Abstract PD2-01: Personalized serial circulating tumor DNA (ctDNA) analysis in high-risk early stage breast cancer patients to monitor and predict response to neoadjuvant therapy and outcome in the I-SPY 2 TRIAL

Magbanua, Mjm; Brown-Swigart, Lamorna; Hirst, GL; Yau, Christina; Wolf, DM; Ma, Aa; Bergin, Emily; Venters, Sara J.; Sethi, Himanshu; Wu, Hue-Tsi; Salari, Raheleh; Tin, Tony; Sawyer, Sarah; Louie, MC; Zimmermann, B; Lin, C.-H.J.; Liang, WS; Cuyugan, Lori; Enríquez, Daniel; Tripathy, Debu; Forero, Andres; DeMichele, Angela; Liu, M; Delson, AL; Asare, Smita; Esserman, LJ; Veer, Laura van’t

doi:10.1158/1538-7445.sabcs18-pd2-01

Cited by 5 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, ctDNA presence was not significantly associated with pCR or EFS neither at 2 weeks after the treatment start, nor before surgery [75]. Consistent results were reported by a translational sub-study of the I-SPY 2 trial, where high ctDNA at the pre-neoadjuvant time point was associated with tumor burden, aggressive biology and subtype, while the presence of ctDNA at post treatment time point was associated with low pCR [76].…”

Section: Neo-/adjuvant Settingsupporting

confidence: 81%

See 1 more Smart Citation

Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Buono

Gerratana

Bulfoni³

et al. 2019

Cancer Treatment Reviews

100

View full text Add to dashboard Cite

Precision Medicine is becoming the new paradigm in healthcare as it enables better resources allocation, treatment optimization with a potential side-effects reduction and consequent impact on quality of life and survival. This revolution is being catalyzed by liquid biopsy technologies, which provide prognostic and predictive information for advanced cancer patients, without the analytical and procedural drawbacks of tissuebiopsy. In particular, circulating tumor DNA (ctDNA) is gaining momentum as a clinically feasible option capable to capture both spatial and temporal tumor heterogeneity. Several techniques are currently available for ctDNA extraction and analysis, each with its preferential case scenarios and preanalytical implications which must be taken into consideration to effectively support clinical decision-making and to better highlight its clinical utility. Aim of this review is to summarize both analytical developments and clinical evidences to offer a comprehensive update on the deployment of ctDNA in breast cancer's (BC) characterization and treatment.

show abstract

Section: Neo-/adjuvant Settingsupporting

confidence: 81%

“…Magbanua et al [76] Retrospective-prospective analysis of the I-SPY 2 trial ctDNA levels and exploratory biomarkers 100% of ctDNA-positive pts. at T3 (n = 5) did not achieve a pCR Sotiriou et al [75] Retrospective analysis of the NeoALTTO trial…”

Section: Neoadjuvantmentioning

confidence: 99%

Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Buono

Gerratana

Bulfoni³

et al. 2019

Cancer Treatment Reviews

100

View full text Add to dashboard Cite

show abstract

“…At various stages of development, these approaches generally improve on the current limit of detection for ctDNA analysis (~0.1% mutation allele fraction), but each approach has some limitations. Conventional multiplexed PCR-based approaches have been limited by the high background error rates observed (9,22). An alternative is to incorporate UMIs during the first few cycles of PCR to overcome background errors, but this limits molecular conversion because template DNA molecules not incorporated within the first 2-3 cycles are excluded from further analysis (16,25,26).…”

Section: Discussionmentioning

confidence: 99%

Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer

et al. 2019

View full text Add to dashboard Cite

Longitudinal analysis of circulating tumor DNA (ctDNA) has shown promise for monitoring treatment response. However, most current methods lack adequate sensitivity for residual disease detection during or after completion of treatment in patients with nonmetastatic cancer. To address this gap and to improve sensitivity for minute quantities of residual tumor DNA in plasma, we have developed targeted digital sequencing (TARDIS) for multiplexed analysis of patient-specific cancer mutations. In reference samples, by simultaneously analyzing 8 to 16 known mutations, TARDIS achieved 91 and 53% sensitivity at mutant allele fractions (AFs) of 3 in 104 and 3 in 105, respectively, with 96% specificity, using input DNA equivalent to a single tube of blood. We successfully analyzed up to 115 mutations per patient in 80 plasma samples from 33 women with stage I to III breast cancer. Before treatment, TARDIS detected ctDNA in all patients with 0.11% median AF. After completion of neoadjuvant therapy, ctDNA concentrations were lower in patients who achieved pathological complete response (pathCR) compared to patients with residual disease (median AFs, 0.003 and 0.017%, respectively, P = 0.0057, AUC = 0.83). In addition, patients with pathCR showed a larger decrease in ctDNA concentrations during neoadjuvant therapy. These results demonstrate high accuracy for assessment of molecular response and residual disease during neoadjuvant therapy using ctDNA analysis. TARDIS has achieved up to 100-fold improvement beyond the current limit of ctDNA detection using clinically relevant blood volumes, demonstrating that personalized ctDNA tracking could enable individualized clinical management of patients with cancer treated with curative intent.

show abstract

“…The translational sub-study of the ongoing I-SPY 2 trial demonstrated the significance of serial monitoring of ctDNA in predicting response to neo-adjuvant treatment (61). ctDNA analysis of the NeoALTTO trial demonstrated that the detection of PIK3CA and/or TP53 mutations, in the baseline (before neo-adjuvant therapy) plasma sample was correlated with lower rates of pathological complete response, whereas persistent ctDNA detection both at baseline and after 14 days of neo-adjuvant therapy was significantly associated with the lowest rate of pathological complete response (71,72).…”

Section: Resultsmentioning

confidence: 99%

“…ctDNA dynamics could serve as a predictive biomarker independent of the histology. Indeed, the I-SPY 2 trial reported that early ctDNA dynamics could predict response to neo-adjuvant treatment (61), whereas in the basket trial SUMMIT a decrease in ctDNA HER2 mutation variant allele frequency during treatment with the pan-HER inhibitor neratinib was followed by an increase upon radiographically proven progression (59).…”

Section: Discussionmentioning

confidence: 99%

Circulating tumor DNA-based predictive biomarkers in breast cancer clinical trials: a narrative review

Fiste¹,

Liontos²,

Koutsoukos³

et al. 2020

Ann Transl Med

View full text Add to dashboard Cite

Breast carcinoma is the most frequent and the second leading cause of cancer mortality in women worldwide. Current treatment decisions are based on tumor profiling of the initial tissue biopsy.Cancer though evolves both spatially and temporarily in a significant percentage of patients during treatment. However, sequential biopsies from the primary tumor or its metastatic sites are not either convenient or feasible in the majority of cases. In the era of precision medicine, analysis of circulating bloodbased biomarkers in the field of liquid biopsies provides an insight into the dynamic molecular profiling of the primary tumor and its metastases, in a relatively non-invasive way. The latter permits not only patient stratification but also longitudinal evaluation of treatment response, when incorporated into clinical trials. This review summarizes the results from recent and ongoing circulating tumor DNA (ctDNA)based biomarker-driven clinical trials, with respect to ctDNA analysis' predictive role, both in adjuvant, neo-adjuvant, and metastatic setting. Furthermore, current challenges in ctDNA analysis applications are critically discussed, including pre-analytical and analytical issues, and future perspectives in this field, through the conduct of well-designed, multicenter, randomized, large-scale, biomarker-stratified trials, with robust statistical methods. Despite in its infancy, ctDNA analysis holds great promise as a minimally invasive tool regarding tailored, personalized treatment guidance for breast cancer patients.

show abstract

Abstract PD2-01: Personalized serial circulating tumor DNA (ctDNA) analysis in high-risk early stage breast cancer patients to monitor and predict response to neoadjuvant therapy and outcome in the I-SPY 2 TRIAL

Cited by 5 publications

References 0 publications

Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer

Circulating tumor DNA-based predictive biomarkers in breast cancer clinical trials: a narrative review

Contact Info

Product

Resources

About