Dataset Information

FOXA1 Protein Expression in ER⁺ and ER^- Breast Cancer in Relation to Parity and Breastfeeding in Black and White Women.

ABSTRACT:

Background

Forkhead box protein A1 (FOXA1) promotes luminal differentiation, and hypermethylation of the gene can be a mechanism of developing estrogen receptor-negative (ER^-) breast cancer. We examined FOXA1 in breast tumor and adjacent normal tissue in relation to reproductive factors, particularly higher parity and no breastfeeding, that are associated with ER^- tumors.

Methods

We performed IHC for FOXA1 in breast tumors (n = 1,329) and adjacent normal tissues (n = 298) in the Women's Circle of Health Study (949 Blacks and 380 Whites). Protein expression levels were summarized by histology (H) scores. Generalized linear models were used to assess FOXA1 protein expression in relation to reproductive factors by ER status.

Results

ER-positive (ER⁺) versus ER^- tumors had higher FOXA1 protein expression (P < 0.001). FOXA1 expression was higher in tumor versus paired adjacent normal tissue in women with ER⁺ or non-triple-negative cancer (both P < 0.001), but not in those with ER^- or triple-negative cancer. Higher number of births (1, 2, and 3+) was associated with lower FOXA1 protein expression in ER⁺ tumors [differences in H score, or β = -8.5; 95% confidence interval (CI), -15.1 to -2.0], particularly among parous women who never breastfed (β = -10.4; 95% CI, -19.7 to -1.0), but not among those who breastfed (β = -7.5; 95% CI, -16.9 to 1.8). The associations for ER^- tumors were similar, although they were not statistically significant.

Conclusions

In this tumor-based study, higher parity was associated with lower FOXA1 expression in ER⁺ tumors, and breastfeeding may ameliorate the influence.

Impact

These findings contribute to our understanding of FOXA1 methylation and breast cancer etiology.

SUBMITTER: Cheng TD

PROVIDER: S-EPMC7007352 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The NanoString GeoMx digital spatial profiling is a new multiplexed platform that quantifies the abundance of tumor- and immune-related proteins in a spatially resolved manner. We performed DSP for the simultaneous assessment of 52 analytes within spatially resolved tissue compartments defined by pan-cytokeratin expression. We compared protein targets between 94 African American/Black and 65 European American/White cases, tumor and stromal tissue compartments, estrogen receptor alpha (ER)-positive and ER-negative cases, and explored potential biomarkers of survival. Of 33 analytes with robust signal for analysis, results were highly replicable. For a subset of markers, correlative analyses between DSP analytes and traditional immunohistochemistry scores revealed moderate to very strong associations between the two platforms. Similarly, DSP analytes and gene expression scores were concordant for 21 of 25 markers with overlap between the two datasets. Several analytes varied by ER status, and across the 25 immune markers surveyed, 14 had a significant inverse association with ER expression. B7 homolog 3 (B7-H3; encoded by CD276) was the only analyte to show a significant difference by race, being lower in both the tumor and stromal compartments in Black women. DSP markers that were associated with survival included CD8, CD25, CD56, CD127, EpCAM, ER, Ki-67, and STING. We conclude that DSP is an efficient tool for screening tumor- and immune-related markers in a simultaneous fashion and yields results that are concordant with established immune profiling assays. DSP immune analytes were inversely associated with ER expression, in agreement with a substantial body of previous work that documents higher immune infiltration in ER-negative breast cancers. This technology revealed that scores of the B7-H3 protein were significantly lower in breast cancers from Black women compared with White women, an intriguing finding that requires replication in independent and racially diverse female populations.

Dataset Information

FOXA1 Protein Expression in ER⁺ and ER^- Breast Cancer in Relation to Parity and Breastfeeding in Black and White Women.

Background

Methods

Results

Conclusions

Impact

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

FOXA1 Protein Expression in ER+ and ER- Breast Cancer in Relation to Parity and Breastfeeding in Black and White Women.

Background

Methods

Results

Conclusions

Impact

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

FOXA1 Protein Expression in ER⁺ and ER^- Breast Cancer in Relation to Parity and Breastfeeding in Black and White Women.