Extremely-sensitive ctDNA testing detected baseline ctDNA in HR-positive early breast most cancers, linking it to bigger tumors, increased residual most cancers burden and elevated recurrence charges after neoadjuvant endocrine remedy.
Sufferers with hormone receptor (HR)-positive early breast most cancers who underwent ultra-sensitive tissue-free circulating tumor DNA (ctDNA) demonstrated detections of ctDNA, in accordance with findings from a section 2 trial offered on the 2024 San Antonio Breast Most cancers Symposium.
The presence of ctDNA at baseline within the affected person inhabitants was linked with a bigger pathological tumor measurement and better residual most cancers burden (RCB) scores after neoadjuvant endocrine remedy. Current ctDNA after neoadjuvant endocrine remedy was related to increased charges of recurrence, Dr. Albert Grinshpun and colleagues famous within the presentation.
The section 2 PELOPS trial included 49 sufferers with levels 1 to three HR-positive, HER2-negative breast most cancers and have been randomly assigned to obtain both neoadjuvant endocrine remedy plus Ibrance (palbociclib; 35 sufferers) or neoadjuvant endocrine remedy alone (13 sufferers).
“This research is the primary investigation into the dynamics of ctDNA throughout neoadjuvant endocrine remedy utilizing the Guardant Infinity platform,” Albert Grinshpun and colleagues wrote of their poster. “Our findings recommend that ctDNA has the potential to offer worthwhile insights into tumor burden, sensitivity to endocrine remedy and the emergence of endocrine resistance mutations.”
Glossary:
Circulating tumor DNA (ctDNA): traces of most cancers cells remaining within the bloodstream.
Neoadjuvant: therapy given earlier than surgical procedure.
Residual most cancers burden (RCB) rating: a system that estimates how a lot most cancers shall be left within the physique after neoadjuvant therapy. A rating of zero means there’s no residual most cancers, whereas a rating of three means there’s an intensive quantity of residual most cancers.
Endocrine remedy: hormone remedy that both provides, blocks or removes hormones to deal with most cancers.
Recurrence: return of most cancers after therapy.
Lobular breast most cancers: most cancers that begins within the milk-producing glands.
Tumor fraction ranges: the measurement of ctDNA ranges in a (blood) pattern.
Distant recurrence: most cancers that has returned after therapy however in a distinct area of the physique from the place it originated.
Grinshpun is the Goldfarb Superior Breast Most cancers fellow on the Breast Oncology Heart at Dana-Farber Most cancers Institute in Boston.
ctDNA Detection in HR-Optimistic Early Breast Most cancers
The research’s predominant aim was to judge whether or not baseline ctDNA and dynamic modifications throughout neoadjuvant endocrine remedy as a biomarker might assist information systemic therapy selections, Grinshpun and colleagues famous on the poster.
At baseline, ctDNA positivity (current ctDNA) was proven in 19% of sufferers and ctDNA negativity (no presence of ctDNA) was proven in 30% of sufferers. Earlier than sufferers underwent surgical procedure and after therapy, ctDNA positivity was proven in 6% of sufferers and ctDNA negativity was proven in 38% of sufferers.
Twenty-six of 40 sufferers (65%) with undetectable ctDNA at baseline remained with undetectable ctDNA after receiving neoadjuvant endocrine remedy. Particularly, six sufferers (14.6%) with lobular breast most cancers and a RCB rating of three had current ctDNA at baseline and earlier than surgical procedure, in accordance with the poster. Amongst these six sufferers, 4 (67%) developed metastatic breast most cancers recurrence inside three years of surgical procedure. Tumor fraction ranges have been reported to be decrease earlier than surgical procedure in contrast with baseline in these respective sufferers.
Amongst 40 sufferers within the research, ctDNA dynamics have been categorized by persistent or emergent ctDNA, cleared ctDNA or no ctDNA in any respect. At baseline and earlier than surgical procedure, ctDNA was persistent or emergent in six sufferers (15%) and in 4 sufferers (66.7%) at three-year distant recurrence. Of observe, no sufferers within the research turned ctDNA optimistic earlier than surgical procedure and 20% of sufferers skilled ctDNA clearance (no current ctDNA) from baseline to earlier than surgical procedure. At baseline and earlier than surgical procedure, no ctDNA was reported in 26 sufferers (65%) and in a single affected person (3.8%) at three-year distant recurrence.
“These outcomes are restricted by the pattern measurement however benefit additional investigation of the function of ctDNA as a software to foretell sensitivity to endocrine remedy and long-term outcomes,” Grinshpun and colleagues concluded. “Such a software may very well be worthwhile in tailoring surgical and systemic therapy approaches, notably given the continuing growth of novel endocrine therapies and the addition of CDK4/6 inhibitors within the adjuvant setting.”
Reference:
“PS9-08: Extremely-sensitive detection of circulating tumor DNA (ctDNA) in sufferers present process neoadjuvant endocrine remedy for hormone receptor-positive (HR+) early breast most cancers” by Dr. Albert Grinshpun, et al. Introduced at: 2024 San Antonio Breast Most cancers Symposium; December 10-13, 2024; San Antonio, TX. Summary PS9-08.
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