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J Transl Med. 2016 May 3;14(1):112. doi: 10.1186/s12967-016-0855-3.

Testing chemotherapy efficacy in HER2 negative breast cancer using patient-derived spheroids.

Author information

1
SpheroTec GmbH, Am Klopferspitz 19, 82152, Martinsried, Germany.
2
Department of Obstetrics and Gynecology, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany.
3
Department of General, Visceral, and Transplantation Surgery, Hospital of the LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
4
Department of Gynecology and Obstetrics, Technical University Munich, Ismaninger Str. 22, 81675, Munich, Germany.
5
Klinikum Harlaching, Sanatoriumsplatz 2, 81545, Munich, Germany.
6
Klinikum Landshut, Robert-Koch-Str. 1, 8434, Landshut, Germany.
7
SpheroTec GmbH, Am Klopferspitz 19, 82152, Martinsried, Germany. barbara.mayer@med.uni-muenchen.de.
8
Department of General, Visceral, and Transplantation Surgery, Hospital of the LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. barbara.mayer@med.uni-muenchen.de.

Abstract

BACKGROUND:

Targeted anti-HER2 therapy has greatly improved the prognosis for many breast cancer patients. However, treatment for HER2 negative disease is currently still selected from a multitude of untargeted chemotherapeutic treatment options. A predictive test was developed using patient-derived spheroids to identify the most effective therapy for patients with HER2 negative breast cancer of all stages, for clinically relevant subgroups, as well as individual patients.

METHODS:

Tumor samples from 120 HER2 negative patients obtained through biopsy or surgical excision were tested in the breast cancer spheroid model using scaffold-free cell culture. Similarly, spheroids were also generated from established HER2 negative breast cancer cell lines T-47D, MCF7, HCC1143, and HCC1937 to compare treatment efficacy of heterogeneous cell populations from patient tumor tissue with homogeneous cell lines. Spheroids were treated in vitro with guideline-recommended compounds. Treatment mediated impact on cell survival was subsequently quantified using an ATP assay.

RESULTS:

Differences were observed in the metabolic activity of the untreated spheroids, whereby cell lines consistently achieved higher values compared to tissue spheroids (p < 0.001). A higher number of cells per spheroid correlated with a higher basal metabolic activity in tissue-derived spheroids (p < 0.01), while the opposite was observed for cell line spheroids (p < 0.01). Recurrent tumors showed a higher mean vitality (p < 0.01) compared to primary tumors. Except for taxanes, treatment efficacy for most tested compounds differed significantly between breast cancer tissue spheroids and breast cancer cell lines. Overall a high variability in treatment response in vitro was seen in the tissue spheroids regardless of the tested substances. A greater response to anthracycline/docetaxel was observed for hormone receptor negative samples (p < 0.01). A higher response to 5-FU (p < 0.01) and anthracycline (p < 0.05) was seen in high grade tumors. Smaller tumor size and negative lymph node status were both associated with a higher treatment efficacy to anthracycline treatment combined with 5-FU (cT1/2 vs cT3/4, p = 0.035, cN+ vs cN-, p < 0.05).

CONCLUSIONS:

The tissue spheroid model reflects current guideline treatment recommendations for HER2 negative breast cancer, whereas tested cell lines did not. This model represents a unique diagnostic method to select the most effective therapy out of several equivalent treatment options.

KEYWORDS:

Breast cancer; In vitro diagnostics; Personalized medicine; Preclinical treatment selection; Spheroid cell culture

PMID:
27142386
PMCID:
PMC4855689
DOI:
10.1186/s12967-016-0855-3
[Indexed for MEDLINE]
Free PMC Article

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