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Flaxseed Enhances Inhibitory Effect of Tamoxifen: ER+ Bca

Flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen receptor positive human breast cancer

Jianmin Chen, Evon Hui, Lilian U. Thompson.

Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.

Previous studies in our laboratory have shown that flaxseed (FS) can inhibit the growth of human breast cancer in animal models and clinical trials, in part due to the antiestrogenic effect of its phytoestrogen called lignans.

However, it is not clear whether FS will enhance or antagonize the effect of tamoxifen (TAM), an antiestrogenic breast cancer drug, taken by pre- or post-menopausal women patients.

Thus, this study determined the effect of FS and TAM, alone and in combination on the growth of human estrogen receptor positive breast cancer cells (MCF-7) in athymic mice in the presence of high or low levels of estrogen (E2) to mimic conditions in pre- or post-menopausal women, respectively.

Ovariectomized Balb/c nu/nu mice were injected with MCF-7 cells into mammary fat pads, implanted with an E2 (1.7 mg, 60 day release) pellet and fed with AIN-93G basal diet (BD).

In Experiment 1, when palpable tumor reached ~40 mm2, the E2 pellet was removed (to simulate low E2 level in postmenopausal women) and the mice were randomized to 5 groups and treated for 6 weeks as follows: Groups 1 (negative control), 3 and 5 were fed the BD, and Groups 2 and 4 the 10% FS diet. Groups 3 and 4 also received an implant of TAM (5 mg, 60 day release) pellet.

Group 5 has the E2 implant replaced (positive control). Experiment 2 was similarly designed except that a new E2 pellet replaced the existing pellet (to simulate high E2 levels in premenopausal women) before randomization to 5 groups. An exception is Group 5 (negative control), which did not have the E2 pellet replaced.

Results showed that, at low E2 level, FS alone regressed the pretreatment tumor size by 74%, similar to the negative control.

TAM alone initially caused tumor regression, but later caused an increase. By week 6, TAM decreased the pretreatment tumor size by only 14%. However, 53% tumor regression was induced when FS was combined with TAM.

This represents 44% lower tumor size than that caused by TAM alone. At high E2 level, FS, TAM, and their combination inhibited the tumor growth by 22, 41, and 50%, respectively, compared with the positive control.

The tumor size in the combined FS and TAM treatment was 36% lower than that in the FS group, and 16% lower than that in the TAM group.

In conclusion, FS inhibits the growth of human estrogen receptor positive breast cancer, and strengthens the inhibitory effect of TAM on the tumor growth. FS complements rather than antagonizes the effect of TAM on human tumor growth.



AACR Abstract Number: 973, 2003

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