Lung Cancer in Women

Doctors once considered lung cancer a disease of older men, but today lung cancer is the leading cause of cancer death among U.S. women. Now that researchers are taking a closer look, it's becoming clear that lung cancer is a different disease in women than it is in men.

Early research indicates that susceptibility to tobacco smoke, estrogen and even differences in DNA may all play a role in the way lung cancer behaves in women. Understanding what makes lung cancer in women unique should help researchers develop targeted therapies for women. Below, Jyoti Patel, MD, an instructor of medicine at the division of hematology-oncology at Northwestern University in Chicago, discusses what we know so far about lung cancer in women.

Are women's smoking rates declining around the world?
In the United States, women's smoking rates peaked in the 1960s and have been falling since then. While smoking in men has declined by half since the 1960s, smoking in women had only decreased by 25 percent. About 20 to 25 percent of U.S. women continue to smoke.

Worldwide, as women are given political and social freedoms, they pick up smoking. We are now seeing this play out in Asia and Africa. So, if you look at Japan, for example, this is a country with a culture in which women did not smoke for years. There is a study that actually showed that the smoking rate in women doubled over 10 years, from 9 to 18 percent, when tobacco advertising increased in the late 1980s to early 1990s.

Do women have different smoking habits than men?
Observational studies have shown that women tend to use smoking as an outlet or as stress relief, so they'll have a quick cigarette. They probably smoke differently than men do, because it is a quick cigarette. They inhale more deeply and more quickly, so they may be prone to a different carcinogen exposure than men, because if you smoke really deeply, you affect some of your more distal airways, which are farther from the major airways. Men may have a slower, more lingering approach.

How have the trends in lung cancer deaths changed?
For many years, most of us felt that lung cancer was a disease of smoking men in their '60s and '70s. But starting in the 1980s, a vast number of women were diagnosed with lung cancer. If you really look back, so there's been a 600 percent increase in death rates from lung cancer in women since 1930.

In 1987, the lung cancer death rates in women exceeded breast cancer death rates and have been climbing since then. Most recently, we've found that more women die from lung cancer than from breast and ovarian cancer combined.

Are women who have never smoked more likely to develop lung cancer than men who've never smoked?
Absolutely. We don't have good numbers from the United States, however, when you look at Asian countries, we find that women who've never smoked and are diagnosed with lung cancer represent about 90 percent of lung cancer never-smokers. So women outnumber men in this category almost 9 to 1.

Does lung cancer affect women who are former smokers?
Lung cancer now affects former smokers and smokers equally. I would say about 50 percent of all of my patients stopped smoking years ago and about 50 percent of my patients are women. The prototypical patient I see now is a woman who smoked, probably in college, and stopped in her 30s, when she had small children, and has been living healthily for 25 years and now has lung cancer.

Your risk decreases when you quit smoking, but it never returns to normal. Once people have been exposed to the toxins, you can't take that away. Certainly, if you are a smoker, the best thing you can do is quit. But, overall, the message, I think, to a teenager, is never start.

Are women more susceptible to the carcinogenic effects of tobacco smoke?
There has been a lot of media coverage about whether women are more susceptible to lung cancer than are men. When you look at the studies, I think that they probably have the same susceptibility. But I think that lung cancer is different in women.

For example, historically, most lung cancers were squamous cell carcinomas, which are cancers that were located more centrally, so in cells that line the major airways. But if you look at all lung cancers, women are more prone to get adenocarcinoma than are men. Adenocarcinoma is a cancer that we usually find in the more distal airways that comes from gland-forming cells. So you can have an adenocarcinoma of the colon, of the breast, almost any part of your body. Adenocarcinoma was a rare cancer at the turn of the century, but it's become much more common.

Does estrogen play a role in lung cancer?
Yes, estrogen may play a role in lung cancer progression. We've found that estrogen receptors are present on lung cancer cells and lung cancers that we've cut from tumors. It appears that estrogen may promote cancer growth by working in concert with EGFR (epidermal growth factor receptor), a gene involved in cancer development. And that plays an important role in some lung cancers.

Estrogen could also affect the enzymes which process the toxins from cigarette smoke differently, so there may be more DNA damage to cells in women than men. Women also have less DNA repair activity going on in their cells and more molecular aberrations.

On the other hand, women with lung cancer always live longer. So estrogen actually may play a role in survival, but we don't yet understand its protective effect.

Do you think women with lung cancer should be studied separately?
We've found that, with these newer chemotherapy drugs, women tend to respond differently, and I think we need to address some of these differences in response. And with the advent of targeted drugs such as the drug Iressa, we have seen that women actually have a higher response rate than do men. Studies of Iressa are planned in select groups of patients, such as women and never smokers.

Also, we now have more ways of interfering with certain hormones in our body and need to explore whether these drugs could prevent lung cancers in patients who have smoked in the past. Drugs such as the anti-estrogen drug tamoxifen, used for breast cancer, would be important to look at. There is a study that is ongoing at the University of Pittsburgh and the University of Wisconsin in which patients with lung cancer that has been resistant to treatment are being treated with Iressa and an anti-estrogen drug called Faslodex. More studies like this one will be important to conduct, as we understand more about estrogen's role in lung cancer.

We also need to make efforts in screening, such as the use of CT scans in smokers or former smokers, and prevention that directly target women. The problem is that earlier prevention and screening trials were performed mainly in men and so we're not sure if what we found true in men in the 1970s is applicable to women in the 21st century.

What is your advice to women regarding lung cancer?
I think the most important thing is that, if you smoke, you need to quit. If you've never smoked, you should never start. After that, women need to be aware of the symptoms and realize that they can be at risk. So if they have a cough or a nagging chest pain or wheezing, they need to seek medical attention and know that we do have better therapies than we used to, so if they are diagnosed, we hope that we'll be able to help them live longer.

And so do you think women underestimate their lung cancer risk?
Absolutely. I think lung cancer is not even on the radar for most of my women patients who have lived healthy lives, get mammography, go for Pap smears. But women who have a substantial smoking history could be at higher risk for lung cancer than for any of those other cancers.

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