Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay

H. Tanino, S. Oura, Robert M. Hoffman, T. Kubota, Toshiharu Furukawa, J. Arimoto, T. Yoshimasu, I. Hirai, T. Bessho, T. Suzuma, T. Sakurai, Y. Naito

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Recurrent breast cancer has a very poor response rate to chemotherapy. To understand the degree of acquisition of multidrug resistance in recurrent disease, 24 recurrent breast tumors and 127 primary tumors were evaluated and compared for chemosensitivity in the histoculture drug response assay (HDRA). The evaluation rate was 98.8%. The HDRA utilizes 3-dimensional culture of human tumors on collagen-gel rafts. Doxorubicin (DXR), 5-fluorouracil (5-FU) and mitomycin C (MMC) were tested as standard agents and cisplatin (CDDP) as a candidate agent on surgical specimen of breast cancer in the HDRA. In vitro drug exposure in the HDRA was for 7 days. At the end of the assay, tumor response was assessed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The mean inhibition rates of primary tumors vs. recurrent tumors were 57.9% and 38.6% for DXR (p<0.0005); 59.9% and 42.8% for MMC (p<0.01); 49.0% and 33.4% for 5-FU (p<0.01); and 34.5% and 16.0% for CDDP (p<0.005), respectively. The recurrent cases were pretreated clinically with CAF (cyclophosphamide, DXR and 5-FU), CEF (cyclophosphamide, epirubicin and 5-FU) or CMF (cyclophosphamide, methotrexate and 5-FU). In the CAF and CEF group, the HDRA sensitivity to CDDP was significantly lower in recurrent disease (p<0.005) than that of primary breast cancer suggesting that one agent can induce resistance to another. This is further suggested by the fact that 64.7% of the recurrent cases were resistant to all 4 agents tested as opposed to 27% of the primary cases and that only 5.9% of the recurrent cases were sensitive to three or more agents as opposed to 18% of the primary cases. The correlation of the HDRA results to clinical outcome in the study was 80.0% with 15 cases evaluated consisting of 5 true positives, 3 false positives, 7 true negatives and no false negatives. Thus, the HDRA gives useful clinical information, in particular for the specific individualized treatment design necessary to overcome the multidrug resistance problem of recurrent breast cancer.

Original languageEnglish
Pages (from-to)4083-4086
Number of pages4
JournalAnticancer Research
Volume21
Issue number6 A
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Multiple Drug Resistance
Fluorouracil
Breast Neoplasms
Pharmaceutical Preparations
Cyclophosphamide
Doxorubicin
Epirubicin
Mitomycin
Neoplasms
Methotrexate
Cisplatin
Collagen
Gels
Outcome Assessment (Health Care)
Drug Therapy

Keywords

  • Breast cancer
  • Chemosensitivity test
  • Histoculture drug response assay
  • Individualized chemotherapy
  • Multidrug resistance
  • Recurrent disease

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tanino, H., Oura, S., Hoffman, R. M., Kubota, T., Furukawa, T., Arimoto, J., ... Naito, Y. (2001). Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay. Anticancer Research, 21(6 A), 4083-4086.

Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay. / Tanino, H.; Oura, S.; Hoffman, Robert M.; Kubota, T.; Furukawa, Toshiharu; Arimoto, J.; Yoshimasu, T.; Hirai, I.; Bessho, T.; Suzuma, T.; Sakurai, T.; Naito, Y.

In: Anticancer Research, Vol. 21, No. 6 A, 2001, p. 4083-4086.

Research output: Contribution to journalArticle

Tanino, H, Oura, S, Hoffman, RM, Kubota, T, Furukawa, T, Arimoto, J, Yoshimasu, T, Hirai, I, Bessho, T, Suzuma, T, Sakurai, T & Naito, Y 2001, 'Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay', Anticancer Research, vol. 21, no. 6 A, pp. 4083-4086.
Tanino, H. ; Oura, S. ; Hoffman, Robert M. ; Kubota, T. ; Furukawa, Toshiharu ; Arimoto, J. ; Yoshimasu, T. ; Hirai, I. ; Bessho, T. ; Suzuma, T. ; Sakurai, T. ; Naito, Y. / Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay. In: Anticancer Research. 2001 ; Vol. 21, No. 6 A. pp. 4083-4086.
@article{59ce39050620486a8c657356f8d85478,
title = "Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay",
abstract = "Recurrent breast cancer has a very poor response rate to chemotherapy. To understand the degree of acquisition of multidrug resistance in recurrent disease, 24 recurrent breast tumors and 127 primary tumors were evaluated and compared for chemosensitivity in the histoculture drug response assay (HDRA). The evaluation rate was 98.8{\%}. The HDRA utilizes 3-dimensional culture of human tumors on collagen-gel rafts. Doxorubicin (DXR), 5-fluorouracil (5-FU) and mitomycin C (MMC) were tested as standard agents and cisplatin (CDDP) as a candidate agent on surgical specimen of breast cancer in the HDRA. In vitro drug exposure in the HDRA was for 7 days. At the end of the assay, tumor response was assessed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The mean inhibition rates of primary tumors vs. recurrent tumors were 57.9{\%} and 38.6{\%} for DXR (p<0.0005); 59.9{\%} and 42.8{\%} for MMC (p<0.01); 49.0{\%} and 33.4{\%} for 5-FU (p<0.01); and 34.5{\%} and 16.0{\%} for CDDP (p<0.005), respectively. The recurrent cases were pretreated clinically with CAF (cyclophosphamide, DXR and 5-FU), CEF (cyclophosphamide, epirubicin and 5-FU) or CMF (cyclophosphamide, methotrexate and 5-FU). In the CAF and CEF group, the HDRA sensitivity to CDDP was significantly lower in recurrent disease (p<0.005) than that of primary breast cancer suggesting that one agent can induce resistance to another. This is further suggested by the fact that 64.7{\%} of the recurrent cases were resistant to all 4 agents tested as opposed to 27{\%} of the primary cases and that only 5.9{\%} of the recurrent cases were sensitive to three or more agents as opposed to 18{\%} of the primary cases. The correlation of the HDRA results to clinical outcome in the study was 80.0{\%} with 15 cases evaluated consisting of 5 true positives, 3 false positives, 7 true negatives and no false negatives. Thus, the HDRA gives useful clinical information, in particular for the specific individualized treatment design necessary to overcome the multidrug resistance problem of recurrent breast cancer.",
keywords = "Breast cancer, Chemosensitivity test, Histoculture drug response assay, Individualized chemotherapy, Multidrug resistance, Recurrent disease",
author = "H. Tanino and S. Oura and Hoffman, {Robert M.} and T. Kubota and Toshiharu Furukawa and J. Arimoto and T. Yoshimasu and I. Hirai and T. Bessho and T. Suzuma and T. Sakurai and Y. Naito",
year = "2001",
language = "English",
volume = "21",
pages = "4083--4086",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "6 A",

}

TY - JOUR

T1 - Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay

AU - Tanino, H.

AU - Oura, S.

AU - Hoffman, Robert M.

AU - Kubota, T.

AU - Furukawa, Toshiharu

AU - Arimoto, J.

AU - Yoshimasu, T.

AU - Hirai, I.

AU - Bessho, T.

AU - Suzuma, T.

AU - Sakurai, T.

AU - Naito, Y.

PY - 2001

Y1 - 2001

N2 - Recurrent breast cancer has a very poor response rate to chemotherapy. To understand the degree of acquisition of multidrug resistance in recurrent disease, 24 recurrent breast tumors and 127 primary tumors were evaluated and compared for chemosensitivity in the histoculture drug response assay (HDRA). The evaluation rate was 98.8%. The HDRA utilizes 3-dimensional culture of human tumors on collagen-gel rafts. Doxorubicin (DXR), 5-fluorouracil (5-FU) and mitomycin C (MMC) were tested as standard agents and cisplatin (CDDP) as a candidate agent on surgical specimen of breast cancer in the HDRA. In vitro drug exposure in the HDRA was for 7 days. At the end of the assay, tumor response was assessed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The mean inhibition rates of primary tumors vs. recurrent tumors were 57.9% and 38.6% for DXR (p<0.0005); 59.9% and 42.8% for MMC (p<0.01); 49.0% and 33.4% for 5-FU (p<0.01); and 34.5% and 16.0% for CDDP (p<0.005), respectively. The recurrent cases were pretreated clinically with CAF (cyclophosphamide, DXR and 5-FU), CEF (cyclophosphamide, epirubicin and 5-FU) or CMF (cyclophosphamide, methotrexate and 5-FU). In the CAF and CEF group, the HDRA sensitivity to CDDP was significantly lower in recurrent disease (p<0.005) than that of primary breast cancer suggesting that one agent can induce resistance to another. This is further suggested by the fact that 64.7% of the recurrent cases were resistant to all 4 agents tested as opposed to 27% of the primary cases and that only 5.9% of the recurrent cases were sensitive to three or more agents as opposed to 18% of the primary cases. The correlation of the HDRA results to clinical outcome in the study was 80.0% with 15 cases evaluated consisting of 5 true positives, 3 false positives, 7 true negatives and no false negatives. Thus, the HDRA gives useful clinical information, in particular for the specific individualized treatment design necessary to overcome the multidrug resistance problem of recurrent breast cancer.

AB - Recurrent breast cancer has a very poor response rate to chemotherapy. To understand the degree of acquisition of multidrug resistance in recurrent disease, 24 recurrent breast tumors and 127 primary tumors were evaluated and compared for chemosensitivity in the histoculture drug response assay (HDRA). The evaluation rate was 98.8%. The HDRA utilizes 3-dimensional culture of human tumors on collagen-gel rafts. Doxorubicin (DXR), 5-fluorouracil (5-FU) and mitomycin C (MMC) were tested as standard agents and cisplatin (CDDP) as a candidate agent on surgical specimen of breast cancer in the HDRA. In vitro drug exposure in the HDRA was for 7 days. At the end of the assay, tumor response was assessed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The mean inhibition rates of primary tumors vs. recurrent tumors were 57.9% and 38.6% for DXR (p<0.0005); 59.9% and 42.8% for MMC (p<0.01); 49.0% and 33.4% for 5-FU (p<0.01); and 34.5% and 16.0% for CDDP (p<0.005), respectively. The recurrent cases were pretreated clinically with CAF (cyclophosphamide, DXR and 5-FU), CEF (cyclophosphamide, epirubicin and 5-FU) or CMF (cyclophosphamide, methotrexate and 5-FU). In the CAF and CEF group, the HDRA sensitivity to CDDP was significantly lower in recurrent disease (p<0.005) than that of primary breast cancer suggesting that one agent can induce resistance to another. This is further suggested by the fact that 64.7% of the recurrent cases were resistant to all 4 agents tested as opposed to 27% of the primary cases and that only 5.9% of the recurrent cases were sensitive to three or more agents as opposed to 18% of the primary cases. The correlation of the HDRA results to clinical outcome in the study was 80.0% with 15 cases evaluated consisting of 5 true positives, 3 false positives, 7 true negatives and no false negatives. Thus, the HDRA gives useful clinical information, in particular for the specific individualized treatment design necessary to overcome the multidrug resistance problem of recurrent breast cancer.

KW - Breast cancer

KW - Chemosensitivity test

KW - Histoculture drug response assay

KW - Individualized chemotherapy

KW - Multidrug resistance

KW - Recurrent disease

UR - http://www.scopus.com/inward/record.url?scp=0035569237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035569237&partnerID=8YFLogxK

M3 - Article

C2 - 11911296

AN - SCOPUS:0035569237

VL - 21

SP - 4083

EP - 4086

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 6 A

ER -