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A systematic review of datasets that can help elucidate relationships among gene expression, race, and immunohistochemistry-defined subtypes in breast cancer.

ABSTRACT: Scholarly requirements have led to a massive increase of transcriptomic data in the public domain, with millions of samples available for secondary research. We identified gene-expression datasets representing 10,214 breast-cancer patients in public databases. We focused on datasets that included patient metadata on race and/or immunohistochemistry (IHC) profiling of the ER, PR, and HER-2 proteins. This review provides a summary of these datasets and describes findings from 32 research articles associated with the datasets. These studies have helped to elucidate relationships between IHC, race, and/or treatment options, as well as relationships between IHC status and the breast-cancer intrinsic subtypes. We have also identified broad themes across the analysis methodologies used in these studies, including breast cancer subtyping, deriving predictive biomarkers, identifying differentially expressed genes, and optimizing data processing. Finally, we discuss limitations of prior work and recommend future directions for reusing these datasets in secondary analyses.

SUBMITTER: Nwosu IO

PROVIDER: S-EPMC8489952 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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A systematic review of datasets that can help elucidate relationships among gene expression, race, and immunohistochemistry-defined subtypes in breast cancer.

Nwosu Ifeanyichukwu O IO Piccolo Stephen R SR

Cancer biology & therapy 20210819 7-9

Scholarly requirements have led to a massive increase of transcriptomic data in the public domain, with millions of samples available for secondary research. We identified gene-expression datasets representing 10,214 breast-cancer patients in public databases. We focused on datasets that included patient metadata on race and/or immunohistochemistry (IHC) profiling of the ER, PR, and HER-2 proteins. This review provides a summary of these datasets and describes findings from 32 research articles ...[more]

PMID: 34412551

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Project description:BackgroundSocioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men.ObjectiveTo compare differences in PC subtype frequency and genomic aggressiveness by self-identified race.Design setting and participantsFive molecular subtype classifiers were applied for 426 Black and 762 White PC patients in the Decipher Genomics Resource Information Database (GRID).Outcome measurements and statistical analysisDifferences in subtype frequency and tumor genomic risk (Decipher score >0.6) by race were evaluated using χ2 tests and multivariable-adjusted logistic regression models.Results and limitationsSubtype frequencies differed by race for four classifiers. Subtypes characterized by the presence of SPOP mutations, SPINK1 overexpression, and neuroendocrine differentiation were more common among Black men. ERG and ETS fusion-positive subtypes were more frequent among White men, with no clear differences for subtypes reflecting luminal versus basal lineage. The hypothesized low-risk Kamoun S2 subtype was associated with a lower Decipher score among White men only (p = 0.01 for heterogeneity), while the aggressive You PCS1 subtype was associated with a higher Decipher score among White men only (p = 0.001 for heterogeneity). The Tomlins ERG+ subtype was associated with a higher Decipher score relative to all other subtypes among Black men, with no association among White men (p = 0.007 for heterogeneity).ConclusionsThe frequency of PC molecular subtypes differed by self-identified race. Additional studies are required to evaluate whether our observations suggest differences in the tumor genomic risk of progression by self-identified race.Patient summaryWe studied five classifiers that identify subtypes of prostate tumors and found that subtypes differed in frequency between Black and White patients. Further research is warranted to evaluate how differences in tumor subtypes may contribute to disparities in prostate cancer mortality.

Project description:BackgroundBreast cancer is the most common female cancer in Africa. Receptor-defined subtypes are a major determinant of treatment options and disease outcomes but there is considerable uncertainty regarding the frequency of poor prognosis estrogen receptor (ER) negative subtypes in Africa. We systematically reviewed publications reporting on the frequency of breast cancer receptor-defined subtypes in indigenous populations in Africa.Methods and findingsMedline, Embase, and Global Health were searched for studies published between 1st January 1980 and 15th April 2014. Reported proportions of ER positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor-2 positive (HER2+) disease were extracted and 95% CI calculated. Random effects meta-analyses were used to pool estimates. Fifty-four studies from North Africa (n=12,284 women with breast cancer) and 26 from sub-Saharan Africa (n=4,737) were eligible. There was marked between-study heterogeneity in the ER+ estimates in both regions (I2>90%), with the majority reporting proportions between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Similarly, large between-study heterogeneity was observed for PR+ and HER2+ estimates (I2>80%, in all instances). Meta-regression analyses showed that the proportion of ER+ disease was 10% (4%-17%) lower for studies based on archived tumor blocks rather than prospectively collected specimens, and 9% (2%-17%) lower for those with ≥ 40% versus those with <40% grade 3 tumors. For prospectively collected samples, the pooled proportions for ER+ and triple negative tumors were 0.59 (0.56-0.62) and 0.21 (0.17-0.25), respectively, regardless of region. Limitations of the study include the lack of standardized procedures across the various studies; the low methodological quality of many studies in terms of the representativeness of their case series and the quality of the procedures for collection, fixation, and receptor testing; and the possibility that women with breast cancer may have contributed to more than one study.ConclusionsThe published data from the more appropriate prospectively measured specimens are consistent with the majority of breast cancers in Africa being ER+. As no single subtype dominates in the continent availability of receptor testing should be a priority, especially for young women with early stage disease where appropriate receptor-specific treatment modalities offer the greatest potential for reducing years of life lost. Please see later in the article for the Editors' Summary.

Dataset Information

A systematic review of datasets that can help elucidate relationships among gene expression, race, and immunohistochemistry-defined subtypes in breast cancer.

Publications

A systematic review of datasets that can help elucidate relationships among gene expression, race, and immunohistochemistry-defined subtypes in breast cancer.

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