Wende M. Kozlow, MD - University of Virginia Postdoctoral-Multidisciplinary Award:

My research is exploring what happens to bone while on aromatase inhibitors. Tomoxifin has been bone spearing. It has a positive effect on the bone. However, the aromatase inhibitors in the clinical trials we have seen that the patients are losing bone. The aromatase inhibitors suppress postmenopausal estrogen levels to an even lower level. And, this has resulted in increased bone turnover in osteoporosis.

And, we are hypothesizing that increased bone turnover will release growth factors that are housed in bone into the micro environment and actually may predispose to breast cancer metastasis making bone a favorable environment for breast cancer cells to go and to settle and then grow.

We use nude mice that can't actually mount an immune response toward breast cancer cells and, we gave these mice aromatase inhibitors. We also had a vehicle to use as control and then we also gave some of the mice the bisphosphonates (?) zoledronic acid or Zometa to see if this would counteract the effect of high bone turnover due to the aromatase inhibitor.

And, we can see that the mice that are given Letrozole alone will have a reduced bone density. But, if you use Letrozole plus Zometa which is the bisphosphonates, you can actually restore the loss of bone density and you can completely inhibit the high bone turnover due to oxygen deficiency from the aromatase inhibitor. So, we are actually able to see that looking at total body bone density, bone density at the spine, the tibia, and the femur.

Over here we look at the colony-forming unit assays to look at what Letrozole, which is the aromatase inhibitor, does in the bone micro environment. And, we can see that they are increased fibroblast, osteoblast which make new bone, and osteoclast which re-absorb (?) bone in the mice that were treated with Letrozole versus control. So, this is showing that there is definitely increased bone turnover at the cellular level. As the cells that are responsible for bone turnover are increased when you give the mice aromatase inhibitors. I think what we need to do is to demonstrate that not only is there high bone turnover with aromatase inhibitor therapy, but also that mice then who are then given the human breast cancer cell line will then have increased bone metastases and reduced survival compared to mice who are not given aromatase inhibitors. And, not only that, but show that we can block the increased bone metastases from aromatase inhibitor therapy if we also give bisphosphonates at the same time. And, that part of the experiment is still ongoing.

I think that the Breast Cancer Research Program is a great funding source for researchers such as myself. It allows us another opportunity to find funds for our research. I think it's also great the breast cancer consumers actually have a say in who gets funded. And, I think it gives breast cancer survivors some control. I think when you are diagnosed with breast cancer just like with other cancers and diseases, you lose some control over your life. I think this allows them to exert some control back and have a say in where the research is going.