Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030

被引：19

作者：

Parsons, H. A. ^{[1
,2
,3
,17
]}

Blewett, T. ^{[4
]}

Chu, X. ^{[5
]}

Sridhar, S. ^{[4
]}

Santos, K. ^{[1
]}

Xiong, K. ^{[4
]}

Abramson, V. G. ^{[6
]}

Patel, A. ^{[1
]}

Cheng, J. ^{[4
]}

Brufsky, A. ^{[7
]}

Rhoades, J. ^{[4
]}

Force, J. ^{[8
]}

Liu, R. ^{[4
]}

Traina, T. A. ^{[9
]}

Carey, L. A. ^{[10
]}

Rimawi, M. F. ^{[11
]}

Miller, K. D. ^{[12
]}

Stearns, V. ^{[13
]}

Specht, J. ^{[14
]}

Falkson, C. ^{[15
,20
]}

Burstein, H. J. ^{[1
,2
,3
]}

Wolff, A. C.

Winer, E. P. ^{[1
,2
,19
]}

Tayob, N. ^{[5
]}

Krop, I. E. ^{[1
,2
,3
,19
]}

Markrigiorgos, G. M. ^{[16
]}

Golub, T. R. ^{[4
]}

Mayer, E. L. ^{[1
,2
,3
,17
]}

Adalsteinsson, V. A. ^{[4
,18
]}

机构：

[1] Dana Farber Canc Inst, Med Oncol, Boston, MA USA

[2] Dana Farber Brigham Canc Ctr, Breast Oncol Program, Boston, MA USA

[3] Harvard Med Sch, Boston, MA USA

[4] Broad Inst MIT & Harvard, Cambridge, MA USA

[5] Dana Farber Canc Inst, Data Sci, Boston, MA USA

[6] Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[7] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA

[8] Duke Canc Ctr, Durham, NC USA

[9] Mem Sloan Kettering Canc Ctr, New York, NY USA

[10] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[11] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX USA

[12] Indiana Univ, Melvin & Bren Simon Comprehens Canc Ctr, Indianapolis, IN USA

[13] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[14] Seattle Canc Care Alliance, Seattle, WA USA

[15] Univ Alabama Birmingham, Birmingham, AL USA

[16] Dana Farber Canc Inst, Radiat Oncol, Boston, MA USA

[17] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA

[18] Dana Farber Canc Inst, 75 Ames St, Cambridge, MA 02142 USA

[19] Yale Canc Ctr, New Haven, CT USA

[20] Univ Rochester, Wilmot Canc Inst, Rochester, NY USA

来源：

ANNALS OF ONCOLOGY | 2023年 / 34卷 / 10期

关键词：

circulating tumor DNA; triple-negative breast cancer; biomarkers; recurrence; minimal residual disease; SURVIVAL; RISK;

D O I：

10.1016/j.annonc.2023.08.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy.Patients and methods: We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence.Results: Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 nonresponders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 x 10(4) (range 7.9 x 10(-7)-4.9 x 10(1)). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12.Conclusions: Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in nonresponders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes.

引用

页码：899 / 906

页数：8

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