MYC amplification in subtypes of breast cancers in African American women

BACKGROUND: MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics. METHODS: We analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification. Utilizing immune histochemical analysis estrogen receptor (ER), progesterone receptor (PR), and (HER2/neu), were assessed. Cases were Luminal A (ER or PR+, Ki-67 \u3c 14%), Luminal B (ER or PR+, Ki-67 = \u3e 14% or ER or PR+ HER2+), HER2 (ER-, PR-, HER2+), and Triple Negative (ER-, PR-, HER2-) with basal-like phenotype. The relationship between MYC amplification and prognostic clinico-pathological characteristics was determined using chi square and logistic regression modeling. RESULTS: Sixty-five (97%) of the tumors showed MYC gene amplification (MYC: CEP8 \u3e 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p \u3c 0.0001), stage (p \u3c 0.001), metastasis (p \u3c 0.001), and positive lymph node status (p = 0.039). MYC amplification was associated with HER2 status (p = 0.01) and tumor size (p = 0.01). High MYC amplification was seen in grade III carcinomas (MYC: CEP8 = 2.42), pre-menopausal women (MYC: CEP8 = 2.49), PR-negative status (MYC: CEP8 = 2.42), and ER-positive status (MYC: CEP8 = 2.4). CONCLUSIONS: HER2 positive BCas in AA women are likely to exhibit MYC amplification. High amplification ratios suggest that MYC drives HER2 amplification, especially in HER2 positive, Luminal B, and subtypes of BCa

Beyond Triple-Negative: High Prevalence of Quadruple-Negative Breast Cancer in African Americans

Quadruple-negative breast cancer (QNBC) is a triple-negative breast cancer (TNBC) subtype that lacks expression of the androgen (AR) receptor. Few studies have focused on this highly aggressive breast cancer, portending worse survival rates. We aimed to determine the following: (1) QNBC’s molecular and clinical characteristics and compare them with other subtypes and (2) QNBC’s association with clinicopathological factors and prognostic markers. We performed immunohistochemical evaluations of ARs on tissue tumor microarrays from FFPE tumor blocks of invasive ductal breast carcinomas in 202 African American women. Univariate analysis was performed using the chi-square test, with survival rates calculated using Kaplan–Meier curves. Overall, 75.8% of TNBCs were AR-negative. Compared to the luminal subtypes, TNBC and QNBC tumors were likely to be a higher grade (p p < 0.001). They also expressed increasing mean levels of proteins involved in invasion, such as CD44, fascin, and vimentin, as well as decreasing the expression of proteins involved in mammary differentiation, such as GATA3 and mammaglobin. We found no association between QNBC and stage, recurrence-free survival, or overall survival rates. The high prevalence of TNBC AR-negativity in these women could explain observed worse outcomes, supporting the existence of the unique QNBC subtype

Corrigendum to “Annexin 2 protein expression is associated with breast cancer subtypes in African American women” [Heliyon Volume 6, Issue 2, February 2020, e03241](S2405844020300864)(10.1016/j.heliyon.2020.e03241)

In the original published version of this article, the figure captions for figure 3 and 4 were missing the final word: (B). The authors apologise for this error. Both the HTML and PDF versions of the article have been updated to correct the error

Annexin 2 protein expression is associated with breast cancer subtypes in African American women

Background: A review of literature on the expression of Annexin 2 in cancer has shown that there is very limited research work on the association of this protein with breast cancer aggressiveness in African Americans. In the present study, TMA breast tissues from African American women were stained with Annexin 2 antibody to determine the association between the molecular subtypes and Annexin 2 protein expression. Method: An annotated case series of 135 breast cancer tissues archived from 2000 to 2010 was acquired from the Howard University Tumor Registry. The association between ANX2 expression and survival by molecular subtypes Luminal A, Luminal B, HER2, and Triple Negative (TN) was assessed using Multinomial regression, chi-square analysis, and Kaplan-Meir graphs (Stata 11). Results: Our findings show a marked association between ANX2 protein expression in Luminal B and HER2 subtypes unadjusted and when adjusted for age. Borderline differences in tumor grade were found in TN only. Univariately, age (\u3c50, 50 + years) and metastases were highly significant for overall survival, disease-free survival and recurrence-free survival. Stage, tumor size, and nodal involvement were of borderline or greater significance for overall and disease-free survival. ANX2 expression was not significant. Kaplan Meier tests of ANX2 showed significant separation of overall survival by ANX2 protein expression in all breast tumor subtypes. In multivariate analyses comparing TN to Luminal A, ANX2 was not important while controlling for age and grade. Conclusion: ANX2 might be a biomarker of aggressiveness and a relevant candidate biomarker in high risk African American women with Luminal B and HER2 breast cancer

Breast cancer prognosis for young patients

Background/Aims: Breast cancer (BCa) prognostication is a vital element for providing effective treatment for patients with BCa. Studies suggest that ethnicity plays a greater role in the incidence and poor prognosis of BCa in younger women than in their older counterparts. Therefore, the goal of this study was to assess the association between age and ethnicity on the overall final prognosis. Materials and Methods: Nottingham Prognostic Index (NPI) was used to analyze BCa prognosis using Howard University Cancer Center Tumor Registry and the National Cancer Institute\u27s Surveillance, Epidemiology, and End Results BCa datasets. Patients were grouped according to their predicted prognosis based on NPI scheme. Results: There was no correlation between the younger patients compared to their older counterparts for any of the prognostic clusters. The significance of ethnicity in poorer prognosis for younger age is not conclusive either. Conclusion: An extended prognostic tool/system needs to be evaluated for its usefulness in a clinical practice environment

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 patient\u27s 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

Affluence does not influence breast cancer outcomes in African American women

The aim of this study was to determine the impact of race and socioeconomic status on breast tumor clinicopathological features and survival outcomes. This study used breast cancer data from the Washington D.C. Cancer Registry (2000–2010). Logistic regression and survival analysis assessed the association between race, socioeconomic (SES) variables, clinicopathological variables, recurrence-free survival and overall survival. African American (AA) breast cancer patients had an increased risk for stage III, ER-, and PR- breast cancer compared with White and Hispanic breast cancer patients. Additionally, D.C. geographical areas of lower socioeconomic status had higher incidences of stage III and stage IV breast cancer. A nested analysis demonstrated that AAs with higher median incomes compared with AAs with lower incomes revealed no differences for clinicopathological variables, nor were differences found between overall and recurrence-free survival. This study suggests that the biology of breast cancer in AAs could be driving breast cancer disparities

Use of tanning potential as a predictor for prostate cancer risk in African-American men

Background/Aim: Vitamin D deficiency in African-Americans is common due to the high melanin content of the skin that reduces the absorption of UV radiation. To determine if there is a correlation between UV exposure, tanning potential and vitamin D with prostate cancer (PC) risk, we conducted a case-control study of 183 African-American men aged 40 years and older residing in the Washington, DC area. Patients and Methods: PC status was described as a binary variable as the presence or absence of cancer and the environmental factors as continuous variables. We used a logistic regression model describing PC as the response, while age, tanning potential, sunlight and vitamin D were treated as the predictors. Results: Men aged 60 years and older had a seven-fold increased risk for developing PC compared to those aged 50 years and less (p\u3c0.003). Tanning potential was a significant (p=0.05) risk factor for PC, while sunlight exposure and vitamin D were not. Tanning potential was also significant (p=0.044) when adjusted for vitamin D and age. However, tanning potential was only marginally significant when adjusted for sunlight exposure (p=0.064) Conclusion: The findings of this study indicate that tanning potential may be a predictor for PC risk in African-American men

Predictors of Self-Reported Family Health History of Breast Cancer

The objective of this study was to identify predictors of self-reported family health history of breast cancer in an ethnically diverse population of women participating in a breast cancer screening program. Participants completed a self-administered questionnaire about their demography, health, breast health and family health history of breast cancer. The association between family health history of breast cancer and categorical variables were analyzed using the T test, chi square, and multi-nominal logistic regression. Those who were least likely to report a family history of cancer were African Americans (p = 0.02), and immigrant women from South America (p \u3c 0.001) and Africa (p = 0.04). However, 34.4 % reported having a second-degree maternal relative with breast cancer compared to 6.9 % who reported having a second degree paternal relative with breast cancer. Therefore, there is a need to increase efforts to educate families about the importance of collecting and sharing one’s family health history

Vitamin D receptor genetic polymorphisms are associated with PSA level, gleason score and prostate cancer risk in african-american men

Background/Aim: Several studies have revealed an association between single nucleotide polymorphisms (SNPs) in the VDR gene and prostate cancer (PCa) risk in European and Asian populations. To investigate whether VDR SNPs are associated with PCa risk in African-American (AA) men, nine VDR SNPs were analyzed in a case-control study. Materials and Methods: Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. Results: rs731236 and rs7975232 were significantly associated with PCa risk (p\u3c0.05). In the analysis of clinical phenotypes, rs731236, rs1544410 and rs3782905 were strongly associated with high PSA level (p\u3c0.05), whereas rs1544410 and rs2239185 showed a statistically significant association with high Gleason score (p\u3c0.05). Haplotype analysis revealed several VDR haplotypes associated with PCa risk. Additionally, a trend existed, where as the number of risk alleles increased in the haplotype, the greater was the association with risk (ptrend= 0.01). Conclusion: These results suggest that the VDR SNPs may be associated with PCa risk and other clinical pheno types of PCa in AA men