Analysis of ctDNA offers a minimal-invasive approach for monitoring treatment response in pts with breast cancer (BC). Serial ctDNA testing during neoadjuvant therapy (NAT) may provide early indicators of resistance and disease progression.
Plasma samples (n=178) collected from 34 pts with eBC (stage II-III) were prospectively analyzed using a personalized, tumor-informed ctDNA assay (SignateraTM bespoke mPCR-NGS). All pts received standard of care NAT (anthracycline, taxane). Longitudinal blood samples were collected at the time of diagnosis (baseline), followed by on treatment (every 3 weeks) with a median of 6 samples (1-10). ctDNA status and dynamics were correlated with clinicopathological features.
At baseline, ctDNA was detected in 85% (29/34) of pts. ctDNA-positivity was observed in 95% (18/19)of pts with triple-negative breast cancer and in 73% (11/15) pts with HER2+ disease at baseline. ctDNA was detectable in 78% (18/23) of pts with T1-2 disease and 100% (11/11) of pts with T3-4 disease. At baseline, 75% (15/20) of low-/intermediate-grade disease had detectable ctDNA; all cases with high-grade disease were ctDNA positive (14/14), irrespective of nodal status. Of the 19 with surgical outcomes, 9 pts with longitudinal samples achieved pathologic complete response (pCR). While all 9 pts were ctDNA positive at baseline, 67% (6/9) became ctDNA negative after the first cycle of treatment. Among those with residual disease (pT1c-T3), 50% (2/4) remained ctDNA positive after the first cycle of therapy. Interestingly, one pt with inflammatory BC failed to clear ctDNA despite achieving pCR and remained ctDNA positive after definitive surgery. Based on unfavorable ctDNA dynamics and high-risk disease the pt was initiated on ado-trastuzumab adjuvant therapy. Association between ctDNA dynamics and pt clinical outcome will be presented.
This study demonstrates the feasibility of ctDNA detection in pts with eBC treated with NAT. ctDNA monitoring during NAT can facilitate real-time assessment of treatment response and resistance and predict pCR.
NCT05333874.
The authors.
Natera supported us with patient testing for ctDNA. Funding was institutional funding-through Rutgers Cancer Institute if New Jersey.
M. George: Financial Interests, Institutional, Funding: Incyte, Oncolytics; Financial Interests, Personal, Advisory Board: Seattle Genetics, OBI Pharma. E. Kalashnikova: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. R. Watters: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. A.A. Rodriguez: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. S. Ganesan: Financial Interests, Personal, Advisory Board: Merck, Roche, Foundation Medicine, Ipsen, Foghorn Therapeutics, SilaGene, EQRx, Kayothera; Financial Interests, Institutional, Funding: M2GEN, Gandeeva; Other, Spouse employed: Merck. D. Toppmeyer: Financial Interests, Personal, Other, Spouse employed: Merck. M.C. Liu: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera; Financial Interests, Institutional, Research Grant: Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Financial Interests, Institutional, Advisory Board: AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax; Financial Interests, Institutional, Other, Travel reimbursement: AstraZeneca, Genomic Health, Ionis. All other authors have declared no conflicts of interest.