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AUDIO: Dr. Jill Siegfried - Is Lung Cancer More Fatal In HRT Recipients?

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Todd:
According to a study published in the journal “Lancet,” the “Los Angeles Times” reports women who take hormone replacement therapy are nearly twice as likely to die from lung cancer.

Hi, this is Todd Hartley, and to bring you up to speed on this developing news EmpowHer, the home of women’s health online, is going to connect you right now with Dr. Jill Siegfried, a professor and Chair of the Lung Cancer Research at the University of Pittsburgh’s Department of Pharmacology and Chemical Biology. Hi, Dr. Siegfried.

Dr. Jill Siegfried:
Hello.

Todd:
Dr. Siegfried, the findings, the findings show that women on HRT, otherwise known as hormone replacement therapy, are no more likely to develop lung cancer, but if they do they are more likely to die. Is that accurate?

Dr. Jill Siegfried:
Yes. Statistically there was a much higher mortality from lung cancer in the hormone replacement arm of the study. There was actually an increase also in lung tumors in the HRT arm. It’s just that it didn’t reach a level of statistical significance so that we can be confident that that is real, but there was a definite trend.

Todd:
It’s just fascinating because we here at EmpowHer, we try to provide, you know, all the sides to the argument so women can make the most informed decision pertaining to their own health. And, you know, often we hear what you are talking about the harmful effects of hormone replacement therapy, but then there are also those doctors that share the benefits. How can a woman weigh out the difference between the harmful effects and the benefits?

Dr. Jill Siegfried:
Well, I think when doctors speak of the benefits, they mostly are referring to short-term hormone replacement therapy use to take care of symptoms that make women very, very uncomfortable when they are going through menopause, and many of the harmful effects we have been seeing are when women have had this long-term use.

So, hormone replacement therapy was originally developed to take care of things like hot flashes and other unpleasant symptoms in menopause. And then, a lot of data came out to suggest, for instance, that women have less cardiovascular disease than men and they live longer. So, you know, we came up with the hypothesis that it was the estrogen that might be doing this. So for instance, heart disease in women definitely does start to increase after menopause.

So the idea was, well, let’s just keep those hormones going for as long as possible and this is going to protect women, but unfortunately, you know, we had a very simplistic idea about what hormone replacement therapy was going to do. So I think it definitely still has a role for helping women get through the perimenopausal period, but the idea that we should use these hormones for 3, 5, 7 years to ward off these other diseases, that’s where we are really running into the problems because now we are seeing that breast cancer goes up, lung cancer deaths went up, and actually there was more heart disease in the women that took hormone replacement therapy for long periods of time.

Todd:
Right, okay, so here’s my concern: It sounds like if this information comes out directly from the WHI which, correct me if I am wrong, came out in 2001, why did it take so long for this information to roll out now in 2009?

Dr. Jill Siegfried:
Well, because they had to follow the women for many years to see who was actually going to die from what types of illnesses; that’s called the follow-up period. So, the study was actually stopped early because the number of heart attacks and so on actually turned out, I believe, to be higher in the hormone therapy group. And that was, I believe, was the primary end point, was they were trying to protect against cardiovascular disease, and it turned out cardiovascular disease was either no better or was worse with the hormone therapy.

So they stopped. The women didn’t take the hormones any more, but they were still in the study. They were continued to be followed for their general health. So suppose someone was diagnosed with lung cancer in 2002. Well, we are not going to know until at least 2004 whether or not they are dying from that disease. You see, so I mean, to get statistical significance when you are comparing groups you have to go out for long periods of time so that more and more people are data points in your analysis.

Todd:
It’s just fascinating to me. Okay, so was there any indication on, or do you have any information on why it is that hormone replacement therapy has this type of increased fatality for lung cancer patients? Is it toxicity?

Dr. Jill Siegfried:
Yes. Well, I think one of the reasons that Dr. Henschke recommended that you speak to me for this topic is that for the past 15 years I have been studying the role of the estrogen receptor in lung cancer, and my lab, and now many others, have shown that there is an additional type of estrogen receptor which we are now calling estrogen receptor beta or B, and the type of estrogen receptor that’s most expressed in breast tumors is now being called estrogen receptor alpha or ERA, and it’s this ERB that we are seeing in lung tumors that we think is mediating growth and progression of the tumor through estrogen.

Todd:
Wow, that is fascinating. So in the most layman terms possible, because we try to boil everything down to the lay woman so it’s easy for everyone to understand…

Dr. Jill Siegfried:
Sure.

Todd:
Explain what you are doing with your studying and give us kind of an overview on what you have discovered, more so than that you just share it with me?

Dr. Jill Siegfried:
Well, for a long time there was data out there that suggested that women that never smoked were making up the large majority of the lung cancer patients who were diagnosed. In other words, if you look at how many men who never smoked are diagnosed with lung cancer compared to how many women who never smoked, it’s far, far in favor of the women.

So that said to me that there was some additional risk factor for lung cancer that might be selectively acting in women and I thought the most obvious thing was to look at hormones like estrogen. So, we started to look at estrogen receptors in lung tumors and we were having a very hard time finding any because we were looking for, what’s now called, the estrogen receptor alpha, which was already known and very well studied in breast cancer.

And then, in about 1995, a new form of the estrogen receptor was discovered by a group in Sweden called ERB or ER-Beta, and it’s a different protein made from a different gene, but it has many, many of the same activities as the ER we already knew about. So as soon as we found out about this and started to look for that in lung tumors, we found it expressed very, very often, actually in lung tumors from women and some from men.

So then we started to study whether if we treated lung cells, lung tumor cells in the laboratory with hormones would we increase their growth rate, and we found that we did, and then we studied it in animals. We made lung tumors in animal, in mice and we asked if we gave those mice estrogen pellets that would release estrogen into their bloodstream would the tumors grow faster, and they did.

And now we have been actually studying the idea that the tumor itself can actually make estrogen in its own local environment and act back on the receptor, which has been found in breast cancer as well. So we think that the lung tumors can grow faster and metastasize, get more aggressive, both from circulating estrogens that might come, say, from hormone replacement therapy and from estrogen that these tumors can actually make right in the lungs.

Todd:
Wow! That is just so fascinating. So before you can figure out how to cure the lung cancer you’ve got to figure out what’s creating it.

Dr. Jill Siegfried:
Exactly.

Todd:
And it sounds like you are really on the forefront there.

Dr. Jill Siegfried:
Yes, and we have actually got two clinical trials going on where we are trying to use some of the same anti-estrogen drugs that have been used for breast cancer in women that have lung cancer, and we are in the middle of doing this. I can’t really tell you the results yet because we are not, we have several years to go before we can really tell what’s going on, but I am hopeful that we will be able to show effects of these drugs and that we may be able to take all the things that were learned clinically for breast cancer and start using those drugs for lung cancer.

Todd:
Now I know that there are women that are estrogen…

Dr. Jill Siegfried:
Receptor-positive?

Todd:
Yes, thank you – estrogen receptor-positive, and for other types of cancers, it sounds like it correlates now into lung cancer.

Dr. Jill Siegfried:
That’s right. That’s right.

Todd:
Wow. Okay, so you have got a couple of years yet before your study comes out. How does it feel to be on the forefront of such big information and not be able to talk about it or not be able to know what your information is going to be for a couple of years?

Dr. Jill Siegfried:
Well, it’s exciting and it’s stimulating, and we just always are trying to work as fast as we can, but, you know, we don’t want to make mistakes or tell the public something that’s not true.

Todd:
Right.

Dr. Jill Siegfried:
Because that can set you back faster. Try to fix a mistake or try to correct a wrong information is actually harder than putting the information out there in the first place.

Todd:
It has its own unintended consequences that roll out from it.

Dr. Jill Siegfried:
That’s right. Well, one other point I wanted to make was that this is the second study that’s actually shown this type of association between HRT and the progression of lung cancer. So, it’s very clear to me, and I think that many in the field would agree with me, that women who are suspected of having lung cancer or have already been diagnosed with it should not take these hormones.

Todd:
And what kind of a test could a woman determine to find out if she is sensitive to…

Dr. Jill Siegfried:
Estrogen receptive beta, yes. Well, that’s one of the conundrums because we don’t have a clinical test yet for the ER-Beta, but I can tell you that about 80% of the tumors have been found to have at least some ER-Beta protein. So, I think that we would just make the assumption that anyone potentially could experience a more aggressive behavior of their tumor if they were taking these hormones.

Todd:
Well, she is Dr. Jill Siegfried. She is on the cutting edge of lung cancer research that’s going on here in the United States, and she is a Professor and Chair of the Lung Cancer Research at University of Pittsburgh’s Department of Pharmacology and Chemical Biology. Dr. Siegfried, thank you so much for helping us empower women.

Dr. Jill Siegfried:
You are welcome. I am glad to participate.

We value and respect our HERWriters' experiences, but everyone is different. Many of our writers are speaking from personal experience, and what's worked for them may not work for you. Their articles are not a substitute for medical advice, although we hope you can gain knowledge from their insight.

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