Three new first-author papers. One clear message. 🧬

🚨 Three new first-author papers. One clear message: Epigenetics can transform how we detect and prevent breast cancer - non-invasively.

I’m proud to share a new trio of studies, published today in Nature Communications and Communications Medicine. Together, they trace a path from risk prediction to biological insight to prevention through the lens of epigenomic biomarkers, measurable from non-invasive samples like buccal swabs:

🧬🔬 1. Predicting breast cancer risk from buccal swabs (Nature Communications)

We show that DNA methylation in buccal samples reflects breast tissue biology and can predict cancer risk.

⏳🧠 2. Functionally-enriched ageing signatures applied across diverse tissues (Communications Medicine)

This study challenges how we think about epigenetic clocks, showing that discordant ageing between tissues may be linked to cancer susceptibility.

💊🐭 3. Preventing breast cancer with mifepristone, tracked via the epigenome (Communications Medicine)

We demonstrate that mifepristone prevents breast cancer in mice, and that its impact can be monitored in breast and non-invasive samples alike.

🧭 Together, these studies suggest a future where disease risk is detected early and we can guide personalised prevention through epigenomic signatures in non-invasive samples.

Paper 1: buccal epigenome for detection of breast cancer.

Paper 2: discordant aging in breast cancer patients.

Paper 3: prevention of breast cancer through mifeprisone; monitoring via non-invasive epigenome.

References

2025

Systems epigenetic approach towards non-invasive breast cancer detection

Chiara Herzog, Bente Theeuwes, Allison Jones, and 8 more authors

Nature Communications, 2025

Abs

No study has systematically compared the suitability of DNA methylation (DNAme) profiles in non-invasive samples for the detection of breast cancer (BC). We assess non-tumour DNAme in 1,100 cervical, buccal, and blood samples from BC cases and controls and find that cervical samples exhibit the largest nuber of differentially methylated sites, followed by buccal samples. No sites were significant in blood after FDR adjustment. Deriving DNAme-based classifiers for BC detection in each sample type (WID-buccal-, cervical-, or blood-BC), we achieve validation AUCs of 0.75, 0.66, and 0.51, respectively. Buccal and cervical BC-associated DNAme alterations distinguish between BC cases and controls in both surrogate and breast tissue (AUC > 0.88), yet individual sites and the directionality of methylation changes are not identical between these two sample types, and buccal sample DNAme aligns with breast methylation changes more closely. Pending additional validation, these insights may have the potential to improve non-invasive personalized BC prevention.
Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer

Chiara Herzog, Elisa Redl, James Barrett, and 6 more authors

Communications Medicine, 2025

Abs

Aging is a key risk factor for many diseases, including cancer, and a better understanding of its underlying molecular mechanisms may help to prevent, delay, or treat age-related pathologies. Epigenetic alterations such as DNA methylation (DNAme) changes are a hallmark of aging and form the basis of so-called epigenetic clocks, yet their functional relevance and directionality in different organs during disease development is often unclear. Here, we link cell-specific age-related DNAme changes with three key hallmarks of aging and cancer (senescence, promoter methylation in genes associated with stem cell fate, and dysregulated proliferation) to comprehensively dissect their association with current and future cancer development, carcinogen exposure or preventive measures, and mortality using data in different organs from over 12,510 human and 105 mouse samples, benchmarking against existing epigenetic clocks. Our findings offer insights into the association of functionally enriched groups of age-related DNAme changes with cancer, identify sites perturbed earliest during carcinogenesis, as well as those distinct between cancer and reprogramming that could inform strategies to prevent teratoma formation upon in vivo reprogramming. Surprisingly, both mouse and human data reveal accelerated aging in breast cancer tissue but decelerated epigenetic aging in some non-cancer surrogate samples from breast cancer patients, in particular cervical samples. This work provides evidence for discordant systemic tissue aging in breast cancer.
Epigenetic signatures in surrogate tissues are able to assess cancer risk and indicate the efficacy of preventive measures

James E. Barrett*, Chiara Herzog*, Sepideh Aminzadeh-Gohari*, and 14 more authors

Communications Medicine, 2025

Abs

In order to advance personalized primary cancer prevention, surrogate endpoint biomarkers in distant, easy to access tissues (i.e., field defect indicators) reflecting field cancerization in the organ at risk are essential. Here we utilized medroxyprogesterone acetate and 7,12-dimethylbenzanthracene to induce mammary gland cancers in mice. We assessed epigenetic signatures reflective of carcinogen exposure, cell-type composition, mitotic age, and methylation at progesterone receptor binding sites in both, the tissue at risk (normal mammary gland; field cancerization) and distant non-at-risk organs (cervix, oviduct, and blood; field defect indicators), in mice that did and did not develop mammary gland cancers. We demonstrate that the anti-progestine mifepristone reduces the cancer risk by more than 50%. Importantly, the reduction in cancer risk is accompanied by a decline in both field cancerization and field defect indicators; specifically, epigenetic signatures in the cervix are predictive of mammary cancer formation but show tissue-specific directionality. These data encourage further exploration of epigenetic biomarkers in certain field defect-indicating tissues with a view to monitor the efficacy of cancer prevention strategies in humans.

References

2025

Other news