new cause of resistance to herceptin IDd-- hold off on those ice cream sundaes!!!!

[Lani]

Breast Cancer Res. 2015 Apr 24;17(1):57. [Epub ahead of print]
Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity.
Duong MN1, Cleret A2, Matera EL3, Chettab K4, Mathé D5, Valsesia-Wittmann S6, Clémenceau B7,8, Dumontet C9,10.


Abstract Introduction
Trastuzumab has been used in the treatment of human epidermal growth factor receptor 2 (HER2)-expressing breast cancer but its efficacy is limited due to de novo or acquired resistance. Although many mechanisms have been proposed to explain the resistance to trastuzumab, little is known concerning the role of the tumor microenvironment. Given the importance of antibody-dependent cell-mediated cytotoxicity (ADCC) in the antitumor effect of trastuzumab and the abundance of adipose tissue in breast, we investigated the impact of adipocytes on ADCC.
Methods
We set up a co-culture system to study the effect of adipocytes on ADCC in vitro. The results were validated in vivo in xenograft mice.
Results
We found that adipocytes, as well as preadipocytes, inhibited trastuzumab-mediated ADCC in HER2-expressing breast cancer cells via the secretion of soluble factors. The inhibition of ADCC was not due to a titration or a degradation of the antibody. We found that adipose cells decreased the secretion of interferon-gamma by natural killer cells, but did not alter their cytotoxicity. Pre-incubation of breast cancer cells with the conditioned medium derived from adipocytes reduced the sensitivity of cancer cells to ADCC. Using a transcriptomic approach, we found that cancer cells undergo major modifications when exposed to adipocyte- conditioned medium. Importantly, breast tumor grafted next to lipoma displayed resistance to trastuzumab in xenograft mouse models.
Conclusions
Collectively, our findings underline the importance of adipose tissue in the resistance to trastuzumab, and suggest that approaches targeting the adipocyte-cancer cell crosstalk may help sensitize cancer cells to trastuzumab-based therapy.

[LaDonna28]

My brain can't wrap around what this means. Can someone tell me in laymen terms?? Thanks!

[Nguyen]

Anyone feels free to jump in if I am not correct.

Essentially researchers discover (via test tube and mouse model) that another possible cause of Herceptin might be fatty cells, particularly if breast cancer cells grow next to fatty cells. The abstract implies two Herceptin resistance mechanisms for tumor cells growing next to fatty cells. These tumor cells undergo some sort of changes, and the fatty cells cause the immune system killer cells to reduce the number of bullets it can fire at the cancer cells. So the researchers suggest develop treatment that block communication between fatty and tumor cells.

So the message is to reduce fat intake (hence hold off those sundaes). Strangely enough obesity is a cancer risk factor for post menopause women, but slightly decreases bc risk for pre menopause women. Post menopause women have less hormone so it's another clue.

Nguyen

[Pamelamary]

Sounds as if I must watch my weight if I want Herceptin to keep on working - and I do!
Thanks Lani.

[LizzElliot]

Ladies, I am really struggling here. It seems post treatment, with the chemo-induced post-menopause, or the tamoxifen introduction (which I have now switched to Femara) -- altho' I have researched and am only eating the best of veggies and antioxidant foods... And altho' I am working out like I never have in my life, the weight just flew on starting in January, growing through March, and I'll say April with the switch to Femara, it has slowed some (or is it that in March April I started working out like crazy?). But if to keep cancer from returning we must be slim, I'm having a hard time getting back to slim or slender.
Two hours a day in the gym is possible while I'm still off work, but I cannot imagine what I'll do after I go back to work. I keep working out in hopes I don't have to buy new clothes to interview in. I am up at least two dress sizes.
I love that I am NED, but being scared of a return, this weight thing has me stymied in what to do.
Lizz.

[StephN]

It seems that the fatty tissue may be the culprit, so cutting the fat intake in conjunction with firming up should help.

Not sure actual "weight" is the factor - mainly the composition of a person's body weight.

Keep moving Lizz, as this is good overall in our rehab from the ills of chemo.

[LaDonna28]

Interesting that that are saying it is the fat is the culprit given the fact that women with dense breasts are more prone to getting cancer; however, women with dense breasts have less fat and more connective tissue in their breasts... Doesn't make sense, but then nothing about cancer really does!

[Mtngrl]

I'm reluctant to jump from what this study says to concluding that eating fat can make you Herceptin resistant. Fat in food gets metabolized--i.e. used for running our bodies, including several processes/tissues that require fatty acids. Excess calories get stored as adipose tissue, regardless of the source of the excess calories. So the sugar in those sundaes is just as likely to form adipose tissue as the fat.

I've seen a lot of references to "tumor microenvironment" lately. That does argue for a holistic approach to health, including controlling stress and anxiety, boosting the immune system, exercising, and eating foods that are high in antioxidant and anti-inflammatory compounds. Besides, those foods and spices are delicious.

[LaDonna28]

I have come to the conclusion that I can only do so much. I also have given up so many vices, that the idea of giving up everything I like would make me miserable and stressed. I hereby give it all to God. When it is my time He will take me. In the meantime, I will pray for good health and I will enjoy my ice cream!��