Predictors of success in establishing orthotopic patient-derived xenograft models of triple negative breast cancer

被引：7

作者：

Echeverria, Gloria, V ^{[1
,7
,8
]}

Cai, Shirong ^{[1
]}

Tu, Yizheng ^{[1
]}

Shao, Jiansu ^{[1
]}

Powell, Emily ^{[1
]}

Redwood, Abena B. ^{[1
]}

Jiang, Yan ^{[1
]}

McCoy, Aaron ^{[1
]}

Rinkenbaugh, Amanda L. ^{[1
]}

Lau, Rosanna ^{[2
]}

Trevarton, Alexander J. ^{[2
]}

Fu, Chunxiao ^{[2
]}

Gould, Rebekah ^{[2
]}

Ravenberg, Elizabeth E. ^{[3
]}

Huo, Lei ^{[2
]}

Candelaria, Rosalind ^{[4
]}

Santiago, Lumarie ^{[4
]}

Adrada, Beatriz E. ^{[4
]}

Lane, Deanna L. ^{[3
]}

Rauch, Gaiane M. ^{[5
]}

Yang, Wei T. ^{[3
]}

White, Jason B. ^{[3
]}

Chang, Jeffrey T. ^{[6
]}

Moulder, Stacy L. ^{[3
]}

Symmans, W. Fraser ^{[2
]}

Hilsenbeck, Susan G. ^{[7
]}

Piwnica-Worms, Helen ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA

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

[3] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Breast Imaging, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Abdominal Imaging, Houston, TX 77030 USA

[6] Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA

[7] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA

[8] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

来源：

NPJ BREAST CANCER | 2023年 / 9卷 / 01期

基金：

美国国家卫生研究院;

关键词：

NEOADJUVANT CHEMOTHERAPY; ENDOCRINE-THERAPY; HETEROGENEITY; METASTASIS; SIGNATURES; DISEASE;

D O I：

10.1038/s41523-022-00502-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. We established orthotopic PDX models of triple negative breast cancer (TNBC) from the primary breast tumors of patients prior to and following neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a total of 269 fine needle aspirates (FNAs) from 217 women, generating a total of 62 PDX models (overall success-rate = 23%). Success of PDX engraftment was generally higher from those cancers that proved to be treatment-resistant, whether poorly responsive to AC as determined by ultrasound measurements mid-NACT (p = 0.063), RCB II/III status after NACT (p = 0.046), or metastatic relapse within 2 years of surgery (p = 0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT tumors revealed no significant association with PDX engraftment rate (p = 0.877). Finally, we developed a statistical model predictive of PDX engraftment using percent Ki67 positive cells in the patient's diagnostic biopsy, positive lymph node status at diagnosis, and low volumetric reduction of the patient's tumor following AC treatment. This novel bank of 62 PDX models of TNBC provides a valuable resource for biomarker discovery and preclinical therapeutic trials aimed at improving neoadjuvant response rates for patients with TNBC.

引用

页数：9

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