Reproducibility and intratumoral heterogeneity of the PAM50 breast cancer assay

Hurson, Amber N.; Hamilton, Alina M.; Olsson, Linnea T.; Kirk, Erin L.; Sherman, Mark E.; Calhoun, Benjamin C.; Geradts, Joseph; Troester, Melissa A.

doi:10.1007/s10549-023-06888-1

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…13 We validated our research version on 272 participants with data on both clinical and research RS R , although we note that the two assays were performed on different sections of the same tumor. RS R assays in different samples of the same tumor were previously reported to have 81% concordance, 41…”

Section: Research-based Rsmentioning

confidence: 94%

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

Van Alsten,

Vohra,

Ivory

et al. 2024

JCO Precis Oncol

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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.

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Section: Research-based Rsmentioning

confidence: 94%

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

Van Alsten,

Vohra,

Ivory

et al. 2024

JCO Precis Oncol

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“…They used Spearman's rank correlation to identify the nearest simple centroid, which was then assigned as one of the following molecular intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like [17,31]. The PAM50 gene microarray panel has been shown to subclassify breast cancer and the risk of relapse (ROR) with a high degree of reproducibility and validity, making it a commonly implemented system [17,32].…”

Section: Evolution Of the Blbc Classification Systemmentioning

confidence: 99%

“…like, and normal-like [17,31]. The PAM50 gene microarray panel has been shown to subclassify breast cancer and the risk of relapse (ROR) with a high degree of reproducibility and validity, making it a commonly implemented system [17,32].…”

Section: Evolution Of the Blbc Classification Systemmentioning

confidence: 99%

MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype

Tariq,

Richard,

Kerin

2023

Biomedicines

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Breast cancer is a heterogeneous disease highlighted by the presence of multiple tumor variants and the basal-like breast cancer (BLBC) is considered to be the most aggressive variant with limited therapeutics and a poor prognosis. Though the absence of detectable protein and hormonal receptors as biomarkers hinders early detection, the integration of genomic and transcriptomic profiling led to the identification of additional variants in BLBC. The high-throughput analysis of tissue-specific micro-ribonucleic acids (microRNAs/miRNAs) that are deemed to have a significant role in the development of breast cancer also displayed distinct expression profiles in each subtype of breast cancer and thus emerged to be a robust approach for the precise characterization of the BLBC subtypes. The classification schematic of breast cancer is still a fluid entity that continues to evolve alongside technological advancement, and the transcriptomic profiling of tissue-specific microRNAs is projected to aid in the substratification and diagnosis of the BLBC tumor subtype. In this review, we summarize the current knowledge on breast tumor classification, aim to collect comprehensive evidence based on the microRNA expression profiles, and explore their potential as prospective biomarkers of BLBC.

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

Van Alsten,

Dunn,

Hamilton

et al. 2024

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: OncotypeDx is a prognostic and predictive genomic assay used in early-stage hormone receptor positive, human epidermal growth factor receptor 2-negative (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 (PDs) and 95% CIs 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 (AHEC) 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%, -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%, -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 HR+/HER2- patients.

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Reproducibility and intratumoral heterogeneity of the PAM50 breast cancer assay

Cited by 3 publications

References 35 publications

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

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

MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype

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

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