Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.

Tytuł:: Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.
Autorzy:: Cavallone L; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Aguilar-Mahecha A; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Lafleur J; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Brousse S; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Aldamry M; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Roseshter T; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Lan C; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Alirezaie N; Department of Human Genetics, McGill University, Montreal, QC, Canada.
Bareke E; Department of Human Genetics, McGill University, Montreal, QC, Canada.
Majewski J; Department of Human Genetics, McGill University, Montreal, QC, Canada.
Ferrario C; Department of Oncology, Jewish General Hospital, Montreal, QC, Canada.
Hassan S; Division of Surgical Oncology, Department of Surgery, Centre Hospitalier de L'Université de Montréal (CHUM), Montreal, QC, Canada.
Discepola F; Department of Radiology, Jewish General Hospital, Montreal, QC, Canada.
Seguin C; Department of Radiology, Jewish General Hospital, Montreal, QC, Canada.
Mihalcioiu C; Department of Oncology, McGill University, Montreal, QC, Canada.
Marcus EA; Cook County Hospital, Chicago, IL, USA.
Robidoux A; Division of Surgical Oncology, Department of Surgery, Centre Hospitalier de L'Université de Montréal (CHUM), Montreal, QC, Canada.
Roy JA; Hôpital du Sacré-Cœur de Montréal, Montreal, QC, Canada.
Pelmus M; Department of Pathology, Jewish General Hospital, Montreal, QC, Canada.
Basik M; Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada. .
Źródło:: Scientific reports [Sci Rep] 2020 Sep 07; Vol. 10 (1), pp. 14704. Date of Electronic Publication: 2020 Sep 07.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:: Circulating Tumor DNA/*genetics
Triple Negative Breast Neoplasms/*genetics
Chemotherapy, Adjuvant ; Circulating Tumor DNA/blood ; Female ; Gene Frequency ; Genes, p53 ; Humans ; Middle Aged ; Mutation Rate ; Neoadjuvant Therapy ; Prognosis ; Triple Negative Breast Neoplasms/blood ; Triple Negative Breast Neoplasms/diagnosis ; Triple Negative Breast Neoplasms/drug therapy
References:: Cortazar, P. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384, 164–172 (2014). (PMID: 10.1016/S0140-6736(13)62422-8)
Symmans, W. F. et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J. Clin. Oncol. 25, 4414–4422 (2007). (PMID: 10.1200/JCO.2007.10.6823)
Masuda, N. et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N. Engl. J. Med. 376, 2147–2159 (2017). (PMID: 10.1056/NEJMoa1612645)
Kuerer, H. M. et al. Nonoperative management for invasive breast cancer after neoadjuvant systemic therapy: conceptual basis and fundamental international feasibility clinical trials. Ann. Surg. Oncol. 24, 2855–2862 (2017). (PMID: 10.1245/s10434-017-5926-z)
Merker, J. D. et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J. Clin. Oncol. 36, 1631–1641 (2018). (PMID: 10.1200/JCO.2017.76.8671)
Siravegna, G., Marsoni, S., Siena, S. & Bardelli, A. Integrating liquid biopsies into the management of cancer. Nat. Rev. Clin. Oncol. 14, 531–548 (2017). (PMID: 10.1038/nrclinonc.2017.14)
Beaver, J. A. et al. Detection of cancer DNA in plasma of patients with early-stage breast cancer. Clin. Cancer Res. 20, 2643–2650 (2014). (PMID: 10.1158/1078-0432.CCR-13-2933)
Bettegowda, C. et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med. 6, 224ra24 (2014). (PMID: 10.1126/scitranslmed.3007094)
Riva, F. et al. Patient-specific circulating tumor DNA detection during neoadjuvant chemotherapy in triple-negative breast cancer. Clin. Chem. 63, 691–699 (2017). (PMID: 10.1373/clinchem.2016.262337)
Garcia-Murillas, I. et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci. Transl. Med. 7, 302ra133 (2015). (PMID: 10.1126/scitranslmed.aab0021)
Siravegna, G. et al. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat. Med. 21, 827 (2015). (PMID: 10.1038/nm0715-827b)
Siravegna, G. et al. Plasma HER2 (ERBB2) copy number predicts response to HER2-targeted therapy in metastatic colorectal cancer. Clin. Cancer Res. 25, 3046–3053 (2019). (PMID: 10.1158/1078-0432.CCR-18-3389)
Campone, M. et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2. Eur. J. Cancer 103, 147–154 (2018). (PMID: 10.1016/j.ejca.2018.08.002)
Aguilar-Mahecha, A. et al. The identification of challenges in tissue collection for biomarker studies: the Q-CROC-03 neoadjuvant breast cancer translational trial experience. Mod. Pathol. 30, 1567–1576 (2017). (PMID: 10.1038/modpathol.2017.82)
Cavallone, L. et al. A study of pre-analytical variables and optimization of extraction method for circulating tumor DNA measurements by digital droplet PCR. Cancer Epidemiol. Biomark. Prev. 28, 909–916 (2019). (PMID: 10.1158/1055-9965.EPI-18-0586)
Dawson, S.-J. et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med. 368, 1199–1209 (2013). (PMID: 10.1056/NEJMoa1213261)
Fribbens, C. et al. Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. Ann. Oncol. 29, 145–153 (2018). (PMID: 10.1093/annonc/mdx483)
Rothé, F. et al. Circulating tumor DNA in HER2-amplified breast cancer: a translational research substudy of the NeoALTTO phase III trial. Clin. Cancer Res. 25, 3581–3588 (2019). (PMID: 10.1158/1078-0432.CCR-18-2521)
Butler, T. M. et al. Circulating tumor DNA dynamics using patient-customized assays are associated with outcome in neoadjuvantly treated breast cancer. Cold Spring Harb. Mol. Case Stud. 5(2), a003772 (2019). (PMID: 10.1101/mcs.a003772)
Substance Nomenclature:: 0 (Circulating Tumor DNA)
Entry Date(s):: Date Created: 20200908 Date Completed: 20210311 Latest Revision: 20210907
Update Code:: 20240105
PubMed Central ID:: PMC7477566
DOI:: 10.1038/s41598-020-71236-y
PMID:: 32895401
: Czasopismo naukowe

Pełny tekst

Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline. Mutant allele frequency at baseline was associated with clinical characteristics. Levels drastically fell after one cycle of NAC, especially in patients whose tumors would go on to have a pathological complete response (pCR), but then rose significantly before surgery in patients with significant residual tumor at surgery (p = 0.0001). The detection of ctDNA early during treatment and also late at the end of NAC before surgery was strongly predictive of residual tumor at surgery, but its absence was less predictive of pCR, especially when only TP53 variants are considered. ctDNA detection at the end of neoadjuvant chemotherapy indicated significantly worse relapse-free survival (HR = 0.29 (95% CI 0.08-0.98), p = 0.046), and overall survival (HR = 0.27 95% CI 0.075-0.96), p = 0.043). Hence, individualized multi-variant ctDNA testing during and after NAC prior to surgery has prognostic and predictive value in early TNBC patients.

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