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Aspirin interacts with epigenetics to influence breast cancer mortality

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Intersection of breast cancer, epigenetics, and aspirin

This study offers new insights into the intersection of epigenetics, prediagnosis aspirin use, and breast cancer survival at a time when there is an urgent need to understand why some women respond differently to treatment and to find cost-effective therapies for the disease.

Epigenetics is a promising avenue of investigation because epigenetic shifts, such as DNA methylation, that impact the genes responsible for cell behavior and DNA damage and repair are known to contribute to and exacerbate cancer. These epigenetic signatures could act as biomarkers for risk in cancer and also aid with more effective treatment approaches. For example, aspirin is known to affect DNA methylation at certain sites in colon cancer, hence this study’s hypothesis that pre–cancer diagnosis aspirin use would interact with epigenetic signatures and influence breast cancer outcomes.

Kristen M. C. Malecki, PhD, is from the department of population health sciences in the School of Medicine and Public Health at the University of Wisconsin, Madison. The comments are adapted from an accompanying editorial (Cancer. 2019 Aug 12. doi: 10.1002/cncr.32365). Dr. Malecki declared support from the National Institutes of Health, National Institute for Environmental Health Sciences Breast Cancer, and the Environment Research Program.


 

FROM CANCER

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

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