Estrogen receptor expression and sensitivity to paclitaxel in breast cancer

Michele K. Dougherty, Lisa M. Schumaker, V. Craig Jordan, Wade V. Welshons, Edward M. Curran, Matthew J. Ellis, Dorraya El-Ashry

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A retrospective analysis of CALGB trial 9344 suggested paclitaxel administration following cyclophosphamide and doxorubicin adjuvant chemotherapy is most beneficial for patients with ERα negative (ERα-) breast cancer. Since the cytotoxic effects of paclitaxel are cell cycle dependent, we postulated that the relationship between ERα and the effectiveness of adjuvant paclitaxel reflects the observation that ERα positive (ERα+) breast cancers proliferate more slowly than ERα- breast cancers. Three in vitro models (MCF-7, T47D and ZR-75) were examined to compare growth rates and paclitaxel-induced apoptosis in ERα+ and ERα- clones of the same, originally ERα+ cell line. For the T47D and ZR-75 cell lines, loss of ERα was associated with a decrease in doubling time and an increase in paclitaxel sensitivity. However, when cell culture conditions were altered to achieve equivalent cell proliferation rates, no difference in paclitaxel sensitivity was observed. Similarly, an ERα- clone of MCF-7 cells that did not exhibit an enhanced growth rate compared to its ERα+ counterpart also did not show increased paclitaxel sensitivity. The combined apoptotic effects of tamoxifen and paclitaxel on MCF-7 cells were not synergistic or even clearly additive. In these in vitro models, the effectiveness of paclitaxel correlated more closely with growth rate than ERα expression. These data suggest that measurements of tumor proliferation may provide more accurate predictive markers for the benefits of adjuvant paclitaxel than ERα analysis.

Original languageEnglish
Pages (from-to)460-467
Number of pages8
JournalCancer Biology and Therapy
Volume3
Issue number5
StatePublished - May 1 2004
Externally publishedYes

Fingerprint

Paclitaxel
Estrogen Receptors
Breast Neoplasms
MCF-7 Cells
Growth
Clone Cells
Cell Line
Tamoxifen
Adjuvant Chemotherapy
Doxorubicin
Cyclophosphamide
Cell Cycle
Cell Culture Techniques
Cell Proliferation
Apoptosis

Keywords

  • Apoptosis
  • Breast
  • Cell cycle
  • Estrogen receptor
  • Paclitaxel
  • Taxane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dougherty, M. K., Schumaker, L. M., Jordan, V. C., Welshons, W. V., Curran, E. M., Ellis, M. J., & El-Ashry, D. (2004). Estrogen receptor expression and sensitivity to paclitaxel in breast cancer. Cancer Biology and Therapy, 3(5), 460-467.

Estrogen receptor expression and sensitivity to paclitaxel in breast cancer. / Dougherty, Michele K.; Schumaker, Lisa M.; Jordan, V. Craig; Welshons, Wade V.; Curran, Edward M.; Ellis, Matthew J.; El-Ashry, Dorraya.

In: Cancer Biology and Therapy, Vol. 3, No. 5, 01.05.2004, p. 460-467.

Research output: Contribution to journalArticle

Dougherty, MK, Schumaker, LM, Jordan, VC, Welshons, WV, Curran, EM, Ellis, MJ & El-Ashry, D 2004, 'Estrogen receptor expression and sensitivity to paclitaxel in breast cancer', Cancer Biology and Therapy, vol. 3, no. 5, pp. 460-467.
Dougherty MK, Schumaker LM, Jordan VC, Welshons WV, Curran EM, Ellis MJ et al. Estrogen receptor expression and sensitivity to paclitaxel in breast cancer. Cancer Biology and Therapy. 2004 May 1;3(5):460-467.
Dougherty, Michele K. ; Schumaker, Lisa M. ; Jordan, V. Craig ; Welshons, Wade V. ; Curran, Edward M. ; Ellis, Matthew J. ; El-Ashry, Dorraya. / Estrogen receptor expression and sensitivity to paclitaxel in breast cancer. In: Cancer Biology and Therapy. 2004 ; Vol. 3, No. 5. pp. 460-467.
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