Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies

被引：192

作者：

Wolf, Denise M. ^{[1
]}

Yau, Christina ^{[2
]}

Wulfkuhle, Julia ^{[3
]}

Brown-Swigart, Lamorna ^{[1
]}

Gallagher, Rosa, I ^{[3
]}

Lee, Pei Rong Evelyn ^{[1
]}

Zhu, Zelos ^{[2
]}

Magbanua, Mark J. ^{[1
]}

Sayaman, Rosalyn ^{[1
]}

O'Grady, Nicholas ^{[2
]}

Basu, Amrita ^{[2
]}

Delson, Amy ^{[4
]}

Coppe, Jean Philippe ^{[1
]}

Lu, Ruixiao ^{[5
]}

Braun, Jerome ^{[5
]}

Asare, Smita M. ^{[5
]}

Sit, Laura ^{[2
]}

Matthews, Jeffrey B. ^{[2
]}

Perlmutter, Jane ^{[6
]}

Hylton, Nola ^{[7
]}

Liu, Minetta C. ^{[8
]}

Pohlmann, Paula ^{[9
]}

Symmans, W. Fraser ^{[10
]}

Rugo, Hope S. ^{[11
]}

Isaacs, Claudine ^{[12
]}

DeMichele, Angela M. ^{[13
]}

Yee, Douglas ^{[14
]}

Berry, Donald A. ^{[15
]}

Pusztai, Lajos ^{[16
]}

Petricoin, Emanuel F. ^{[3
]}

Hirst, Gillian L. ^{[2
]}

Esserman, Laura J. ^{[2
]}

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

机构：

[1] Univ Calif San Francisco, Dept Lab Med, 2340 Sutter St, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA

[3] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA

[4] Univ Calif San Francisco, Breast Sci Advocacy Core, San Francisco, CA 94143 USA

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

[6] Gemini Grp, Ann Arbor, MI 48107 USA

[7] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA

[8] Mayo Clin, Dept Surg, Rochester, MN 55905 USA

[9] Georgetown Univ, MedStar Georgetown Univ Hosp, Washington, DC 20057 USA

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

[11] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94158 USA

[12] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA

[13] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[14] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA

[15] Berry Consultants LLC, Austin, TX 78746 USA

[16] Yale Univ, Yale Sch Med, New Haven, CT 06510 USA

来源：

CANCER CELL | 2022年 / 40卷 / 06期

关键词：

STANDARD NEOADJUVANT CHEMOTHERAPY; ADAPTIVE RANDOMIZATION; TREATMENT DECISIONS; 70-GENE SIGNATURE; CARBOPLATIN; TRIAL; AID;

D O I：

10.1016/j.ccell.2022.05.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess the predictive performance of mechanism-of-action biomarkers from similar to 990 patients treated with 10 regimens targeting diverse biology. We explore >11 subtyping schemas and identify treatment-subtype pairs maximizing the pathologic complete response (pCR) rate over the population. The best performing schemas incorporate Immune, DNA repair, and HER2/Luminal phenotypes. Subsequent treatment allocation increases the overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. pCR gains from reclassification and improved patient selection are highest in HR+ subsets (>15%). As new treatments are introduced, the subtyping schema determines the minimum response needed to show efficacy. This data platform provides an unprecedented resource and supports the usage of response-based subtypes to guide future treatment prioritization.

引用

页码：609 / +

页数：22

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