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At what time points during a patient's treatment for metastatic ER+ breast cancer are you checking liquid NGS for endocrine pathway alterations?

Given that we now have data for PIK3CA (inavolisib, alpelisib), PTEN/AKT/PIK3CA (capivasertib), and ESR1 (elacestrant), when do you look for these alterations? Do you check in specific circumstances or at all phases of progression?
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How frequently do you perform liquid NGS testing for PTEN/AKT/PIK3CA/ESR1 alterations in patients with metastatic ER+ breast cancer?

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4 Answers
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Medical Oncology · Baylor College of Medicine
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Traditionally, liquid NGS testing for PIK3CA, PTEN/AKT/PIK3CA, and ESR1 alterations has been performed at discrete clinical decision points, primarily at progression on endocrine therapy or when considering targeted agents.

Currently, I order NGS at disease onset, even for those who do not fit INAVO ...

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Medical Oncology · Moffitt Cancer Center
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In metastatic ER-positive breast cancer, liquid NGS is most appropriately performed at the time of clinical or radiologic progression, not during stable response, to capture emerging resistance alterations that directly inform therapy selection. Progression often heralds new driver events such as ES...

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Medical Oncology · Mary Lanning Healthcare Morrison Cancer Center/University of Nebraska Medical Center Adjunct Faculty
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Interventional and observational data support checking ctDNA at specific junctures when endocrine resistance commonly emerges. ESR1 mutations are rare prior to endocrine therapy but accumulate under aromatase inhibitor pressure. Testing is most informative at progression on aromatase inhibitor-based...

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Medical Oncology · Warren Alpert Medical School of Brown University
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I typically send peripheral blood for ctDNA analysis for targetable mutations when a patient progresses on 1st-line therapy, in a patient who is treatment-naive, since these patients may respond to first-line therapy with either endocrine therapy alone or the combination of endocrine therapy and a C...

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