EFFECT OF OMEGA-3-FATTY-ACIDS ON THE PROGRESSION OF METASTASES AFTER THE SURGICAL EXCISION OF HUMAN BREAST-CANCER CELL SOLID TUMORS GROWINGIN NUDE-MICE

We showed previously that a diet rich in linoleic acid (LA), an omega- 6 fatty acid, stimulates the growth and metastasis of human breast can cer cells in athymic nude mice, In contrast, diets supplemented with e icosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), omega-3 fatt y acids, exert suppressive effects, We have now assessed EPA and DHA a s adjuvant nutritional therapy in the nude mouse model and compared th e responses when the intervention was commenced 1 week before (''neoad juvant'') or immediately after (''postoperative adjuvant'') surgical e xcision of the primary tumor, Female nude mice received a high-fat, 8% LA diet beginning 7 days before 10(6) MDA-MB-435 human breast cancer cells were injected into a thoracic mammary fat pad, As the tumor surf ace areas approached 0.7 cm(2), the mice were assigned to either conti nue on the LA-rich diet or to commence one containing 8, 4, or 2% EPA or DHA, Seven days later, the mammary fat pad tumors were excised; the mice still consuming the 8% LA diet were then allocated sequentially to either continue this diet or commence one of the six postexcision o mega-3 fatty acid dietary interventions, Eight weeks later, the mice w ere necropsied and evaluated for local recurrence and lung metastases, Although there were no differences in the incidence of local recurren ce between groups, EPA and DHA both inhibited the development of lung metastases, When the dietary interventions were commenced 7 days befor e surgery, the severity of lung metastasis was reduced by the two omeg a-3 fatty acids in a dose-dependent manner; at all three levels, the s uppressive effects were statistically significant (P < 0.05). Postexci sion EPA treatment produced small, statistically insignificant effects , but lung involvement was reduced significantly by feeding DHA at the 2 and 4% levels (P < 0.05), Overall, these results suggest that omega -3 fatty acids may have a place as adjuvant nutritional therapy in bre ast cancer and particularly as part of a neoadjuvant regimen.