Association of Circulating Tumor DNA With Disease-Free Survival in Breast Cancer

Cullinane, Carolyn; Fleming, Christina; O’Leary, Donal Peter; Hassan, Fara; Kelly, Louise; O’Sullivan, M. J.; Corrigan, Mark; Redmond, H. P.

doi:10.1001/jamanetworkopen.2020.26921

Cited by 97 publications

(56 citation statements)

References 42 publications

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“…This result has also been reported in a recent retrospective study using an intensive follow-up of recent improvements in treatment and imaging [12]. Furthermore, early detection, such as the detection of circulating tumor DNA, was reported to be signi cantly associated with reduction in RFS in patients with early BC [13]; however, we should carefully judge whether early detection of the presence of circulating tumor DNA leads to prolonged OS. Furthermore, our results showed that the duration of chemotherapy was signi cantly longer in patients with asymptomatic MBC than in those with symptomatic MBC.…”

Section: Discussionsupporting

confidence: 82%

Prognosis and Treatment of Asymptomatic Versus Symptomatic Metastatic Breast Cancer: A Multicenter Retrospective Study

Kuba

Maeda

Minami

et al. 2022

Preprint

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Background In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using any tumor marker or imaging tests. We aimed to determine whether differences in clinicopathological features, subtypes, prognosis, and treatment exist between asymptomatic and symptomatic MBCs. Methods We performed a multicenter, retrospective analysis of patients with MBC who visited our hospitals from 2008 to 2018. Patients were divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtypes: luminal (hormone receptor positive/hormone receptor negative/human epidermal growth factor receptor 2 (HER2) negative), HER2 (any hormone receptor/HER2 positive), and TN (hormone receptor negative/HER2 negative). Results Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts and TN patients in the asymptomatic group had longer post-recurrence survival (all cohorts: p < 0.001, TN: p = 0.01) and tended to have longer overall survival (all cohorts: p = 0.09, TN: p = 0.06) than those in the symptomatic group. In contrast, for the luminal and HER2 subtypes, post-recurrence survival was higher in the asymptomatic group than in the symptomatic group (luminal: p = 0.08, HER2: p = 0.09) but without significant difference in overall survival. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of post-recurrence survival. Regarding the luminal subtype, the asymptomatic group had longer durations of chemotherapy than the symptomatic group, with no significant difference observed in overall survival between the groups. Conclusion Asymptomatic and symptomatic MBCs require unique treatments due to prognostic differences.

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Section: Discussionsupporting

confidence: 82%

Prognosis and Treatment of Asymptomatic Versus Symptomatic Metastatic Breast Cancer: A Multicenter Retrospective Study

Kuba

Maeda

Minami

et al. 2022

Preprint

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“…The mutation burden was therefore associated with clinical parameters, representing the phenotype of cancer development [27,31]. We hypothesized that patients with "risk" clinical factors for breast cancer should harbor more mutations [32,33]. As predicted, our statistical analysis showed that an elevated ctDNA mutation burden was positively correlated with large primary tumor size, HER2(−) status, and poor survival outcome.…”

Section: Discussionmentioning

confidence: 70%

Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients

Sun

Lin

Chen

et al. 2021

Preprint

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Background Liquid biopsy through the detection of circulating tumor DNA (ctDNA) has potential advantages in cancer monitoring and prediction. However, most previous studies in this area were performed with a few hotspot genes, single time point detection, or insufficient sequencing depth.Methods In this study, we performed targeted next-generation sequencing (NGS) with a customized panel in metastatic breast cancer (MBC) patients. Fifty-four plasma samples were taken before chemotherapy and after the third course of treatment for detection and analysis. Paired lymphocytes were also included to eliminate clonal hematopoiesis (CH)-related alternatives.Results A total of 1182 nonsynonymous mutations on 419 genes were identified. More ctDNA mutations were detected in patients with tumors> 3cm (P = 0.035) and HER2(−) patients (P = 0.029). For a single gene, the distribution of ctDNA mutations was also correlated with clinical characteristics. Multivariate regression analysis revealed that HER2 status was significantly associated with mutation burden (OR 0.02, 95% CI 0–0.62, P = 0.025). The profiles of ctDNA mutations exhibited marked discrepancies between two time points, and baseline ctDNA was more sensitive and specific than that after chemotherapy. Finally, elevated ctDNA mutation level was positively correlated with poor survival (P < 0.001).Conclusion Mutations in ctDNA could serve as a potential biomarker for the evaluation and prediction, and guide the clinical management of MBC patients with chemotherapy.

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“…In metastatic pancreatic cancer, detectable ctDNA and high VAF was associated with worse overall survival [18,19,20]. Prognostic significance was observed in other solid tumors including colorectal cancer, breast cancer and prostate cancer [21][22][23]. Little is known about VAF and prognosis in biliary tract cancers.…”

Section: Discussionmentioning

confidence: 99%

Cell-Free Tumor DNA Dominant Clone Allele Frequency (DCAF) Is Associated With Poor Outcomes In Advanced Biliary Cancers Treated With Platinum-Based Chemotherapy

Junior

Majeed

Yin

et al. 2021

Preprint

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PURPOSEThis investigation sough to evaluate the prognostic value of pre-treatment ctDNA in metastatic biliary tract cancers (BTC) treated with platinum based first-line chemotherapy treatment.METHODSWe performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis we considered the detected gene with highest variant allele frequency (VAF) as the dominant clone allele frequency (DCAF). Results of ctDNA analysis were correlated with patients’ demographics, progression-free survival (PFS) and overall survival (OS).RESULTSThe median age of patients was 67 years (27-90). 54 (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma and six gallbladder cancers. 46 (68.6%) of the patients were treated with cisplatin plus gemcitabine, 16.4% of patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations while 15% of patients were treated on a clinical trial with gemcitabine and cisplatin plus additional agents (CX4945, PEGPH20 or nab-paclitaxel). TP53, KRAS, FGFR2, ARID1A, STK11 and IDH1 were the genes with highest frequency as DCAF. Median DCAF was 3% (0-97%). DCAF >3% was associated with worse OS (median OS: 10.8 vs. 18.8 months, p=0.032). Stratifying DCAF in quartiles, DCAF>10% was significantly related to worse PFS (median PFS: 3 months, p=0.014) and worse OS (median OS: 7.0 months, p=0.001). Each 1% increase in ctDNA was associated with a hazard ratio of 13.1 in OS when adjusting for subtypes, metastatic sites, size of largest tumor, age, sex, and CA19-9.CONCLUSIONDCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decrease survival probabilities.

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Association of Circulating Tumor DNA With Disease-Free Survival in Breast Cancer

Cited by 97 publications

References 42 publications

Prognosis and Treatment of Asymptomatic Versus Symptomatic Metastatic Breast Cancer: A Multicenter Retrospective Study

Prognosis and Treatment of Asymptomatic Versus Symptomatic Metastatic Breast Cancer: A Multicenter Retrospective Study

Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients

Cell-Free Tumor DNA Dominant Clone Allele Frequency (DCAF) Is Associated With Poor Outcomes In Advanced Biliary Cancers Treated With Platinum-Based Chemotherapy

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