Expression of drug resistance proteins in breast cancer, in relation to chemotherapy

Sabine C. Linn, Herbert M. Pinedo, Jannette Van Ark-Otte, Paul Van Der Valk, Klaas Hoekman, Aafke H. Honkoop, Jan B. Vermorken, Giuseppe Giaccone

Research output: Contribution to journalArticle

Abstract

Drug resistance plays an important role in chemotherapy failure in breast cancer. We studied the expression of MDR1, MRP, LRP, DNA topoisomerases, p53 and Ki-67 in different groups of breast cancer patients in relation to chemotherapy. Tissues from 6 normal breasts and 20 primary operable, 40 locally advanced and 10 anthracycline-resistant metastatic breast cancers were assessed. Sequential samples of the same patient: were available from 17 patients with locally advanced breast cancer undergoing neo-adjuvant chemotherapy and in 7 metastatic patients undergoing paclitaxel treatment. Protein expression was investigated by immunohistochemistry. Significantly higher protein expression was observed for Pgp, Ki-67 and p53 in the locally advanced breast cancers than in primary operable breast cancers. No other significant differences in protein expression were found among the 3 breast cancer groups. Expression of none of the markers that could be assessed (Pgp, MRP, LRP, p53 and Ki-67) in locally advanced breast cancer had predictive value for pathological response. Interestingly, after chemotherapy a significant decrease in percentage of Ki-67 positive tumor cells was observed, whereas the other markers did not vary substantially. Furthermore, considering all breast cancer samples, a cumulative dose of doxorubicin >400 mg/m2 inversely correlated with Ki-67 positivity. However, 2 patients with a pathological complete remission had only 5-10% Ki67-positive tumor cells before chemotherapy, indicating that Ki67 negativity itself is not responsible for chemoresistance. In conclusion, none of the known proteins related to multidrug resistance predicted response to chemotherapy in breast cancer, and resistant clones left behind generally had a low proliferation rate.

Original languageEnglish (US)
Pages (from-to)787-795
Number of pages9
JournalInternational Journal of Cancer
Volume71
Issue number5
DOIs
StatePublished - 1997
Externally publishedYes

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Drug Resistance
Breast Neoplasms
Drug Therapy
Proteins
DNA Topoisomerases
Anthracyclines
Multiple Drug Resistance
Adjuvant Chemotherapy
Paclitaxel
Doxorubicin
Neoplasms
Breast
Clone Cells
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Linn, S. C., Pinedo, H. M., Van Ark-Otte, J., Van Der Valk, P., Hoekman, K., Honkoop, A. H., ... Giaccone, G. (1997). Expression of drug resistance proteins in breast cancer, in relation to chemotherapy. International Journal of Cancer, 71(5), 787-795. https://doi.org/10.1002/(SICI)1097-0215(19970529)71:5<787::AID-IJC16>3.0.CO;2-5

Expression of drug resistance proteins in breast cancer, in relation to chemotherapy. / Linn, Sabine C.; Pinedo, Herbert M.; Van Ark-Otte, Jannette; Van Der Valk, Paul; Hoekman, Klaas; Honkoop, Aafke H.; Vermorken, Jan B.; Giaccone, Giuseppe.

In: International Journal of Cancer, Vol. 71, No. 5, 1997, p. 787-795.

Research output: Contribution to journalArticle

Linn, SC, Pinedo, HM, Van Ark-Otte, J, Van Der Valk, P, Hoekman, K, Honkoop, AH, Vermorken, JB & Giaccone, G 1997, 'Expression of drug resistance proteins in breast cancer, in relation to chemotherapy', International Journal of Cancer, vol. 71, no. 5, pp. 787-795. https://doi.org/10.1002/(SICI)1097-0215(19970529)71:5<787::AID-IJC16>3.0.CO;2-5
Linn, Sabine C. ; Pinedo, Herbert M. ; Van Ark-Otte, Jannette ; Van Der Valk, Paul ; Hoekman, Klaas ; Honkoop, Aafke H. ; Vermorken, Jan B. ; Giaccone, Giuseppe. / Expression of drug resistance proteins in breast cancer, in relation to chemotherapy. In: International Journal of Cancer. 1997 ; Vol. 71, No. 5. pp. 787-795.
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