Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy

被引：85

作者：

Magbanua, Mark Jesus M. ^{[1
]}

Swigart, Lamorna Brown ^{[1
]}

Ahmed, Ziad ^{[1
]}

Sayaman, Rosalyn W. ^{[1
]}

Renner, Derrick ^{[2
]}

Kalashnikova, Ekaterina ^{[2
]}

Hirst, Gillian L. ^{[1
]}

Yau, Christina ^{[1
]}

Wolf, Denise M. ^{[1
]}

Li, Wen ^{[1
]}

Delson, Amy L. ^{[3
]}

Asare, Smita ^{[4
]}

Liu, Minetta C. ^{[2
,5
]}

Albain, Kathy ^{[6
]}

Chien, A. Jo ^{[1
]}

Forero-Torres, Andres ^{[7
]}

Isaacs, Claudine ^{[8
]}

Nanda, Rita ^{[9
]}

Tripathy, Debu ^{[10
]}

Rodriguez, Angel ^{[2
]}

Sethi, Himanshu ^{[2
]}

Aleshin, Alexey ^{[2
]}

Rabinowitz, Matthew ^{[2
]}

Perlmutter, Jane ^{[3
]}

Symmans, W. Fraser ^{[10
]}

Yee, Douglas ^{[11
]}

Hylton, Nola M. ^{[1
]}

Esserman, Laura J. ^{[1
]}

DeMichele, Angela M. ^{[12
]}

Rugo, Hope S. ^{[1
]}

van 't Veer, Laura J. ^{[1
]}

机构：

[1] Univ Calif San Francisco, San Francisco, CA 94143 USA

[2] Natera Inc, Austin, TX 78753 USA

[3] UCSF Breast Sci Advocacy Core, San Francisco, CA 94143 USA

[4] Quantum Leap Healthcare Collaborat, San Francisco, CA 94118 USA

[5] Mayo Clin, Rochester, MN 55905 USA

[6] Loyola Univ Chicago, Maywood, IL 60153 USA

[7] Univ Alabama Birmingham, Birmingham, AL 35233 USA

[8] Georgetown Univ, Washington, DC 20007 USA

[9] Univ Chicago, Chicago, IL 60637 USA

[10] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[11] Univ Minnesota, Minneapolis, MN 55455 USA

[12] Univ Penn, Philadelphia, PA 19104 USA

来源：

CANCER CELL | 2023年 / 41卷 / 06期

关键词：

ADAPTIVE RANDOMIZATION; SUBTYPE CLASSIFICATION; TREATMENT DECISIONS; 70-GENE SIGNATURE; EXPRESSION; SURVIVAL; CTDNA; AID;

D O I：

10.1016/j.ccell.2023.04.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemo-therapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.

引用

页码：1091 / +

页数：17

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