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

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 criteria, to both prognosticate and predict treatment response.

For more advanced disease, I also monitor NGS routinely (circa every 6 months) to assess emergent mutations that can be precursors for pr...

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 ESR1 mutations (seen in 30-40% post–AI + CDK4/6i in PADA-1) or PIK3CA mutations, which enable targeted options like elacestrant (EMERALD: HR 0.45 vs SOC) and alpelisib + fulvestrant (SOLAR-1: PFS 11.1 v...

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 regimens and can be repeated at subsequent progressions if previously negative, given the dynamic emergence of subclones. (Betz et al., PMID 37958343; Borkar et al., PMID 40282442; Venetis et al., PM...

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 CDK4/6 inhibitor for many years. On the other hand, in a patient who has recurred on or after completing adjuvant endocrine therapy I will send it immediately, to make sure that there's no evidence of ...