Outcome disparities in African American women with triple negative breast cancer: a comparison of epidemiological and molecular factors between African American and Caucasian women with triple negative breast cancer.

BACKGROUND: Although diagnosed less often, breast cancer in African American women (AAW) displays different characteristics compared to breast cancer in Caucasian women (CW), including earlier onset, less favorable clinical outcome, and an aggressive tumor phenotype. These disparities may be attributed to differences in socioeconomic factors such as access to health care, lifestyle, including increased frequency of obesity in AAW, and tumor biology, especially the higher frequency of triple negative breast cancer (TNBC) in young AAW. Improved understanding of the etiology and molecular characteristics of TNBC in AAW is critical to determining whether and how TNBC contributes to survival disparities in AAW. METHODS: Demographic, pathological and survival data from AAW (n = 62) and CW (n = 98) with TNBC were analyzed using chi-square analysis, Student's t-tests, and log-rank tests. Frozen tumor specimens were available from 57 of the TNBC patients (n = 23 AAW; n = 34 CW); RNA was isolated after laser microdissection of tumor cells and was hybridized to HG U133A 2.0 microarrays. Data were analyzed using ANOVA with FDR <0.05, >2-fold difference defining significance. RESULTS: The frequency of TNBC compared to all BC was significantly higher in AAW (28%) compared to CW (12%), however, significant survival and pathological differences were not detected between populations. Gene expression analysis revealed the tumors were more similar than different at the molecular level, with only CRYBB2P1, a pseudogene, differentially expressed between populations. Among demographic characteristics, AAW consumed significantly lower amounts of caffeine and alcohol, were less likely to breastfeed and more likely to be obese. CONCLUSIONS: These data suggest that TNBC in AAW is not a unique disease compared to TNBC in CW. Rather, higher frequency of TNBC in AAW may, in part, be attributable to the effects of lifestyle choices. Because these risk factors are modifiable, they provide new opportunities for the development of risk reduction strategies that may decrease mortality by preventing the development of TNBC in AAW.

Tissue imprints: assessing their potential for routine biobanking collection.

Biomedical research depends on the availability of good quality biospecimens. Unfortunately, certain specimens are scarce due to disease rarity or size restrictions of surgical materials. To increase access to limited surgical specimens, Biobanks need to reassess and adjust their collection programs. We evaluated the feasibility of adapting "touch imprints" to gain access to limited surgical specimens as well as to maximize the use of "precious" specimens. We utilized 12 kidney samples for touch imprints on defined areas of microscope glass slides and FTA paper. DNA was isolated from glass slides on the day of preparation, Day 0, and from glass slide and FTA paper preparations after two weeks of storage at room temperature and -80°C. Yield and purity of DNA from reference kidney samples were compared to DNA from the touch imprints and the quality determined by real-time PCR using the amplification of Cyclophilin A (Cyc A) as an index. DNA quality for glass slides at Day 0 was not significantly different from DNA after two weeks at room temperature (glass at room temperature; p=0.111 and 0.097, yield and purity, respectively) and after two weeks at -80°C (glass -80°C; p=0.358 and 0.281, yield and purity, respectively). Glass slide DNA at room temperature and -80°C were not significantly different (p=0.795 and 0.146 for yield and purity, respectively). DNA from FTA paper at room temperature and from FTA paper at -80°C were significantly different from glass at room temperature and glass at -80°C (p=0.002, respectively). Threshold values for Cyc A were ≤28 for the reference DNA and ≤32 for DNA from glass and FTA paper. This study demonstrates that touch preparations on microscope glass slides and FTA paper can provide sufficient and good quality DNA suitable for PCR. Touch imprints could therefore be adopted by biobanks to collect and bank biological materials from limited surgical specimens.

Molecular alterations associated with breast cancer mortality.

BACKGROUND: Breast cancer is a heterogeneous disease and patients with similar pathologies and treatments may have different clinical outcomes. Identification of molecular alterations associated with disease outcome may improve risk assessment and treatments for aggressive breast cancer. METHODS: Allelic imbalance (AI) data was generated for 122 invasive breast tumors with known clinical outcome. Levels and patterns of AI were compared between patients who died of disease (DOD) and those with ≥5 years disease-free survival (DFS) using Student t-test and chi-square analysis with a significance value of P<0.05. RESULTS: Levels of AI were significantly higher in tumors from the 31 DOD patients (28.6%) compared to the 91 DFS patients (20.1%). AI at chromosomes 7q31, 8p22, 13q14, 17p13.3, 17p13.1 and 22q12.3 was associated with DOD while AI at 16q22-q24 was associated with DFS. After multivariate analysis, AI at chromosome 8p22 remained an independent predictor of breast cancer mortality. The frequency of AI at chromosome 13q14 was significantly higher in patients who died ≥5 years compared to those who died <5 years from diagnosis. CONCLUSION: Tumors from DOD compared to DFS patients are marked by increased genomic instability and AI at chromosome 8p22 is significantly associated with breast cancer morality, independent of other clinicopathological factors. AI at chromosome 13q14 was associated with late (>5-years post-diagnosis) mortality but not with death from disease within five years, suggesting that patients with short- and long-term mortality may have distinct genetic diseases.