Differences in 21-Gene and PAM50 Recurrence Scores in Younger and Black Women With Breast Cancer.

PURPOSE: Genomic tests, such as the Oncotype Dx 21-gene and Prosigna risk of recurrence (ROR-P) assay, are commonly used for breast cancer prognostication. Emerging data suggest variability between assays, but this has not been compared in diverse populations. MATERIALS AND METHODS: RNA sequencing was performed on 647 previously untreated stage I-III estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors in the Carolina Breast Cancer Study, which oversampled Black and younger women (age <50 years at diagnosis), using research versions of two common RNA-based prognostic assays: ROR-PR and the 21-gene recurrence score (RSR). Relative frequency differences and 95% CIs were estimated for associations with race and age, and hazards of 5-year local or distant recurrence were modeled with Cox regression. Proliferation and estrogen module scores from each assay, representing broad activity of genes in those pathways, were examined to guide interpretation of differences between tests. RESULTS: Among both younger and older individuals, Black women had higher frequency of intermediate and high ROR-PR scores than non-Black women. Race was not significantly associated with RSR in either age group. High (hazard ratio [HR], 4.67 [95% CI, 1.73 to 12.70]) and intermediate (HR, 2.12 [95% CI, 0.98 to 4.62]) ROR-PR scores were associated with greater risk of recurrence, but RSR did not predict recurrence. RSR emphasized estrogen over proliferation modules, whereas ROR-PR emphasized proliferation. Higher proliferation scores were associated with younger age and Black race in both assays. Modifications to the RSR algorithm that increased emphasis on proliferation improved prognostication in this diverse population. CONCLUSION: ROR-PR and the 21-gene RSR differentially emphasize estrogen-related and proliferative biology. The emphasis of 21-gene RS on estrogen-related biology and lower endocrine therapy initiation among Black women may contribute to poorer prognostic ability in heterogeneously treated populations.

BIRC5 expression by race, age and clinical factors in breast cancer patients.

PURPOSE: Survivin/BIRC5 is a proliferation marker that is associated with poor prognosis in breast cancer and an attractive therapeutic target. However, BIRC5 has not been well studied among racially diverse populations where aggressive breast cancers are prevalent. EXPERIMENTAL DESIGN: We studied BIRC5 expression in association with clinical and demographic variables and as a predictor of recurrence in 2174 participants in the Carolina Breast Cancer Study (CBCS), a population-based study that oversampled Black (n = 1113) and younger (< 50 years; n = 1137) participants with breast cancer. For comparison, similar analyses were conducted in The Cancer Genome Atlas [TCGA N = 1094, Black (n = 183), younger (n = 295)]. BIRC5 was evaluated as a continuous and categorical variable (highest quartile vs. lower three quartiles). RESULTS: Univariate, continuous BIRC5 expression was higher in breast tumors from Black women relative to non-Black women in both estrogen receptor (ER)-positive and ER-negative tumors and in analyses stratified by stage (i.e., within Stage I, Stage II, and Stage III/IV tumors). Within CBCS and TCGA, BIRC5-high was associated with young age (< 50 years) and Black race, as well as hormone receptor-negative tumors, non-Luminal A PAM50 subtypes, advanced stage, and larger tumors (> 2 cm). Relative to BIRC5-low, BIRC5-high tumors were associated with poor 5-year recurrence-free survival (RFS) among ER-positive tumors, both in unadjusted models [HR (95% CI): 2.7 (1.6, 4.6)] and after adjustment for age and stage [Adjusted HR (95% CI): 1.87 (1.07, 3.25)]. However, this relationship was not observed among ER-negative tumors [Crude HR (95% CI): 0.7 (0.39, 1.2); Adjusted HR (95% CI): 0.67 (0.37, 1.2)]. CONCLUSION: Black and younger women with breast cancer have a higher burden of BIRC5-high tumors than older and non-Black women. Emerging anti-survivin treatment strategies may be an important future direction for equitable breast cancer outcomes.

Disparities in OncotypeDx Testing and Subsequent Chemotherapy Receipt by Geography and Socioeconomic Status.

BACKGROUND: OncotypeDx is a prognostic and predictive genomic assay used in early-stage hormone receptor-positive, HER2- (HR+/HER2-) breast cancer. It is used to inform adjuvant chemotherapy decisions, but not all eligible women receive testing. We aimed to assess variation in testing by demographics and geography, and to determine whether testing was associated with chemotherapy. METHODS: For 1,615 women in the Carolina Breast Cancer Study with HR+/HER2-, Stage I-II tumors, we estimated prevalence differences (PD) and 95% confidence intervals (CI) for receipt of OncotypeDx genomic testing in association with and sociodemographic characteristics. We assessed associations between testing and chemotherapy receipt overall and by race. Finally, we calculated the proportion of eligible women receiving OncotypeDx by county-level rurality, census tract-level socioeconomic status, and Area Health Education Center regions. RESULTS: 38% (N = 609) of potentially eligible women were tested, with lower testing prevalences in Black (31%; PD, -11%; 95% CI, -16%-6%) and low-income women (24%; PD, -20%; 95% CI, -29% to -11%) relative to non-Black and higher income women. Urban participants were less likely to be tested than rural participants, though this association varied by region. Among women with low genomic risk tumors, tested participants were 29% less likely to receive chemotherapy than untested participants (95% CI, -40% to -17%). Racial differences in chemotherapy were restricted to untested women. CONCLUSIONS: Both individual and area-level socioeconomics predict likelihood of OncotypeDx testing. IMPACT: Variable adoption of OncotypeDx by socioeconomics and across geographic settings may contribute to excess chemotherapy among patients with HR+/HER2- cancers. See related In the Spotlight, p. 635.