J Breast Cancer. 2007 Sep;10(3):193-198. Korean.
Published online Sep 30, 2007.
Copyright © 2007 Korean Breast Cancer Society
Original Article

Can the Histoculture Drug Response Assay Predict the Clinical Results of Chemotherapy in Breast Cancer?

Yong Sik Jung, Young Up Cho,1 Young Jin Suh,2 Jeong Soo Kim,2 Se-Jeong Oh,2 Cheol Wan Lim,3 Moon Bo Kim,4 and Heung Kyu Park5
    • Department of Surgery, Ajou University, School of Medicine, Suwon, Korea.
    • 1Department of Surgery, Inha University, College of Medicine, Incheon, Korea.
    • 2Department of Surgery, the Catholic University of Korea, College of Medicine, Seoul, Korea.
    • 3Department of Surgery, Soonchunhyang University, College of Medicine, Seoul, Korea.
    • 4MetaBio Incorporated, Seoul, Korea.
    • 5Department of Surgery, Gachon University of Medical and Science, Incheon, Korea.
Received May 21, 2007; Accepted July 24, 2007.

Abstract

Purpose

The behavior of invasive carcinomas in human can be very varied with different individual responses to chemotherapy. Individualization is crucial to the optimization of chemotherapy. Therefore, the prediction of a tumor's sensitivity to anticancer agents has been the subject of intensive investigation. In order to investigate the pathobiology of breast cancer, it is necessary to maintain or recreate the characteristics of the three-dimensional architecture of the tissues in culture. In this study, we have evaluated the relationship between the Histoculture Drug Response Assay (HDRA) assessment and chemotherapy responses in breast cancer patients.

Methods

Tumor specimens from 30 patients with breast cancer were evaluated using the HDRA. Tumor tissues were cultured on gelfoam sponge gel in 24-well plates, followed by treatment with a variety of chemotherapeutic agents. All treatments were conducted in triplicate. The sensitivity of a chemotherapy regimen was defined as a tumor inhibition ate (IR) in excess of 30%. Neoadjuvant or palliative chemotherapy for patients, using anthracycline or taxane, was conducted on the basis of the established protocols. The responses to treatments were compared with the results of the HDRA.

Results

The mean IR for the combinations of doxorubicin and docetaxel and for FAC and AC were 48, 45, and 36%, respectively. The above partial rate of response to chemotherapy was 81.1%. The sensitivity and specificity of the HDRA assessment, with a 30% inhibition rate, were 81.5 and 66.7%, respectively. The positive and negative response prediction values were 91.7 and 44.4%, respectively. The responses to treatments and the results of the HDRA assessment were not correlated with the expressions of the hormonal receptor or c-erbB2.

Conclusion

In cases in which the inhibition rate is in excess of 30%, the HDRA assessment yielded a high positive response prediction value. The sensitivity to chemotherapy, as determined by the HDRA, appears to be a good guide for selection in breast cancer patients. Thus the results presented herein should be integrated into future research on the subject.

Keywords
Breast cancer; Chemotherapy; Histoculture Drug Response Assay (HDRA)

Figures

Fig 1
Schematic process of 3 dimensional histoculture drug response assay.

Fig 2
Average inhibiton rate in 3-dimensional histoculture drug response assay.

ADR=adriamycin; CTX=cyclophosphamide; FAC=combination of 5FU, adriamycin, cyclophosphamide; AC=combination of adriamycin, cyclophosphamide; AD=combination of adriamycin, docetaxel.

Tables

Table 1
Concentrations and referencces of anti-cancer drugs in Histoculture Drug Response Assay

Table 2
Regimens and mean dosage of chemotherapy were treated to patients

Table 3
Response evaluation criteria in solid tumors (RECIST)

Table 4
Clinico-pathologic characteristics of patients

Table 5
Correlation between result of HDRA and response to adriamycin with or without docetaxel combination

References

    1. Kern DH, Wiesenthal LM. Highly specific prediction of antineoplastic drug resistance with an in vitro assay using suprapharmacologic drug exposure. J Natl Cancer Inst 1990;82:582–588.
    1. Hoffman RM. In vitro assays for chemotherapy sensitivity. Crit Rev Oncol Hematol 1993;15:99–111.
    1. Kim JB, Stein R, O'Hare MJ. Three-dimensional in vitro tissue culture models of breast cancer-a review. Breast Cancer Res Treat 2004;85:281–291.
    1. Furukawa T, Kubota T, Hoffman RM. Clinical applications of the histoculture drug response assay. Clin Cancer Res 1995;1:305–311.
    1. Furukawa T, Kubota T, Watanabe M, Takahara T, Yamaguchi H, Takeuchi T, et al. High in vitro-in vivo correlation of drug response using sponge-gel-supported three-dimensional histoculture and the MTT end point. Int J Cancer 1992;51:489–498.
    1. Hoffman RM. To do tissue culture in two or three dimensions? that is the question. Stem Cells 1993;11:105–111.
    1. Sourla A, Doillon C, Koutsilieris M. Three-dimensional type I collagen gel system containing MG-63 osteoblasts-like cells as a model for studying local bone reaction caused by metastatic cancer cells. Anticancer Res 1996;16:2773–2780.
    1. Jacquot J, Spilmont C, Burlet H, Fuchey C, Buisson AC, Tournier JM, et al. Glandular-like morphogenesis and secretory activity of human tracheal gland cells in a three-dimensional collagen gel matrix. J Cell Physiol 1994;161:407–418.
    1. Kang HJ, Ko CD, Yoon HS, Kim MB, Ahn SH. The reliability of histoculture drug response assay (HDRA) in chemosensitivity tests for breast cancer. Cancer Res Treat 2001;33:392–398.
    1. Vescio RA, Connors KM, Kubota T, Hoffman RM. Correlation of histology and drug response of human tumors grown in native-state three-dimensional histoculture and in nude mice. Proc Natl Acad Sci USA 1991;88:5163–5166.
    1. Singh B, Li R, Xu L, Poluri A, Pastel S, Shaha AR, et al. Prediction of survival in patients with head and neck cancer using the histoculture drug response assay. Head Neck 2002;24:437–442.
    1. Yoshimasu T, Oura S, Maebeya S, Tanino H, Bessho T, Arimoto J, et al. Histoculture drug response assay on non-small cell lung cancer. Gan To Kagaku Ryoho 2000;27:717–722.
    1. Ariyoshi Y, Shimahar M, Tanigawa N. Study on chemosensitivity of oral squamous cell carcinomas by histoculture drug respose assay. Oral Oncol 2003;39:701–707.
    1. Hirano Y, Ushiyama T, Suzuki K, Fujita K. Clinical application of an in vitro chemosensitivity test, the Histoculture Drug Response Assay, to urological cancers: wide distribution of inhibition rates in bladder cancer and renal cell cancer. Urol Res 1999;27:483–488.
    1. Ohie S, Udagawa Y, Kozu A, Komuro Y, Aoki D, Nozawa S, et al. Cisplatin sensitivity of ovarian cancer in the histoculture drug response assay correlates to clinical response to combination chemotherapy with cisplatin, doxorubicin and cyclophosphamide. Anticancer Res 2000;20:2049–2054.

Metrics
Share
Figures

1 / 2

Tables

1 / 5

PERMALINK