Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response

Zhou, Qing; Gampenrieder, Simon Peter; Frantal, Sophie; Rinnerthaler, Gabriel; Singer, Christian F.; Egle, Daniel; Bartsch, Rupert; Wette, Viktor; Pichler, Angelika; Petru, Edgar; Dubsky, Peter; Bago-Horvath, Zsuzsanna; Fesl, Christian; Rudas, Margaretha; Ståhlberg, Anders; Graf, Ricarda; Weber, Sabrina; Dandachi, Nadia; Filipits, Martin; Gnant, Michael; Balić, Marija; Heitzer, Ellen

doi:10.1158/1078-0432.ccr-21-3231

Cited by 29 publications

(26 citation statements)

References 63 publications

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“…Combining CTC-enumeration with the detection of circulating tumor DNA (ctDNA), shed by tumors during apoptosis, might overcome this problem and considerably increase sensitivity. The prognostic relevance of ctDNA in early breast cancer has been demonstrated in several studies [ 54 , 55 ]. Furthermore, the detection of molecular relapse during breast cancer follow-up via personalized ctDNA profiling has generated a lead-time preceding the clinical detection of metastasis for up to two years.…”

Section: Discussionmentioning

confidence: 99%

Does the Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer Patients Predict the Site of First Metastasis—Results from the Adjuvant SUCCESS A Trial

Trapp

Fasching

Fehm

et al. 2022

Cancers

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The prognostic relevance of circulating tumor cells (CTCs) in breast cancer is well established. However, little is known about the association of CTCs and site of first metastasis. In the SUCCESS A trial, 373 out of 3754 randomized high-risk breast cancer patients developed metastatic disease. CTC status was assessed by the FDA-approved CellSearch®-System (Menarini Silicon Biosystems, Bologna, Italy) in 206 of these patients before chemotherapy and additionally in 159 patients after chemotherapy. CTCs were detected in 70 (34.0%) of 206 patients before (median 2 CTCs, 1–827) and in 44 (27.7%) of 159 patients after chemotherapy (median 1 CTC, 1–124); 16 (10.1%) of 159 patients were CTC-positive at both timepoints. The site of first distant disease was bone-only, visceral-only, and other-site-only in 44 (21.4%), 60 (29.1%), and 74 (35.9%) patients, respectively, while 28 (13.6%) patients had multiple sites of first metastatic disease. Patients with CTCs at both timepoints more often showed bone-only first distant disease (37.5% vs. 21.0%) and first distant disease at multiple sites (31.3% vs. 12.6%) than patients without CTCs before and/or after chemotherapy (p = 0.027). In conclusion, the presence of CTCs before and after chemotherapy is associated with multiple-site or bone-only first-distant disease and may trigger intensified follow-up and perhaps further treatment.

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Section: Discussionmentioning

confidence: 99%

Does the Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer Patients Predict the Site of First Metastasis—Results from the Adjuvant SUCCESS A Trial

Trapp

Fasching

Fehm

et al. 2022

Cancers

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“…In this regard, monitoring tumor dynamics with ctDNA during and after NAT has great potential because it could guide post-NAT management in several ways, including escalation/de-escalation of NAT or adjuvant therapy; delaying or omitting surgery ("watch-and-wait" or non-operative management [NOM]). In fact, positive ctDNA MRD during or after NAT was associated with an increased recurrence risk in locally advanced breast, rectal, gastric/gastroesophageal, and esophageal cancer, as well as in resectable CRC liver metastases, and even outperformed imaging in a few studies [86][87][88][89][90][91][92][93][94][95][96][97][98][99][100]. Recent randomized CheckMate-816 and I-SPY 2 are representative studies demonstrating the potential utility of ctDNA in NAT [90,101].…”

Section: Treatment Monitoring During Neoadjuvant Treatmentmentioning

confidence: 99%

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers

Cha¹,

Kim²,

Han³

2023

Cancer Res Treat

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Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.

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“…After a median follow-up of 4.8 years for survival analysis, this study showed that non-pCR patients positive for ctDNA at T3 have an increased risk of metastatic relapse in comparison with those who were also non-pCR but were ctDNA-negative at T3, who had excellent outcomes [ 137 ]. Zhou et al also evaluated ctDNA in 145 patients and demonstrated that the persistence of ctDNA during the treatment was correlated with non-response to NAC (Residual Cancer Burden of II/III) [ 148 ].…”

Section: Predictive Biomarkers Under Investigationmentioning

confidence: 99%

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine

Derouane

Marcke

Berlière

et al. 2022

Cancers

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Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

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Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response

Abstract: Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally-invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions.

Cited by 29 publications

References 63 publications

Does the Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer Patients Predict the Site of First Metastasis—Results from the Adjuvant SUCCESS A Trial

Does the Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer Patients Predict the Site of First Metastasis—Results from the Adjuvant SUCCESS A Trial

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine

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