MEME KANSERİNDE TEDAVİYE YANIT NASIL ÖĞRENİLİR
Kan örneği ile aromatase inhibitörlerine yanıt durumu önceden öngörülebilinir.
İngiltere’de yapılan çalışmaya göre hormon resöptörü pozitif menopoza girmiş kadınlarda kullanılan aromatase inhibitörler ESR1 geninin(Bu genin ürettiği reseptör olan ESR1)pozitif olması durumlarında tedaviye yanıt alınamıyor.
Bu çalışma tanı anında hastaların %5.8 bu genin pozitif olduğunu, fakat hastaların %36 tedaviye maruz kaldıktan sonra bu genin pozitifleşmiş olduğu gösterilmiş.
Kan örneği ile doku arasında korelasyon %97 oranında saptanmış. Yani kan testi ile bu analizin doğruluğu çok yüksek.
Sonuç: Menopozda hormon reseptörü pozitif hastalarında kullanılan aromatase inhibitörlerine yanıt kan testiyle öngörülebilir. Genetik analiz için tekrar tekrar doku biyopsisi gerekmez. En önemli ayrıntı, tanı anında düşük oranında bulunan direnç genin tedavi almak ile pozitifleşmesi, yani tedavi altında olanlarda bu analizin tekrarlanma gerekliliğidir. Kan testi bunu uygulanabilir kılmaktadır.
Blood Draw Could Detect AI Resistance in Breast Cancer
News | November 19, 2015 | Breast Cancer
By Anna Azvolinsky, PhD
Image © science photo / Shutterstock.com
Researchers in the United Kingdom have developed a sensitive blood-based assay that can detect mutations in the estrogen receptor gene ESR1, a known mechanism of resistance to aromatase inhibitors (AIs), in the circulating tumor DNA of patients with hormone receptor–positive breast cancer. ESR1 mutations were previously uncovered in analyses of metastatic tumors exposed to aromatase blockers.
The study, published in Science Translational Medicine, demonstrates that these resistance mutations to AIs rarely occur during the initial course of treatment, but rather when hormonal therapy is started in patients with metastatic disease.
Nicholas C. Turner, MD, PhD, a medical oncologist at the Royal Marsden NHS Foundation Trust in the United Kingdom, and colleagues analyzed ESR1 mutations in circulating tumor DNA from blood samples of 171 women with metastatic breast cancer. Mutations in ESR1 were found only among women who had previously been exposed to AI therapy. Only 5.8% of women first exposed to an AI as adjuvant therapy had a detectable ESR1 mutation compared with 36.4% of women who first received an AI for the treatment of metastatic disease (P = .0002). Patients with these mutations had substantially shorter progression-free survival when treated on subsequent AI-based therapy (hazard ratio, 3.1 [95% confidence interval (CI), 1.9–23.1]; P = .0041).
In a separate, independent cohort of 32 breast cancer patients, no ESR1 mutations were detected in the tumor biopsies of patients who progressed on an adjuvant AI, but serial sampling of a metastatic breast cancer patient treated with AI-based therapy detected an ESR1 mutation as the dominant tumor mutation.
The women with detectable ESR1 mutations were three times as likely to progress on an AI.
The results, according to the study authors, suggest that hormonal therapy may not be beneficial in advanced disease, and that early treatment with hormonal therapy is likely to provide the best chance for preventing resistance to an aromatase inhibitor. “The test could give doctors an early warning of treatment failure and, as clinical trials of drugs that target ESR1 mutations are developed, help select the most appropriate treatment for women with advanced cancer,” said Turner in a statement.
The study demonstrated a 97% match in ESR1 mutation status between the blood draw and tumor sample. The blood draw–based test, if confirmed, could be a way to rapidly check breast cancer patients for tumors resistant to AI therapy, and to see if further AI treatment will be beneficial or if the patient needs to switch to a different therapy.
– See more at: http://www.cancernetwork.com/news/blood-draw-could-detect-ai-resistance-breast-cancer?GUID=5A514440-9926-4526-A4A9-DED04057940B&XGUID=&rememberme=1&ts=20112015#sthash.cYdETt6s.dpuf