Dataset Information

Borderline Estrogen Receptor-Positive Breast Cancers in Black and White Women.

ABSTRACT: BACKGROUND:Some breast tumors expressing greater than 1% and less than 10% estrogen receptor (ER) positivity (ER-borderline) are clinically aggressive; others exhibit luminal biology. Prior ER-borderline studies included few black participants. METHODS:Using the Carolina Breast Cancer Study (phase I: 1993-1996; 2: 1996-2001; 3: 2008-2013), a population-based study that oversampled black women, we compared ER-borderline (n?=?217) to ER-positive (n?=?1885) and ER-negative (n?=?757) tumors. PAM50 subtype and risk of recurrence score (ROR-PT, incorporates subtype, proliferation, tumor size) were measured. Relative frequency differences (RFD) were estimated using multivariable linear regression. Disease-free interval (DFI) was evaluated by ER category and endocrine therapy receipt, overall and by race, using Kaplan Meier and Cox models. Statistical tests were two-sided. RESULTS:ER-borderlines were more frequently basal-like (RFD = +37.7%, 95% confidence interval [CI]?=?27.1% to 48.4%) and high ROR-PT (RFD = +52.4%, 95% CI?=?36.8% to 68.0%) relative to ER-positives. Having a high ROR-PT ER-borderline tumor was statistically significantly associated with black race (RFD = +26.2%, 95% CI?=?9.0% to 43.3%). Compared to ER-positives, DFI of ER-borderlines treated with endocrine therapy was poorer but not statistically significantly different (hazard ratio [HR] = 2.03, 95% CI?=?0.89% to 4.65%), whereas DFI was statistically significantly worse for ER-borderlines without endocrine therapy (HR?=?3.33, 95% CI?=?1.84% to 6.02%). However, black women with ER-borderline had worse DFI compared to ER-positives, even when treated with endocrine therapy (HR?=?2.77, 95% CI?=?1.09% to 7.04%). CONCLUSIONS:ER-borderline tumors were genomically heterogeneous, with survival outcomes that differed by endocrine therapy receipt and race. Black race predicted high-risk ER-borderlines and may be associated with poorer endocrine therapy response.

SUBMITTER: Benefield HC

PROVIDER: S-EPMC7357313 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Borderline Estrogen Receptor-Positive Breast Cancers in Black and White Women.

Benefield Halei C HC Allott Emma H EH Reeder-Hayes Katherine E KE Perou Charles M CM Carey Lisa A LA Geradts Joseph J Sun Xuezheng X Calhoun Benjamin C BC Troester Melissa A MA

Journal of the National Cancer Institute 20200701 7

<h4>Background</h4>Some breast tumors expressing greater than 1% and less than 10% estrogen receptor (ER) positivity (ER-borderline) are clinically aggressive; others exhibit luminal biology. Prior ER-borderline studies included few black participants.<h4>Methods</h4>Using the Carolina Breast Cancer Study (phase I: 1993-1996; 2: 1996-2001; 3: 2008-2013), a population-based study that oversampled black women, we compared ER-borderline (n = 217) to ER-positive (n = 1885) and ER-negative (n = 757) ...[more]

PMID: 31742342

Similar Datasets

Project description:BackgroundDirectly comparing gene expression profiles of estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancers cannot determine whether differentially expressed genes between these two subtypes result from dysregulated expression in ER+ cancer or ER- cancer versus normal controls, and thus would miss critical information for elucidating the transcriptomic difference between the two subtypes.Principal findingsUsing microarray datasets from TCGA, we classified the genes dysregulated in both ER+ and ER- cancers versus normal controls into two classes: (i) genes dysregulated in the same direction but to a different extent, and (ii) genes dysregulated to opposite directions, and then validated the two classes in RNA-sequencing datasets of independent cohorts. We showed that the genes dysregulated to a larger extent in ER+ cancers than in ER- cancers enriched in glycerophospholipid and polysaccharide metabolic processes, while the genes dysregulated to a larger extent in ER- cancers than in ER+ cancers enriched in cell proliferation. Phosphorylase kinase and enzymes of glycosylphosphatidylinositol (GPI) anchor biosynthesis were upregulated to a larger extent in ER+ cancers than in ER- cancers, whereas glycogen synthase and phospholipase A2 were downregulated to a larger extent in ER+ cancers than in ER- cancers. We also found that the genes oppositely dysregulated in the two subtypes significantly enriched with known cancer genes and tended to closely collaborate with the cancer genes. Furthermore, we showed the possibility that these oppositely dysregulated genes could contribute to carcinogenesis of ER+ and ER- cancers through rewiring different subpathways.ConclusionsGPI-anchor biosynthesis and glycogenolysis were elevated and hydrolysis of phospholipids was depleted to a larger extent in ER+ cancers than in ER- cancers. Our findings indicate that the genes oppositely dysregulated in the two subtypes are potential cancer genes which could contribute to carcinogenesis of both ER+ and ER- cancers through rewiring different subpathways.

Dataset Information

Borderline Estrogen Receptor-Positive Breast Cancers in Black and White Women.

Publications

Borderline Estrogen Receptor-Positive Breast Cancers in Black and White Women.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets