Tammey Naab

Molecular Breast Cancer Subtypes in Premenopausal African-American Women, Tumor Biologic Factors and Clinical Outcome

IntroductionBreast 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.MethodsA 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.ResultsThe 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).ConclusionThe 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.

Treatment and Survival Outcome for Molecular Breast Cancer Subtypes in Black Women

Objective: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. Summary Background Data: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. Methods: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. Results: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). Conclusions: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.

Strong association of fascin expression with triple negative breast cancer and basal-like phenotype in African-American women

Background 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. Objective 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. Methods 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. Results 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. Conclusion 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.

Risk of prostate cancer in African-American men: Evidence of mixed effects of dietary quercetin by serum vitamin D status

African‐American (AA) men experience higher rates of prostate cancer (PCa) and vitamin D (vitD) deficiency than white men. VitD is promoted for PCa prevention, but there is conflicting data on the association between vitD and PCa. We examined the association between serum vitD and dietary quercetin and their interaction with PCa risk in AA men.

Fatal Disseminated Fusarium Infection in a Human Immunodeficiency Virus Positive Patient

Systemic mycotic infections have been increasing in incidence in immunocompromised patients. Although yeasts are most often isolated, opportunistic fungal infections may also be caused by filamentous fungi, including Aspergillus and Fusarium. Like Aspergillus, Fusarium is angioinvasive with an ability to disseminate widely. Disseminated fusariosis is most commonly linked to prolonged neutropenia. Disseminated infections due to Fusarium are rare in Human Immunodeficiency Virus (HIV) positive patients but have been reported in HIV positive patients with neutropenia and lymphoma. We describe an HIV positive patient without neutropenia, skin lesions, or concomitant malignancy, who developed fatal disseminated infection with possible endocarditis due to Fusarium solani. Early identification of Fusarium is important because of its high level of resistance to several antifungal drugs, with response often requiring combination therapy.

Testicular plasmacytoma in a patient with the acquired immunodeficiency syndrome

Clinical, laboratory, and pathologic findings from a case of primary extramedullary plasmacytoma of the testis and sinuses in a patient with acquired immunodeficiency syndrome (AIDS) are presented. To our knowledge this is the first case in the English literature of a primary testicular plasmacytoma in an HIV-infected patient. The findings in this report and those of others confirm the difference in the pattern of plasma cell tumor (PCT) presentation in patients infected with AIDS from those in non-infected individuals, suggesting that these tumors should be considered in the differential diagnosis of AIDS-associated malignancies.

Loss of PTEN in High Grade Advanced Stage Triple Negative Breast Ductal Cancers in African American Women

INTRODUCTION PTEN is a tumor suppressor gene that inhibits cell proliferation by inhibiting the phosphoinositide 3-kinase (PI3 K) signaling pathway. The significance of PTEN mutations resulting in variable PTEN expression and their impact on prognosis of breast cancer is not well established. The objective of our study was to correlate the immunohistochemical expression of PTEN in the four major subtypes of breast carcinoma (Luminal A, Luminal B, HER2 positive, and Triple Negative) in a population of 202 African-American (AA) females with other clinicopathological factors. MATERIALS AND METHODS Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 African-American females. Five micrometer sections were stained with a mouse monoclonal antibody against PTEN. The sections were evaluated for the intensity of cytoplasmic and nuclear reactivity. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). RESULTS Loss of PTEN expression was associated with ER negative (p = 0.021), PR negative (p = 0.024) and triple negative (p = 0.0024) breast ductal cancers. It was marginally associated with distant metastasis (p = 0.074). There was no association between PTEN loss and recurrence-free survival or overall survival. CONCLUSION In our study, a statistically significant association between PTEN loss and the triple negative breast cancers (TNBC) was found in AA women. PTEN inhibits PI3 K resulting in decreased activation of downstream effector, mammalian target of rapamycin (mTOR). Loss of PTEN results in cell proliferation through activation of mTOR. Targeted therapy with mTOR inhibitors might be useful in the treatment of TNBC.

Expanding Hospital Human Immunodeficiency Virus Testing in the Bronx, New York and Washington, District of Columbia: Results from the HPTN 065 Study

Background Human immunodeficiency virus (HIV) testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. Methods To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington, District of Columbia (DC) undertook efforts to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. Results From 1 February 2011 to 31 January 2014, HIV tests were conducted during 6.5% of 1621016 ED visits and 13.0% of 361745 inpatient admissions in Bronx hospitals and 13.8% of 729172 ED visits and 22.0% of 150655 inpatient admissions in DC. From year 1 to year 3, testing was stable in the Bronx (ED visits: 6.6% to 6.9%; inpatient admissions: 13.0% to 13.6%), but increased in DC (ED visits: 11.9% to 15.8%; inpatient admissions: 19.0% to 23.9%). In the Bronx, 0.4% (408) of ED HIV tests were positive and 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive and 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive and 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient tests were positive and 0.7% (189) were new diagnoses. Conclusions Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive.

Next Generation Sequencing Reveals High Prevalence of BRCA1 and BRCA2 Variants of Unknown Significance in Early-Onset Breast Cancer in African American Women

BACKGROUND Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. METHODS In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer. To improve the characterization of the BRCA1 and BRCA2 variants, bioinformatics tools were utilized to predict the potential function of each of the variants. RESULTS Using next generation sequencing methods and in silico analysis of variants, a total of 197 BRCA1 and 266 BRCA2 variants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; BRCA2 Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemiological approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14). CONCLUSIONS Knowing a patients BRCA mutation status is important for prevention and treatment decision-making. Improving the characterization of mutations will lead to better management, treatment, and BCa prevention efforts in African Americans who are disproportionately affected with aggressive BCa and may inform future precision medicine genomic-based clinical studies.

Scrotal mass and unilateral lung masses with pleural effusion mimicking metastatic testicular malignancy: an unusual presentation of sarcoidosis

Involvement of the genitourinary tract by sarcoidosis may present with a scrotal mass, mimicking infection or malignancy. Sarcoidosis is a systemic granulomatous disease that affects patients of both sexes worldwide. Sarcoidosis of the genitourinary tract is rare. We describe a case of a 33-year-old African–American man who presents with a scrotal mass, mediastinal mass, unilateral lung masses and pleural effusion mimicking testicular malignancy with pulmonary metastases. The histopathological examination of the right testis and lung biopsy revealed granulomatous inflammation consistent with sarcoidosis. Genitourinary sarcoidosis must be a diagnostic consideration, especially in an African-American patient with a scrotal mass. There is a possible association between sarcoidosis and testicular malignancy; hence, underlying malignancy should always be ruled out. Serum tumour markers, ACE, a biopsy of the accessible tissue and intraoperative frozen section analysis aid in establishing the diagnosis of sarcoidosis and leading to appropriate management.