Priyanka Tiwari
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ER+ (ER/PR+ HER2-) breast tumors are the most common type of breast cancer globally, including in India. Unlike Triple-Negative Breast Cancers (TNBCs), these tumors are treatable with anti-estrogen or aromatase inhibitors. Although endocrine therapy (hormone therapy) is effective, some patients with ER+ breast tumors do not respond to hormone-receptor-specific treatments. This resistance leads to relapse and a lower survival rate.
Genomic Causes of Therapy Resistance
The genomic basis of therapy resistance in ER+ breast tumors is not fully understood. A whole genome sequencing (WGS) study was conducted on tumor and normal tissue samples from ER+ breast cancer patients who exhibited resistance to endocrine therapy and experienced disease relapse.
Indicators of Endocrine Treatment Resistance
A comparative analysis was performed on WGS data from patients who remained disease-free for at least five years post-treatment. The findings revealed:
- A resistance signature involving three key genes: PIK3CA, ESR1, and TP53.
- Disruptions in DNA double-strand break repair and homologous recombination pathways, which significantly correlate with endocrine-therapy resistance and disease relapse.
- Genome instability, including copy-number variations, structural alterations, and high telomere-shortening levels, as indicators of endocrine treatment resistance.
Forecasting Treatment Approaches
Early identification of endocrine therapy resistance based on the genomic landscape of breast tumors can enhance treatment strategies. Research suggests that PARP inhibitors could be repurposed to treat endocrine therapy-resistant breast cancer patients, offering a potential alternative for those who do not respond to traditional hormone therapy.
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