Rhonda: I was reading - I think it may be the American Cancer Association - had published some statistics on how obesity can increase the risk of breast cancer by two-fold. And also, specifically looking at some of the mechanisms by which obesity can increase breast cancer risk. There were a variety of them, including increased inflammation, increased hormone - so estrogen, and also increased fasting insulin levels.

Ruth: Yes. I think we've known for a long time about sex hormones, in particular, estrogen a risk factor. Because some of our first, really successful drugs, were based on blocking the action of estrogen. Estrogen is a growth factor, so it appears if we can block that it can reduce your risk or reduce your risk of recurrence. And we have some pretty effective drugs that have made a big difference. It's more recently that we've realized that other growth factors have the same type of impact, and it makes... it's almost common sense. If estrogen is a growth factor, and that increases growth rates of tumors, well, what about insulin? It's also a growth factor it encourages metabolism. So we do believe that perhaps high levels of circulating insulin may be really central to the whole process of developing breast cancer and promoting its growth. And high levels of insulin are definitely found in women who are overweight, if you're less physically active, and then of course among diabetics often have high circulating levels of insulin. So we do...are becoming more aware that sort of that may be kind of a common road where many different syndromes lead to the risk...increased risk of breast cancer.

Rhonda: And so you mentioned that people that are overweight and people that are obese have higher circulating insulin levels. They also have higher circulating estrogen levels, right? So fat can secrete...? Is it...am I right, fat can secrete estrogen, or is that something that...

Ruth: Fat can...yes. So that's pretty central. And then, what we also know is that people who have high levels of insulin have lower levels of serum-hormone binding globulin, something called SHBG which binds estrogen. So it can prevent it from being active. So they seem to be related, they're not just two independent pathways, they actually play off each other.

Rhonda: Interesting. And you say...you brought up something that was very I think important, and that is you said that these growth factors, they promote the growth of tumor cells, of cancer cells.

Ruth: Right. That's in a very general way.

Rhonda: Right.

Ruth: Right.

Rhonda: Yeah, so you're... Something, you know, something's causing the initial damage, the cells become damaged and, you know, we have a lot of mechanisms inherent in our cells that can sense damage and say well, okay, I'm going to die, I'm going to kill myself because if I don't, may potentially lead to, you know, a cancer cell.

Ruth: Right.

Rhonda: But if you have all these growth signaling factors happening in the presence of that damage, it's sort of saying, "Hey, no, no keep going, keep growing, don't die. Grow, grow, grow.

Ruth: Yes.

Rhonda: And, you know, so that's sort of like I think the combination between things that are causing the damage which possibly high inflammation, so obesity also is associated with high inflammation and then, you know, the combination of the inflammation and the high insulin, the high insulin like growth factor, the high estrogen it's sort of like this detrimental combination of damage and growth signals to allow them to survive.