Therapeutic Strategies Using the Aromatase Inhibitor Letrozole and Tamoxifen in a Breast Cancer Model
| Autor: | Nicol Macpherson, Danijela Jelovac, Olga Goloubeva, Brian J. Long, Apinya Thiantanawat, Venkatesh D. Handratta, Joseph Ragaz, Angela Brodie |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Neoplasms Hormone-Dependent medicine.drug_class Ovariectomy Transplantation Heterologous Mice Nude Anastrozole Breast Neoplasms Pharmacology Drug Administration Schedule Mice Breast cancer Estrogen Receptor Modulators Internal medicine Antineoplastic Combined Chemotherapy Protocols Nitriles medicine Animals Humans Enzyme Inhibitors Aromatase skin and connective tissue diseases Mice Inbred BALB C Aromatase inhibitor biology Fulvestrant Aromatase Inhibitors business.industry Letrozole Uterus Organ Size Triazoles Antiestrogen medicine.disease Disease Models Animal Tamoxifen Disease Progression Linear Models biology.protein Female business hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | JNCI Journal of the National Cancer Institute. 96:456-465 |
| ISSN: | 1460-2105 0027-8874 |
| DOI: | 10.1093/jnci/djh076 |
| Popis: | Background: The antiestrogen tamoxifen has potent activity against estrogen receptor–positive breast cancer, but two nonsteroidal aromatase inhibitors, letrozole and anastrozole, show considerable advantages over tamoxifen with respect to patient survival and tolerability. To determine the optimal way to use letrozole and tamoxifen, we studied their effects on a breast tumor xenograft model, MCF-7Ca, that is responsive to both antiestrogens and aromatase inhibitors. Methods: Female ovariectomized BALB/c athymic nude mice carrying xenograft tumors were treated daily subcutaneously with one of the following fi rst-line therapies for varying durations: no drug (control), tamoxifen (100 g/day) alone, letrozole (10 g/ day) alone, both drugs at the same time, or alternating 4-week courses of each drug (beginning with a course of tamoxifen or beginning with a course of letrozole). Tumor volumes and weights were estimated using linear mixedeffects models. The time to tumor doubling was calculated, and tumor weights in the treatment groups were compared, with adjustments for multiple comparisons being made with either Tukey’s or Dunnett’s procedure. Second-line therapies (with tamoxifen, letrozole, or fulvestrant) were initiated when tumors doubled in size under fi rst-line therapies. All statistical tests were two-sided. Results: The times for doubling of tumor volume were as follows: control, 3– 4 weeks; tamoxifen alone, 16 weeks; tamoxifen alternating with letrozole, 17–18 weeks; tamoxifen plus letrozole, 18 weeks; letrozole alternating with tamoxifen, 22 weeks; letrozole alone, 34 weeks. First-line treatment with letrozole was superior to treatment with tamoxifen alone or with the two drugs combined (at week 16, both P |
| Databáze: | OpenAIRE |
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