive logistic model that allows for censored data to account for a variable age of onset of disease, as implemented in the REGRESS program. Segregation analysis of BC was consistent with a putative dominant gene effect (P < 0.000001) and residual sister-dependence (P < 0.0001). This putative gene was found to interact significantly with age at menarche (P = 0.048), and an interaction with a history of spontaneous abortions was suggested (P = 0.08). A late age at menarche increased BC risk in gene carriers but had a protective effect in non-gene carriers. A history of spontaneous abortions had a protective effect in gene carriers and increased BC risk in non-gene carriers. Our findings agree partially with a similar analysis of French families showing a significant gene x parity interaction and a suggestive gene x age at menarche interaction. Investigating gene x risk factor interactions in different populations may have important implications for further biological investigations and for BC risk assessment.
    Genetic Epidemiology 04/2002; 22(4):285-97. · 4.02 Impact Factor
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    ABSTRACT: Several cancer surveys have shown that African-American women (AAW) develop highly aggressive breast tumors and experience about three times higher mortality rates compared with other populations. Generally, breast tumors in AAW are poorly differentiated or undifferentiated and exhibit increased frequency of nuclear atypia, higher mitotic activity, higher S-phase fraction, and tumor necrosis. The molecular factors responsible for these tumor characteristics are mostly unknown. To explore whether the aggressive tumor biology observed in AAW is related to distinct alterations in estrogen receptor (ER) isoforms, the relative expression levels of four functionally active ER isoform mRNAs, ERalpha wild type, ERbeta wild type, ERalpha exon 3delta, and ERalpha exon 5delta, were measured by reverse transcriptase-polymerase chain reaction analysis in 18 immunohistochemically ERalpha positive tumors and in 6 ERalpha negative tumors and their matched normal tissues. In the tumors of AAW, the protective ERbeta isoform was decreased significantly compared with matched normal tissues (paired t test; n = 24 patients; P = 0.0018). In addition, both the constitutively active ERalpha exon 5delta and the dominant negative ERalpha exon 3delta mRNA levels were elevated in tumor tissues compared with matched normal tissues (paired t tests; n = 24 patients; P = 0.0002 and P = 0.024, respectively). The data presented here show for the first time that functionally active ER isoform profiles in the breast tumors of AAW are different from those in Caucasian women. The tumors in AAW are characterized by decreased levels of the protective ERbeta isoform and elevated levels of the constitutively active ERalpha exon 5delta isoform. Variations in estrogen-mediated signaling because of the alterations in these two ER isoforms may account in part for differences in tumor biology between AAW and Caucasian women.
    Cancer 03/2002; 94(3):615-23. · 5.20 Impact Factor

Publication Stats

387 Citations
102.72 Total Impact Points

Institutions

  • 2004–2010
    • Howard University
      • • Department of Surgery
      • • Cancer Center
      Washington, West Virginia, United States
  • 2002–2009
    • Howard University Hospital
      Washington, Washington, D.C., United States