Home: Oncology Leader Commentary: Gershon Locker, MD

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Trials of first line Arimidex
Choosing first-line endocrine therapy in postmenopausal patients
Vasomotor symptoms and Arimidex
Mechanisms of resistance to endocrine therapy
Tamoxifen rechallenge versus Arimidex
Aromatase inhibitors when adjuvant tamoxifen is contraindicated
ATAC adjuvant trial: Arimidex vs Tamoxifen vs the Combination

Interview with Neil Love, MD from Breast Cancer Update for Medical Oncologists, Program 1 2000

Play Audio Below:

We don’t really know the mechanism of resistance to the aromatase inhibitors, but we do know that one of the proposed mechanisms of resistance of tamoxifen is that the selective estrogen-receptor modulator can become an agonist rather than an antagonist. And when that occurs varies in patients, but it is an occurrence. And there are two issues there. 1) It means that when you are on the drug, coming off the drug - going on other hormone therapy may work and 2) resistance may be part and parcel of the mechanism of action as well. And so I’m not too surprised by this. Although, what surprises me, is that you would see this difference in a metastatic study, where the amount of time the patients where on the drugs is relatively short. I would not be surprise at all if in an adjuvant trial, when the patients are on the drug for a long period of time, that you might see some differences.

Relevant Articles:

Oestrogen and growth factor cross-talk and endocrine insensitivity and acquired resistance in breast cancer [Review]. Nicholson, R. I. and Gee, J. M. W. (Reprint available from: Nicholson RI Univ Wales, Coll Med, Tenovus Canc Res Ctr Cardiff CF14 4XX S Glam Wales). British Journal of Cancer. 82(3):501-513, 2000 Feb. No abstract

Differences in immunoreactivity of estrogen receptor (ER) in tamoxifen-sensitive and -resistant breast carcinomas: preclinical and first clinical investigations.
Naundorf, H.; Jost-Reuhl, B.; Becker, M.; Reuhl, T.; Neumann, C., and Fichtner, I. (Reprint available from: Fichtner I Max Delbruck Ctr Mol Med Robert Rossle Str 10 D-13125 Berlin Germany).. Breast Cancer Research & Treatment. 60(1):81-92, 2000 Mar.

Development and characterization of a tamoxifen resistant breast carcinoma xenograft.
Naundorf, H.; Becker, M.; Lykkesfeldt, A. E.; Elbe, B.; Neumann, C.; Buttner, B., and Fichtner, I. (Reprint available from: Fichtner I Max Delbruck Ctr Mol Med Robert Rossle Str 10 D-13092 Berlin Germany).. British Journal of Cancer. 82(11):1844-1850, 2000 Jun.

Approaches targeted to estrogen receptors for treatment of tamoxifen-resistant breast cancer: A brief overview. Terakawa, N. (Reprint available from: Terakawa N Tottori Univ, Sch Med, Dept Obstet & Gynecol Yonago Tottori 683 Japan).. Oncology. 59(Suppl 1):3-4, 2000. No abstract

Concentrations of tamoxifen and its major metabolites in hormone responsive and resistant breast tumours.
MacCallum, J.; Cummings, J.; Dixon, J. M., and Miller, W. R. (Reprint available from: MacCallum J Napier Univ, Dept Life Sci Merchiston Campus,Colinton Rd Edinburgh EH10 5DT Midlothian Scotland).. British Journal of Cancer. 82(10):1629-1635, 2000 May.

How is tamoxifen's action subverted?
Jordan, V. C. (Reprint available from: Jordan VC Northwestern Univ, Sch Med, Rober H Lurie Comprehens Canc Ctr 303 E Chicago Ave,Olson Pavil 8258 Chicago, IL 60611 USA). Journal of the National Cancer Institute. 92(2):92-94, 2000 Jan 19. No abstract

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