Effect of CGS 16949A plus tamoxifen on induced mammary tumours in rats

Tominaga, Takeshi; Yoshida, Y.; Shimozuma, Kojiro; Hayashi, Kazuo; Kōsaki, Goro

doi:10.1016/0277-5379(90)90087-a

Cited by 12 publications

(3 citation statements)

References 10 publications

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“…On the basis of a report that mammary cancer patients receiving TAM as adjuvant treatment showed a reduced risk of new primary lesions in the contralateral mammary gland, 17) a large-scale trial of chemoprevention by TAM for women at high risk of mammary cancer has been initiated in the United States and Europe. 18) Recent studies in experimental animals have shown that the combination of TAM with an aromatase inhibitor, 19) 9-cis-retinoic acid, 20) the somatostatin analogue octreotide, 21) or dehydroepiandrosterone 22) is useful for chemoprevention of mammary cancer.…”

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confidence: 99%

Chemoprevention of N‐Nitroso‐N‐methylurea‐induced Rat Mammary Cancer by Miso and Tamoxifen, Alone and in Combination

Gotoh

Yamada

Ito

et al. 1998

Japanese Journal of Cancer Research

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We examined the effects of a Japanese fermented soybean product, miso, and tamoxifen (TAM), alone and in combination, on N-nitroso-N-methylurea (MNU)-induced rat mammary cancer. Seven-week-old female CD/Crj rats received a single i.v. dose (50 mg/kg body weight) of MNU. After administration of MNU, the rats were divided into 4 groups: regular diet (control), 10% miso diet, regular diet+ + + +TAM, and 10% miso diet+ + + +TAM. TAM was implanted s.c. in the form of pellets containing 2.5 mg at the same time as MNU was administered. All rats were observed for 18 weeks after MNU administration. Incidence (percentage of rats with tumors) and multiplicity (mean tumors/rat) of mammary tumors were 91% and 4.5 in the control, 77% and 2.4 (P< < < <0.05) in the 10% miso group, 68% and 1.4 (P< < < <0.01) in the TAM group, and 10% (P< < < <0.0001 or less) and 0.2 (P< < < <0.0001) in the 10% miso+ + + +TAM group. In the second experiment, the effect of the combination of miso and TAM on established rat mammary tumors was investigated. When the mammary tumors induced by MNU reached 10 to 25 mm, the rats were divided into 3 treatment groups: regular diet, regular diet+ + + +TAM, and 10% miso diet+ + + +TAM. At 6 weeks after the start of treatment, the mean tumor size in the control and TAM groups was 160% and 141% of the pretreatment value, but a decrease to 85% of the pretreatment value was produced by the combination of miso and TAM, and this was significantly different from both the control and TAM groups (P< < < <0.01 and P< < < <0.05, respectively). These results indicate that miso is useful in protecting against mammary cancer and it can be expected to have a potent antitumor effect, especially when used in combination with TAM.

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confidence: 99%

Chemoprevention of N‐Nitroso‐N‐methylurea‐induced Rat Mammary Cancer by Miso and Tamoxifen, Alone and in Combination

Gotoh

Yamada

Ito

et al. 1998

Japanese Journal of Cancer Research

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“…Preclinical data regarding the combinations of an antiestrogen with an aromatase inhibitor are conflicting. Fadrozole with tamoxifen demonstrated better antitumor effects than either single agent when tested in an animal model [3]. Conversely, formestane plus tamoxifen has been shown to be less effective than formestane alone [4].…”

Section: Aromatase Inhibitors With Antiestrogensmentioning

confidence: 98%

Combination Endocrine Therapy in the Management of Breast Cancer

2001

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Combination endocrine therapy has long been sought after as a means to better treat breast cancer. Agents that suppress estrogen production are given with agents that suppress estrogenic activity at the cellular level. Historically, these combinations have resulted in initial improvements in response rates, but relapse-free and overall survival were not significantly improved. Also, the increased toxicity seen with these regimens was limiting. New endocrine therapies with more potent activity and less toxicity have led to a resurgence of this idea in the management of breast cancer. Complete estrogen blockade has been compared with single-agent treatments in many different settings. The endocrine effects of this type of therapy are intriguing, but apparently do not readily predict a clinical advantage. The combination of an aromatase inhibitor and an antiestrogen, despite pharmacokinetic interactions, may prove to be beneficial. Results from ongoing trials are eagerly awaited to further address this question in postmenopausal breast cancer patients. For premenopausal breast cancer patients the options are more complex. Clinical outcomes with leutinizing hormone releasing hormone (LHRH) agonists plus aromatase inhibitors are limited to very small phase II studies and are not clearly superior to single-agent therapy. Clinical data in the metastatic setting with premenopausal patients favor the use of an LHRH agonist with tamoxifen over the use of an LHRH agonist alone. However, a similar comparison with tamoxifen alone is lacking with only one trial including this as a treatment arm. Adjuvant therapy with this combined endocrine approach (LHRH agonist plus antiestrogen) has been more extensively studied, but lacks crucial comparisons necessary for making complex treatment decisions. Hopefully, through investigative diligence and ingenuity this issue can be adequately understood. However, many exciting new agents are on the horizon that offer hope to further advance the progress made to date although further confounding the questions already answered.

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“…The main assessments are time to breast cancer recurrence, overall survival and tolerability. It will be interesting to see whether the superiority of the aromatase inhibitor-tamoxifen combination over tamoxifen alone in the rat tumour model translates into the clinical setting (Zaccheo et al, 1993;Tominaga et al, 1990).…”

Section: Adverse Eventsmentioning

confidence: 99%

Aromatase inhibitors and their future role in post-menopausal women with early breast cancer

Lønning

1998

Br J Cancer

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Summary Anastrozole is the first aromatase inhibitor to show a significant survival advantage over megestrol acetate in post-menopausal women with advanced breast cancer. The rationale for extending the use of aromatase inhibitors to the treatment of early breast cancer is based on the efficacy observed in the advanced setting, combined with good tolerability and a convenient dosing regimen. Furthermore, oestrogen deprivation by ovarian ablation (similar to oestrogen antagonism with tamoxifen) is already established as an effective adjuvant treatment in premenopausal women with modality breast cancer. Anastrozole produces a profound suppression of plasma oestrogen levels which is greater than that obtained with earlier aromatase inhibitors (formestane, aminoglutethimide) or megestrol acetate. This could account for the differences in clinical efficacy seen between anastrozole and megestrol acetate. In terms of benefits over other endocrine agents, anastrozole causes significantly less weight gain than megestrol acetate; it does not have the partial agonist activity of tamoxifen, and is unlikely to lead to tumour stimulation in patients resistant to tamoxifen or to exert proliferative effects on the endometrium. The lack of oestrogen agonist activity, however, may possibly have detrimental effects on bone mineral density and blood lipid profile. Current clinical trials are investigating the efficacy and safety of anastrozole in the early breast cancer setting. The results of these trials will help to determine whether anastrozole has any benefits over tamoxifen, the current treatment of choice in post-menopausal women with early breast cancer.

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Effect of CGS 16949A plus tamoxifen on induced mammary tumours in rats

Cited by 12 publications

References 10 publications

Chemoprevention of N‐Nitroso‐N‐methylurea‐induced Rat Mammary Cancer by Miso and Tamoxifen, Alone and in Combination

Chemoprevention of N‐Nitroso‐N‐methylurea‐induced Rat Mammary Cancer by Miso and Tamoxifen, Alone and in Combination

Combination Endocrine Therapy in the Management of Breast Cancer

Aromatase inhibitors and their future role in post-menopausal women with early breast cancer

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