Erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers and fatty acid synthase: a nested case-control study

Abstract

Background: Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS). Methods: We conducted a matched case-control study nested within the Nurses' Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression.

Immunohistochemistry scoring of breast tumor tissue microarrays: A comparison study across three software applications

“…Since 2010, our established workflow in the NHS/NHSII involves digitizing the TMAs using the Pannoramic Scan and analyzing the images using Definiens Tissue Studio® (version 4.4.2; Definiens AG, Munich, Germany; Heng lab). 8 , 13 , 19 In 2021, the Spatial Transcriptomics Unit at BIDMC acquired the PhenoImager HT scanner and its companion image analysis software, inForm® (version 2.5). The older Pannoramic Scan’s .mrxs file format was incompatible with inForm while the newer PhenoImager HT .qptiff files were incompatible with Definiens version 4.4.2.…”

“… [1] , [2] , [3] , [4] For example, within the Nurses’ Health Studies (NHS), we, the authors, constructed TMAs of normal breast lobules to identify biomarkers associated with subsequent breast cancer development. [5] , [6] , [7] , [8] We also utilized TMAs of breast tumors to study associations between: (1) breast cancer risk factors and tumor molecular subtypes, [9] , [10] , [11] , [12] , [13] and (2) tumor biomarkers and breast cancer prognosis. [14] , [15] , [16] , [17] …”

“…Since 2010, our approach in the NHS has been to: (1) use the Definiens Tissue Studio® software to semi-automate the quantification of a marker’s IHC expression on digitized TMAs; (2) randomly select 1 TMA for manual scoring by a pathologist; and (3) benchmark the software-derived scores against manual scores for that TMA to assess the reliability of the IHC quantification by Definiens. 8 , 13 , 19 …”

Contribution of n-3 Long-Chain Polyunsaturated Fatty Acids to the Prevention of Breast Cancer Risk Factors

“…Only 16 of the 680 studies are consistent with breast cancer, of which, 12 are less than 6 years old (at the completion date of the study), and only 2 trials have been completed and have results, whereas the other 10 trials are active or in the recruitment phase (Table 1). Finally, fatty acid profiles in erythrocyte membranes appear as a relevant biomarker of breast cancer risk [108,109]. For example, this method was used to show that n-3 index was significantly lower in breast cancer patients than in healthy patients [110].…”

Circulating plasma phospholipid fatty acid levels and breast cancer risk in the Cancer Prevention Study‐II Nutrition Cohort

“…In EPIC, higher levels of industrial trans fatty acids (iTFAs) were also associated with higher risk of ER−, but not ER positive (+) breast cancer 11 . The NHS II study also reported a positive association for iTFAs and breast cancer risk but only for women with BMIs ≥25 kg/m 2 12 and in a smaller sample (235 cases, 235 controls) TFAs were associated with high fatty acid synthase (FAS) in breast cancer tumor tissue 13 …”