http://www.eurekalert.org/pub_releases/2016-09/ibr...

Therapeutic inhibition of RANK pathway reduces breast cancer recurrence

The plum link was fascinating and very confusing. Initial research I did showed it was the boron content of prunes that helped with osteoporosis and many sites indicated breast cancer patients should be wary of food containing too much natural boron. This new link also shows that Insulin growth factor increases with prunes...that's not a good thing for cancer even though it may be great for bones.

What's a gal to do?! In a perfect world, I would rather get the estradiol

Wish I could take ACE inhibitors (tried Lisinopril), but the cough was and is a dealbreaker for me: I'm a singer. So I'm on an ARB (Benicar) instead.

Well this is interesting (probably just to me!) I ran across several mouse studies looking at the use magnolol (a magnolia extract) for cachexia and anti-angiogenesis. Apparently magnolol is effective for both. What is surprising is that it induces IGF-1, while at the same time inhibiting HIF-1alpha/VEGF. Go figure.

Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

"In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM) or gemcitabine (TGM), markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC). The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1) production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis."

https://www.ncbi.nlm.nih.gov/pubmed/26600425

(Chen, 2015)

Magnolol suppresses hypoxia-induced angiogenesis via inhibition of HIF-1α/VEGF signaling pathway in human bladder cancer cells.

"Interestingly, magnolol also acts as a VEGFR2 antagonist, and subsequently attenuates the down-stream AKT/mTOR/p70S6K/4E-BP-1 kinase activation both in hypoxic T24 cells and tumor tissues. As expected, administration of magnolol greatly attenuated tumor growth, angiogenesis and the protein expression of HIF-1α, VEGF, CD31, a marker of endothelial cells, and carbonic anhydrase IX, an endogenous marker for hypoxia, in the T24 xenograft mouse model. Collectively, these findings strongly indicate that the anti-angiogenic activity of magnolol is, at least in part, mediated by suppressing HIF-1α/VEGF-dependent pathways, and suggest that magnolol may be a potential drug for human bladder cancer therapy."

http://www.ncbi.nlm.nih.gov/pubmed/23416116

(Chen, 2013)

My first thought was "let's look at the effect of dried plums on HIF-1alpha," but then I thought, to hell with dried plums, let's see what magnolol can do with breast cancer! (And actually there are a few studies of magnolol effectiveness against breast cancer cells, as well A LOT on another magnolia extract, honokiol.) But I digress, lol....

Hah! Wallycat, maybe we should just genetically modify humans with mouse genes, since those dang mice are so easy to cure of cancer! And I know how you feel about cheese...my best friend once said to me, "I love you more than cheese---and ice cream!" (Which gives you a general idea of their level of importance in our lives!)

Hi LizM,

I don't really know much about either, but this study seems to indicate denosumab is better:

Denosumab or Zoledronic acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates.

"In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL."

http://www.ncbi.nlm.nih.gov/pubmed/27270237

(Miller, 2016)

LizM - I replied to another post similar topic. I developed osteopenia after 2 years on Femara which "allowed" my oncologist to order Zometa infuses twice yearly. I've had a total of 8-9 Zometa infusions over the years trying to control this bone loss issue. Last year, I asked to switch to Prolia to give it a try and there was an improvement in my spine after 2 injections last year. I hope to get a few more Prolia injections (easier for me over 30 minute Zometa infusion). Also, I noticed much less joint aches afterwards compared to Zometa infusion. I felt it was time for a change to see if a different type of bone drug would improve my osteopenia status. It had no impact on my WBC. OT - I really hate that insurance companies DICTATE that we had to show bone loss before we could have access to these drugs. IMO any patient taking an AI should be allowed to take a bone drug as PREVENTION if they choose. Hello - we get a flu shot to prevent the flu for goodness sakes!!

http://www.breastcancer.org/research-news/prolia-r...

Quoting fallleaves: "IGF-1 IS tricky, because it is good for us in some ways, but definitely not others! I'm wondering if there's some sweet spot for it, not too much, and not too little."

Any opinion what that sweet spot may be? I had my IGF-1 tested last week after over a year on a very strict ketogenic diet, with end goals (besides losing weight) of lowering blood glucose/A1C, insulin and IGF-1. I wanted low IGF-1 but didn't expect it to go as low as it has. 76 ng/mL with a standard deviation (Z Score) of -1.2 for a woman my age. The lab doesn't classify it as abnormal but there have been studies that show low as well as high IGF-1 levels (U-shaped curve) are associated with increased cancer as well as non-cancer mortality. 76 is definitely on the very low end.

As a side note, anyone with high IGF-1 who needs to lower it, it can definitely be done with a ketogenic diet. The trick is to not eat too much protein, especially animal protein. By definition a ketogenic diet is a moderate and not high protein diet, but it's not easy to figure out what moderate means due to conflicting information online. On some of the keto threads on these boards I've seen people suggesting protein levels that are clearly too high, and might even be dangerous in terms of recurrence risk due to elevation of IGF-1, which of course most people don't ever have tested. I settled on 1g of protein per kg of lean body weight, which for me is in the low 50s. I might need a little more to bring my IGF-1 up a little, but I have no idea what the optimum level might be for a 52 year old woman with a history of ER+ breast cancer.

I already had osteopenia before bc and asked my oncologist about starting Prolia for both bones and preventing mets. She refused -- said several women who used Prolia during the Herceptin phase of treatment got "very difficult skin rashes as an SE, so it is not given at my treatment center. My last Herceptin is the beginning of November; I'm going to try to ask again at my control in January (when the H should have washed out of my body). My mom died of complications from hip fracture surgery (she had osteoporosis) so I want to protect my own bones, especially since I'm on an AI.

Fallleaves - I found this chart on Dr. Fuhrman's site (IGF-1's Link to Cancer) that breaks down the averages by age. In the accompanying article he summarizes the research and says anything under 80 may be detrimental. I'm waiting to hear back from my ND with his opinion but I'm probably going to try to get it up into the 80s at least, whether ND agrees or not.