Abstract
Simple SummaryBiomarkers found in the blood of patients with hormone receptor positive and HER2 negative metastatic breast cancer are being investigated to understand how patients respond to treatments. Circulating biomarkers have the potential advantage of giving important information with a simple withdrawal of peripheral blood. Here, we review and discuss the recent achievements in the development of circulating biomarkers in patients with metastatic breast cancer treated with CDK4/6 inhibitors and endocrine therapy.CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are the standard treatment for patients with hormone receptor-positive and HER2 negative (HR+/HER2−) metastatic breast cancer. Patients might show intrinsic and acquired resistance, which leads to treatment failure and progression. Circulating biomarkers have the potential advantages of recognizing patients who might not respond to treatment, monitoring treatment effects and identifying markers of acquired resistance during tumor progression with a simple withdrawal of peripheral blood. Genomic alterations on circulating tumor DNA and serum thymidine kinase activity, but also circulating tumor cells, epigenetic or exosome markers are currently being tested as markers of CDK4/6i treatment response, even though none of these have been integrated into clinical practice. In this review, we discuss the recent advancements in the development of circulating biomarkers of CDK4/6i response in patients with HR+/HER2−breast cancer.
Highlights
The majority of breast cancers (BC) expresses hormone receptors (HR), either estrogen (ER) or progesterone (PR) receptors or both and is responsive to endocrine therapies (ET), including aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) like fulvestrant [1]
The potential clinical utility of testing targetable genomic alterations in ctDNA of patients with metastatic breast cancer (MBC) was recently reported [58], but whether PIK3CA, ESR1, RB1 or alterations in other genes at the time of progression to CDK4/6 inhibitors (CDK4/6i) might help personalize subsequent therapeutic strategies remain to be established in future studies
Thymidine kinase 1 (TK1), CDK4, CDK6 and CDK9 expression have been analyzed by droplet-digital PCR (ddPCR) on RNA extracted from exosomes in 40 patients with HR+/HER2− MBC before the administration of palbociclib and ET (T0), and after 3 months of treatment (T1) [73]
Summary
The majority of breast cancers (BC) (around 70%) expresses hormone receptors (HR), either estrogen (ER) or progesterone (PR) receptors or both and is responsive to endocrine therapies (ET), including aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) like fulvestrant [1]. III randomized clinical trials [3,4,5,6,7,8,9,10,11] demonstrated the efficacy of the combination of CDK4/6i and AIs or fulvestrant in prolonging progression free survival (PFS) in the firstwIaInIedostllerris[ta1fetuli2cnoa–lvgsn1sse4de,s]-s.tlwsrIininanhentgihtcsehteihnteteoiapnfrertglfeoyfsnil,scoweatntcrthgyaiinincnoghsfg,laaoapdtfretrdeeodcnigneirntgnretattsiownsnsitoaoleanrybtieemfedarneraiesennfiotastofulyiparnsvaibsiloebvovnoafeeclPfir(ciAaPtlliFLilbnSLst)oAuovirSnaev,driatavjhulmalevlsuafiu(nlrOtrtisvcStEie-)vTnaaa,tnlessdr(hOwposShwee)aclelasodes[n1d2-–l1in4e].
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