beware of soy if on Faslodex

[Lani]

1: Endocr Relat Cancer. 2007 Jun;14(2):317-24.
Effects of a phytoestrogen-containing soy extract on the growth-inhibitory activity of ICI 182 780 (faslodex/fulvestrant) in an experimental model of estrogen-dependent breast cancer.

Gallo D, Mantuano E, Fabrizi M, Ferlini C, Mozzetti S, De Stefano I, Scambia G.
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
The study reported here was designed to determine whether a phytoestrogen-containing soy extract (SSE) could negate/overwhelm the inhibitory effects of ICI 182 780 on the growth of estrogen-sustained human breast cancer xenografts (MCF-7), in ovariectomized athymic mice. As expected, estradiol-supplemented tumors did not grow over the study period in ICI 182 780-treated females; concomitant administration of 50 mg/kg per day SSE slightly potentiated the inhibitory activity of the drug, while at 100 mg/kg per day, SSE partially negated ICI 182 780 activity. In keeping with these in vivo outcomes, we observed that the level of cyclin D1 (and progesterone receptor) in MCF-7 xenografts was considerably reduced by ICI 182 780, an effect enhanced by concomitant treatment with 50 SSE, but reduced by the higher dosage (i.e. 100 mg/kg per day). Thrombospondin-1 (TSP-1) and kallikrein 6 (KLK6) levels were also reduced following ICI 182 780, although to a lesser degree; again, combined anti-estrogen and SSE produced a dose-dependent regulation in TSP-1 and KLK6 tumor level, with a further reduction in the mRNA gene expression at 50 SSE (compared with ICI 182 780) and a partial reversion of the drug-induced down-regulation at 100 mg/kg per day. No modulation was detected in the serum concentration of IGF-1 (a potent mitogen for estrogen receptor-positive breast cancer cell lines) either upon treatment with ICI 182 780 or concomitant administration of the anti-estrogen with SSE. In conclusion, results from this study raise concerns about the consumption of isoflavone supplements in conjunction with ICI 182 780 therapy, in postmenopausal women with estrogen-dependent breast cancer.
PMID: 17639047 [PubMed - in process]

[suzan w]

what about consuming foods with soy...ie: soy milk, tofu etc??

[Susan]

What does that study mean in plain ol' English? I don't get it!
Sue

[hutchibk]

Sounds to me like direct sources of soy, i.e. soy beans/edamame, soy milk and tofu should probably be avoided if on Faslodex, as relatively large amounts of isoflavones are present in whole soybeans, roasted soy nuts, tofu, tempeh, soy milk meat subsitutes, soy flour, and some soy protein isolates. In addition, the isoflavones present in soy are available as supplements, in capsules or tablets.

It sounds like it interferes with the estrogen binding action of the Faslodex.

[Hopeful]

Lani,

"As expected, estradiol-supplemented tumors did not grow over the study period in ICI 182 780-treated females; concomitant administration of 50 mg/kg per day SSE slightly potentiated the inhibitory activity of the drug, while at 100 mg/kg per day, SSE partially negated ICI 182 780 activity."

Do I read this correctly:

1. The tumors did not grow during the study
2. 50 mg/kg per day enhanced the drug
3. 100 mg/kg per day diminished the effect of the drug

If so, why would different amounts of the soy have opposite effects in the same individual?

Hopeful

[Lani]

that different amounts of the same compound cause differing (even opposite effects) It may be that some feedback mechanism only comes into place when a threshold has been exceeded and that feedback mechanism changes which pathway is dominant.l

Thinks of a line at the airport with a person feeding people into different lines. Once the lines get too long, people may be ciphoned off to automated machines, other checkin desks, or told to go with another airline.

The body has to prioritize and have ways for different amounts of substances to be processed as well.

The reason the estradiol had no effect initially is that faslodex had caused the ERs to degrade and there was no receptor to work on. But Estrogen also has effects on the membrane and cytoplasm besides effects on the nucleus (and probably lots of other effects even less well described or not yet discovered!)

The important point was that a certain concentration (and we do not yet know what that is in humans) soy isoflavones could decrease/possibly negate the effects of Faslodex, so caution might be prudent until this is better understood

Hope this helps!

[hutchibk]

H - from the reading I have done over the last few years, the amount of soy (and the source) being ingested is the most complicated and controversial piece to the soy puzzle. There seems to be lots of info on the pro side for soy, but it's not as simple as just adding soy to the diet. From what I have read, research is still out on ingesting it, but ingesting too little can be detrimental/not protective and possibly be an estrogen fuel, and ingesting too much can be detrimental, possibly be an estrogen fuel and now seems to interfere with certain meds.

All of this confusion is why my onc asked my 3 years ago to stay away from soy while on the b/c path. He said it is just too controversial and he would rather us be safe than sorry. I loved my tofu, edamame and soy milk so much, but I gave it up at his request...

No worries now. I missed it at first, but I don't anymore. I have taken a liking to rice milk and wheat protein when I want some of my favorite veggie recipes. I do have the occasional tofu dish, but only once every few months.

[Hopeful]

Lani,

Many thanks for your explanation - it is even more helpful than the article itself.

Hopeful