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

共 20 条

[1] Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution [J].

Abbosh, Christopher ;

Birkbak, Nicolai J. ;

Wilson, Gareth A. ;

Jamal-Hanjani, Mariam ;

Constantin, Tudor ;

Salari, Raheleh ;

Le Quesne, John ;

Moore, David A. ;

Veeriah, Selvaraju ;

Rosenthal, Rachel ;

Marafioti, Teresa ;

Kirkizlar, Eser ;

Watkins, Thomas B. K. ;

McGranahan, Nicholas ;

Ward, Sophia ;

Martinson, Luke ;

Riley, Joan ;

Fraioli, Francesco ;

Al Bakir, Maise ;

Gronroos, Eva ;

Zambrana, Francisco ;

Endozo, Raymondo ;

Bi, Wenya Linda ;

Fennessy, Fiona M. ;

Sponer, Nicole ;

Johnson, Diana ;

Laycock, Joanne ;

Shafi, Seema ;

Czyzewska-Khan, Justyna ;

Rowan, Andrew ;

Chambers, Tim ;

Matthews, Nik ;

Turajlic, Samra ;

Hiley, Crispin ;

Lee, Siow Ming ;

Forster, Martin D. ;

Ahmad, Tanya ;

Falzon, Mary ;

Borg, Elaine ;

Lawrence, David ;

Hayward, Martin ;

Kolvekar, Shyam ;

Panagiotopoulos, Nikolaos ;

Janes, Sam M. ;

Thakrar, Ricky ;

Ahmed, Asia ;

Blackhall, Fiona ;

Summers, Yvonne ;

Hafez, Dina ;

Naik, Ashwini .

NATURE, 2017, 545 (7655) :446-+

[2] Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors [J].

Adalsteinsson, Viktor A. ;

Ha, Gavin ;

Freeman, Samuel S. ;

Choudhury, Atish D. ;

Stover, Daniel G. ;

Parsons, Heather A. ;

Gydush, Gregory ;

Reed, Sarah C. ;

Rotem, Denisse ;

Rhoades, Justin ;

Loginov, Denis ;

Livitz, Dimitri ;

Rosebrock, Daniel ;

Leshchiner, Ignaty ;

Kim, Jaegil ;

Stewart, Chip ;

Rosenberg, Mara ;

Francis, Joshua M. ;

Zhang, Cheng-Zhong ;

Cohen, Ofir ;

Oh, Coyin ;

Ding, Huiming ;

Polak, Paz ;

Lloyd, Max ;

Mahmud, Sairah ;

Helvie, Karla ;

Merrill, Margaret S. ;

Santiago, Rebecca A. ;

O'Connor, Edward P. ;

Jeong, Seong H. ;

Leeson, Rachel ;

Barry, Rachel M. ;

Kramkowski, Joseph F. ;

Zhang, Zhenwei ;

Polacek, Laura ;

Lohr, Jens G. ;

Schleicher, Molly ;

Lipscomb, Emily ;

Saltzman, Andrea ;

Oliver, Nelly M. ;

Marini, Lori ;

Waks, Adrienne G. ;

Harshman, Lauren C. ;

Tolaney, Sara M. ;

Van Allen, Eliezer M. ;

Winer, Eric P. ;

Lin, Nancy U. ;

Nakabayashi, Mari ;

Taplin, Mary-Ellen ;

Johannessen, Cory M. .

NATURE COMMUNICATIONS, 2017, 8

[3] Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence [J].

Coombes, Raoul Charles ;

Page, Karen ;

Salari, Raheleh ;

Hastings, Robert K. ;

Armstrong, Anne ;

Ahmed, Samreen ;

Ali, Simak ;

Cleator, Susan ;

Kenny, Laura ;

Stebbing, Justin ;

Rutherford, Mark ;

Sethi, Himanshu ;

Boydell, Anna ;

Swenerton, Ryan ;

Fernandez-Garcia, Daniel ;

Gleason, Kelly L. T. ;

Goddard, Katie ;

Guttery, David S. ;

Assaf, Zoe J. ;

Wu, Hsin-Ta ;

Natarajan, Prashanthi ;

Moore, David A. ;

Primrose, Lindsay ;

Dashner, Scott ;

Tin, Antony S. ;

Balcioglu, Mustafa ;

Srinivasan, Ramya ;

Shchegrova, Svetlana V. ;

Olson, Alexander ;

Hafez, Dina ;

Billings, Paul ;

Aleshin, Alexey ;

Rehman, Farah ;

Toghill, Bradley J. ;

Hills, Allison ;

Louie, Maggie C. ;

Lin, Cheng-Ho Jimmy ;

Zimmermann, Bernhard G. ;

Shaw, Jaqueline A. .

CLINICAL CANCER RESEARCH, 2019, 25 (14) :4255-4263

[4] Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [J].

Cortazar, Patricia ;

Zhang, Lijun ;

Untch, Michael ;

Mehta, Keyur ;

Costantino, Joseph P. ;

Wolmark, Norman ;

Bonnefoi, Herve ;

Cameron, David ;

Gianni, Luca ;

Valagussa, Pinuccia ;

Swain, Sandra M. ;

Prowell, Tatiana ;

Loibl, Sibylle ;

Wickerham, D. Lawrence ;

Bogaerts, Jan ;

Baselga, Jose ;

Perou, Charles ;

Blumenthal, Gideon ;

Blohmer, Jens ;

Mamounas, Eleftherios P. ;

Bergh, Jonas ;

Semiglazov, Vladimir ;

Justice, Robert ;

Eidtmann, Holger ;

Paik, Soonmyung ;

Piccart, Martine ;

Sridhara, Rajeshwari ;

Fasching, Peter A. ;

Slaets, Leen ;

Tang, Shenghui ;

Gerber, Bernd ;

Geyer, Charles E., Jr. ;

Pazdur, Richard ;

Ditsch, Nina ;

Rastogi, Priya ;

Eiermann, Wolfgang ;

von Minckwitz, Gunter .

LANCET, 2014, 384 (9938) :164-172

[5] Triple-negative breast cancer: Clinical features and patterns of recurrence [J].

Dent, Rebecca ;

Trudeau, Maureen ;

Pritchard, Kathleen I. ;

Hanna, Wedad M. ;

Kahn, Harriet K. ;

Sawka, Carol A. ;

Lickley, Lavina A. ;

Rawlinson, Ellen ;

Sun, Ping ;

Narod, Steven A. .

CLINICAL CANCER RESEARCH, 2007, 13 (15) :4429-4434

[6] Triple-Negative Breast Cancer [J].

Foulkes, William D. ;

Smith, Ian E. ;

Reis-Filho, Jorge S. .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (20) :1938-1948

[7] Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer [J].

Garcia-Murillas, Isaac ;

Chopra, Neha ;

Comino-Mendez, Inaki ;

Beaney, Matthew ;

Tovey, Holly ;

Cutts, Rosalind J. ;

Swift, Claire ;

Kriplani, Divya ;

Afentakis, Maria ;

Hrebien, Sarah ;

Walsh-Crestani, Giselle ;

Barry, Peter ;

Johnston, Stephen R. D. ;

Ring, Alistair ;

Bliss, Judith ;

Russell, Simon ;

Evans, Abigail ;

Skene, Anthony ;

Wheatley, Duncan ;

Dowsett, Mitch ;

Smith, Ian E. ;

Turner, Nicholas C. .

JAMA ONCOLOGY, 2019, 5 (10) :1473-1478

[8] Massively parallel enrichment of low-frequency alleles enables duplex sequencing at low depth [J].

Gydush, Gregory ;

Nguyen, Erica ;

Bae, Jin H. ;

Blewett, Timothy ;

Rhoades, Justin ;

Reed, Sarah C. ;

Shea, Douglas ;

Xiong, Kan ;

Liu, Ruolin ;

Yu, Fangyan ;

Leong, Ka Wai ;

Choudhury, Atish D. ;

Stover, Daniel G. ;

Tolaney, Sara M. ;

Krop, Ian E. ;

Love, J. Christopher ;

Parsons, Heather A. ;

Makrigiorgos, G. Mike ;

Golub, Todd R. ;

Adalsteinsson, Viktor A. .

NATURE BIOMEDICAL ENGINEERING, 2022, 6 (03) :257-+

[9] Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer [J].

Haffty, Bruce G. ;

Yang, Qifeng ;

Reiss, Michael ;

Kearney, Thomas ;

Higgins, Susan A. ;

Weidhaas, Joanne ;

Harris, Lyndsay ;

Hait, Willam ;

Toppmeyer, Deborah .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (36) :5652-5657

[10] Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer [J].

Liedtke, Cornelia ;

Mazouni, Chafika ;

Hess, Kenneth R. ;

Andre, Fabrice ;

Tordai, Attila ;

Mejia, Jaime A. ;

Symmans, W. Fraser ;

Gonzalez-Angulo, Ana M. ;

Hennessy, Bryan ;

Green, Marjorie ;

Cristofanilli, Massimo ;

Hortobagyi, Gabriel N. ;

Pusztai, Lajos .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (08) :1275-1281

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