HER2 testing and the triple subtypes of breast cancer: A population-based study by race/ethnicity Free

B75

Background
 Since year 2000, standard medical care guidelines have recommended characterizing breast cancer, a non-homogeneous disease that demonstrates marked racial diversity in biology and outcome, by three protein biomarkers (estrogen receptors [ER], progesterone receptors [PR], and human epidermal growth factor receptor2 [HER2]). As of 2007, HER2 data is not collected by U.S. national cancer registries, rendering the population-based understanding of HER2 and associated ‘triple subtypes’ (combined ER/PR/HER2 expression) largely unknown. This study documents the population-based prevalence of HER2 testing, HER2 status, and ER/PR/HER2 subtpes and compares distributions across racial/ethnic and other subgroups.
 Methods
 Medical records and cancer registry abstracts were searched for ER, PR, and HER2 on 1842 females residents of two large metropolitan Atlanta counties diagnosed with breast cancer during 2003-2004 (52.5% White, 44.2% Black, 1.6% Hispanic, and 1.7% ‘Other’). We analyzed HER2 testing status, test results and triple subtypes; overall, and by age, race/ethnicity, other tumor prognostic factors, socio-economic status and vital status. The four triple subtypes were based on whether expression of ER, PR, and HER2 was positive (+) or negative (-): ER-PR-HER2- (Triple negative), ER-PR-HER2+, ER+/PR+HER2-, and ER+/PR+HER2+. Frequency distributions, χ² tests of independence,T-tests, and multivariate logistic regression were employed in analyses.
 Results
 Evidence of HER2 testing was found for over 90% of diagnosed cases; 12.6% positive, 71.7% negative, and 15.7% indeterminable/not assayed. Recommended fluorescent in situ hybridization (FISH) assay for confirmation of the 13.5% scored 2+ by immunohistochemistry (IHC) was documented for nearly 77%, 12.5% of which were positive. HER2 testing and profiles did not differ between Black and White women or by poverty index, but HER2+ tumors were most likely among women under age 50. The most prevalent triple subtype was ER+/PR+HER2- (66.6%), followed by triple negative tumors (TNTs), 19.0%. HER2+ tumors were least prevalent, and fairly equally divided among ER-PR-HER2+ (6.0%) and ER+/PR+HER2+ (8.5%) subtypes. TNTs were most prevalent among Black women (26.8%) and least among White women (12.4%); adjusted Odds Ratio = 2.42, 95% Confidence Interval 1.69-3.49. TNTs also conferred the highest mortality (25.6%). Moreover, TNT mortality significantly differed between Black women (28.2%) and White women (19.8%), (P<0.001). Treatment based on triple subtypes was mostly concordant with recommended guidelines, and did not differ by race/ethnicity.
 Conclusion
 Clinical integration of relatively recent HER2 recommendations is widespread in metropolitan Atlanta and does not differ by race/ethnicity. In accordance with the recommendations, our study indicates that comprehensive capture by cancer registries of this biomarker is feasible and informative. HER2 status does not appear to differ by race, but Black women are more likely to be diagnosed with TNTs. TNTs also bode the worst prognosis, suggesting that the breast cancer subtypes with which women present may contribute to poorer outcome observed among certain racial/ethnic groups. Studies should seek to determine and translate biological mechanisms, with ample size and minority representation, to ultimately improve risk and outcome.