J Breast Cancer.  2007 Sep;10(3):193-198. 10.4048/jbc.2007.10.3.193.

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

• Jung YS
• Cho YU
• Suh YJ
• Kim JS
• Oh SJ
• Lim CW
• Kim MB
• Park HK

• KMID: 2175035
• DOI: http://doi.org/10.4048/jbc.2007.10.3.193

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 rate (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.

Keyword

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

MeSH Terms

Antineoplastic Agents
Breast Neoplasms*
Breast*
Doxorubicin
Drug Therapy*
Gelatin Sponge, Absorbable
Humans
Porifera
Sensitivity and Specificity
Antineoplastic Agents
Doxorubicin

Figure

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

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  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.

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