The Role of Biological Markers as Predictors of Response to Preoperative Chemotherapy in Large Primary Breast Cancer

Cocquyt, Véronique; Schelfhout, Vera; Blondeel, Phillip; Depypere, Herman; Daems, K; Serreyn, Rudolphe; Praet, Marleen; Belle, S.J.P. Van

doi:10.1385/mo:20:3:221

Cited by 17 publications

(19 citation statements)

References 31 publications

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“…On the other hand, it has been shown that some chemotherapeutic agents are less effective in patients with ER? tumors than those with ER-tumors [5,[8][9][10]24]. However, despite the fact that the involvement of ER in drug resistance to chemotherapy has been known for many years, very few studies have investigated the underlying mechanisms and potential strategies to reverse the ER-mediated chemoresistance [24,34,35].…”

Section: Discussionmentioning

confidence: 99%

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Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Sui

Jiang

Hinsch

et al. 2009

Breast Cancer Res Treat

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Cumulative data suggest that some chemotherapeutic agents may be less effective in estrogen receptor alpha positive (ER+) breast tumors than ER negative (ER-) tumors, which has raised a clinically relevant question as to how to reverse this ER-mediated chemoresistance in ER+ breast tumors. This study is to investigate the possible influence of estrogen receptor alpha (ERalpha) on the therapeutic effects of vinblastine and vinorelbine on breast cancer cells and explore whether combination of anti-estrogen agent fulvestrant (ICI 182, 780) may enhance the sensitivity of ERalpha+ cells to these chemotherapeutic agents. Through comparing ER+ with ER- human breast tumor cells or through stable transfection of an ERalpha expression vector into ER negative human breast cancer BCap37 cells, a series of assays were applied to determine the sensitivity of ER+ and ER- breast tumor cells to vinblastine and vinorelbine in the presence or absence of 17-beta-estradiol and/or fulvestrant. 17-beta-Estradiol showed no effect on the sensitivity of ER- MDA-MB-468 and BCap37 cells to the treatment of vincristine or vinblastine, but it significantly reduced the sensitivity of ER+ T47D cells and BCap37 cells expressing ERalpha to the two drugs mentioned. Further analyses show that ERalpha has little effect on vinca alkaloids-induced mitotic arrest, but dramatically affects their ability to induce tumor cell apoptosis. Moreover, through a series of assays, we also demonstrated that the combination of fulvestrant, a selective ER down-regulator, could reverse the resistance of ER+ breast tumor cells to vinca alkaloids and even produce synergistic effects. The findings obtained from this study have provided important evidence that expression and subsequent activation of ERalpha are associated with resistance of breast cancer cells to vinca alkaloids. This study also suggested that the combination of anti-estrogen agents, such as fulvestrant, might be a novel strategy to reverse ER-mediated chemoresistance or sensitize ER+ breast tumors to vinca alkaloids and possibly other chemotherapeutic agents.

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Section: Discussionmentioning

confidence: 99%

“…tumors than those with ER-tumors. These findings indicate that ER status may play an important role in determining the sensitivity of breast tumors to chemotherapy, although the underlying mechanisms are not entirely clear [5,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Sui

Jiang

Hinsch

et al. 2009

Breast Cancer Res Treat

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show abstract

“…Specifically, it has been observed that some chemotherapeutic agents may be less effective in patients with ER+ tumors than those with ERÀ tumors. These findings indicate that ER status may play an important role in determining the sensitivity of breast tumors to chemotherapy, although the mechanisms underlying ER-mediated drug resistance are not entirely clear (8,(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor α Mediates Breast Cancer Cell Resistance to Paclitaxel through Inhibition of Apoptotic Cell Death

et al. 2007

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Estrogen receptors (ER) are expressed in f65% of human breast cancer. Cumulative data from clinical trials and retrospective analyses suggest that some chemotherapeutic agents may be less effective in patients with ER-positive (ER+) tumors than those with ER-negative (ERÀ) tumors. Paclitaxel is an active agent used in breast cancer chemotherapy. To investigate the possible influence of ER on the therapeutic efficacy of paclitaxel and its underlying mechanism, we established several isogenic ER+ cell lines by stable transfection of ERA expression vectors into ERÀ breast cancer BCap37 cells. We showed that 17-B estradiol significantly reduces the overall cytotoxicity of paclitaxel in BCap37-expressing ERA but has no influence on the ERÀ parental cells. Further analyses indicate that expression of ERA in BCap37 cells mainly interferes with paclitaxel-induced apoptotic cell death, without affecting paclitaxel-induced microtubule bundling and mitotic arrest. Moreover, we found that the addition of ICI 182,780 (Fulvestrant), a selective ER down-regulator, could completely reverse the resistance of ER+ BCap37 cells to paclitaxel. These findings showed that ERA-mediated breast tumor cell resistance to paclitaxel was through selective inhibition of paclitaxel-induced tumor cell apoptosis. Additionally, the combination of ICI 182,780 also sensitizes MCF-7 and T47D cell lines to the treatment of paclitaxel, which further confirmed the correlation between ERA and drug resistance in ER+ tumor cells. The results obtained from this study provide useful information for understanding ERmediated resistance to paclitaxel and possibly other antineoplastic agents. [Cancer Res 2007;67(11):5337-44]

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“…Most recently, several neoadjuvant trials suggest that ERα-tumors are more sensitive to chemotherapy than ERα+ tumors. [22][23][24][25][26][27] In addition, the world overview of adjuvant chemotherapy trials for breast cancer conducted by the Early Breast Cancer Collaborative Group supports the hypothesis that patients with ERα-breast cancer experience more benefit from adjuvant chemotherapy than patients with ERα+ disease. 28 The biological basis for the potential relationship between ERα and the effectiveness of adjuvant therapy remains uncertain, nonetheless differences in cell cycle regulation between ERα+ and ERα-tumors have, for a long time, been a central feature of most explanations that have been proffered.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

Dougherty¹,

Schumaker²,

Jordan³

et al. 2004

Cancer Biology & Therapy

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ACKNOWLEDGEMENTS Research Paper Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer ABSTRACTA 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 paclitaxelinduced 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.

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The Role of Biological Markers as Predictors of Response to Preoperative Chemotherapy in Large Primary Breast Cancer

Cited by 17 publications

References 31 publications

Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Estrogen Receptor α Mediates Breast Cancer Cell Resistance to Paclitaxel through Inhibition of Apoptotic Cell Death

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

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