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Updated: May 29, 2026
11:47
Time-lapse Imaging of Primary Preneoplastic Mammary Epithelial Cells Derived from Genetically Engineered Mouse Models of Breast Cancer
Published on: February 8, 2013
Distinct epigenetic alterations and accelerated mitotic aging define second primary breast cancers.
Andrés F Bedoya-López1, Javier I J Orozco2,3, Pere Llinàs-Arias1
1Cancer Epigenetics Laboratory, Health Research Institute of the Balearic Islands (IdISBa), Carretera de Valldemossa 79, Palma, Illes Balears, 07120, Spain.
Scientific Reports
|May 27, 2026
Summary
Second primary breast cancers (SPBCs) show distinct epigenetic changes, including suppressed hormone signaling and accelerated aging, linked to poorer outcomes compared to first primary breast cancers (FPBCs). These findings offer insights into SPBC development and potential new therapies.
Area of Science:
- Oncology
- Genomics
- Epigenetics
Background:
- Second primary breast cancers (SPBCs) are increasing, often with worse outcomes than first primary breast cancers (FPBCs).
- The molecular drivers of SPBCs are not well understood.
- Understanding SPBC biology is crucial for improving patient prognosis.
Purpose of the Study:
- To investigate the molecular and epigenetic differences between SPBCs and FPBCs.
- To identify biological drivers contributing to the poorer prognosis of SPBCs.
- To explore potential therapeutic targets for SPBC.
Main Methods:
- Genome-wide DNA methylation profiling of paired SPBC and FPBC samples.
- Integration of multi-omics data (genomic, transcriptomic, proteomic, epigenomic) from The Cancer Genome Atlas.
- Analysis of epigenetic alterations at transcription factor binding sites (TFBSs) and assessment of epigenetic aging using the mitotic clock (epiTOC).
Main Results:
- SPBC tumors exhibited significantly poorer prognosis compared to FPBCs.
- 11,321 differentially methylated CpG sites were identified in SPBCs, with promoter hypermethylation in morphogenesis, hormone signaling, and cell adhesion genes.
- Transcriptomic analysis revealed downregulation of hormone signaling pathways (estrogen, progesterone, androgen) in SPBCs.
- SPBCs showed altered DNA methylation at TFBSs related to aging and cancer, alongside elevated mitotic age, indicating accelerated epigenetic aging.
Conclusions:
- SPBCs are characterized by distinct molecular scars, including suppressed endocrine signaling and accelerated mitotic aging.
- These epigenetic hallmarks may result from cumulative effects of prior malignancy and treatment, contributing to aggressive behavior.
- Findings provide a basis for personalized risk stratification and novel therapeutic strategies for SPBC survivors.
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