Lung cancer in women

Is lung cancer different in women? Yes and no. Lung cancer causes tremendous suffering and kills 165,000 people every year — more than any other single cancer. It takes a greater toll on women than breast cancer, ovarian cancer, and uterine cancer combined.

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By  Harvard Medical School Published  December 12, 2005

|~||~||~|Lung cancer causes tremendous suffering and kills 165,000 people every year — more than any other single cancer. It takes a greater toll on women than breast cancer, ovarian cancer, and uterine cancer combined. Lung cancer hasn’t inspired much activism or advocacy because it’s often viewed as a condition that smokers bring on themselves. But no one is immune.

Women and men share the same risk factors, the greatest of which is exposure to tobacco smoke. But among nonsmokers, more women than men develop the disease. Researchers have also found that women, especially nonsmokers, tend to respond better to certain therapies.

Women and men tend to get different forms of the disease; understanding these differences should improve diagnosis and treatment in both sexes.

A women’s health issue

Lung cancer has increasingly become a special concern for women. Women have never smoked in the same numbers as men, at least in the U.S., yet they account for nearly half the new cases. And although lung cancer deaths have dropped steadily in men since 1990, they have continued to rise in women, leveling off a bit only recently. These disparities exist mainly because women continued to smoke in the 1960s and 1970s, when men were starting to quit.

The rate of lung cancer deaths in men began falling in 1990 but continued to rise in women until very recently, in large part because women started smoking later than men did. Smoking began to decline after the publication of the first Surgeon General’s Report on Smoking and Health, in 1964. However, women have given up the habit more slowly than men have.

What worries many experts is that smoking increased in women even after its dangers became known. One reason is that women believe that smoking helps them control their weight. Another reason is that women have a harder time quitting than men do. Some experts think the death rate in women may start climbing again once growing numbers are well into their 60s, when most diagnoses are made. Another concern is that tobacco use continues to rise among teenage girls.

Lung cancer in women
Risk factors for both women and men include family history, prior lung disease (such as tuberculosis or chronic obstructive pulmonary disease), and exposure to asbestos, secondhand smoke, radon (a naturally occurring gas), and certain other airborne substances. Diet may also be important; for example, lung cancer is associated with a low intake of fruits, vegetables, and grains and a high consumption of fat and cholesterol. But smoking, of course, is by far the biggest culprit, causing 85%–90% of the disease.

Lung cancer symptoms
l A cough that persists and worsens over time l Persistent chest pain
l Coughing up blood
l Shortness of breath, wheezing, or hoarseness
l Difficulty swallowing
l Recurring pneumonia or bronchitis
l Swelling of the neck or face
l Loss of appetite
l Weight loss
l Fatigue

Several studies suggest that, compared with men, women who smoke develop lung cancer earlier and with less smoke exposure. But whether women are actually more susceptible to smoking’s effects is not really known. Study results are conflicting and inconclusive.

One problem is that it’s difficult to take into account the effects of secondhand smoke and other circumstances, such as how deeply a person inhales or how much of a cigarette she actually smokes. Research does suggest that lung cancer is not biologically identical in women and men. The most common type of lung cancer in women is adenocarcinoma. In men, it is squamous cell carcinoma, which produces more symptoms and thus is easier to detect.

More than two-thirds of nonsmokers with lung cancer are women, and most of them have adenocarcinoma. Women smokers are also more likely than men who smoke to develop small cell lung cancer, a form that spreads fast and has the poorest prognosis (see table, “Lung cancer types and characteristics”).

Lung cancer types and characteristics

Small cell lung cancer (15%–20% of all lung cancers): The most aggressive form of lung cancer; often spreads before symptoms appear. Almost always caused by smoking. Chemotherapy may help prolong survival.

Non-small cell lung cancer (80%–85% of all lung cancers):

Adenocarcinoma: The most common type of lung cancer in women and nonsmokers. Usually found in the outer edge of the lung. Spreads early on to other parts of the body.
Squamous cell carcinoma: The most common type of lung cancer in men and smokers. Usually develops in the mucous lining of the bronchi. Detected earlier than other types of lung cancer.

Large-cell carcinoma: Least common non-small cell lung cancer. Tumors spread quickly.

Genes and hormones
Some of the differences in the development of the disease may be explained by genetic and hormonal factors, possibly in combination. Women are more likely than men to have certain genetic mutations associated with lung cancer risk. Some may be inherited; others may result from exposure — active or passive — to tobacco smoke.

For example, in one study comparing smokers who had lung cancer surgery, women were three times more likely than men to carry a mutation known as K-ras, which appears to make tumors more aggressive. The investigators think that K-ras may spur cancer growth in response to hormones, especially estrogen.

Women who smoke show more DNA damage and less capacity to repair it than men do. Several genes are thought to be involved. One called GRPR (gastric-releasing peptide receptor) is linked to abnormal growth of lung cells and is much more active in women, both nonsmokers and smokers, than it is in men. Estrogen may fuel cancer cell growth or interact with genes that boost the effects of carcinogens.

Early menopause, which causes a drop in estrogen levels, has been linked in very preliminary studies to a lower risk for lung cancer; postmenopausal estrogen therapy may increase the risk. Much more study is needed, but if estrogen proves to be a risk factor, then medications that reduce estrogen levels, such as tamoxifen, could be useful in prevention and treatment.

Another factor that may have special significance for women is epidermal growth factor receptor (EGFR), a protein found in abundance on the surface of lung cancers. Researchers have found that lung cancer patients with mutations in EGFR tend to respond better to Iressa, one of the newer, targeted cancer therapies. These mutations are more common in nonsmokers and in women. In September 2005, the U.S. Food and Drug Administration approved a test for detecting EGFR mutations in people with non-small cell lung cancer. Use of the test may help identify patients who are likely to benefit from these drugs.

How concerned should patients be if they don’t smoke? Certainly you should evaluate them if they have symptoms such as new shortness of breath or a persistent cough (see “Lung cancer symptoms” above). But tell them to keep in mind that only 10%–15% of lung cancers occur in nonsmokers.

Treatment picture
If lung cancer is caught early and hasn’t spread far, the first step is surgery to remove the cancer along with some of the surrounding healthy tissue. According to Dr. Jennifer Temel, who treats lung cancer patients at Massachusetts General Hospital in Boston, “Surgery is the backbone of curing lung cancer. If people can’t have surgery, they’re generally incurable, with small exceptions.”

About half of the 170,000 new cases diagnosed each year are already incurable because the cancer has spread within the lung or to other organs. In addition, many older patients have poor lung function or other conditions that preclude surgery. Even in younger patients, symptoms may not appear until the disease is at a stage where surgery is unlikely to help.

Until recently, the only treatments for lung cancer were surgery or, if surgery wasn’t possible, radiation. (Radiation is also useful for controlling complications such as bone pain.) Chemotherapy is now given after surgery (and sometimes after radiation) because it’s been shown to reduce recurrence by around 10%.

It’s likely to be awhile before lung cancer treatment undergoes the kind of revolution that’s taken place in managing breast cancer. But there are stirrings of change in the way clinicians approach the disease. Targeted agents like Iressa and Tarceva, for example, may be used more often or earlier in women, especially nonsmokers, because they seem to respond better than men. “It used to be that everyone was treated the same,” says Dr. Lecia Sequist, a clinician at Massachusetts General Hospital and an expert in EGFR-related lung cancer. “Now, people are thinking, Is this a man or a woman? Is this a smoker or a nonsmoker? So that’s good.”

Another recent therapy is Avastin, which helps thwart the growth of blood vessels that nourish the cancer (a process called angiogenesis). Compared with chemotherapy alone, Avastin combined with standard chemotherapy has been shown to prolong survival in lung cancer patients by more than two months.

Moving forward

Early detection is crucial in preventing lung cancer death. The five-year survival rate for lung cancer patients as a group is only 15%, but it’s 50% in those who are treated before the cancer spreads outside the lungs.

Unfortunately, there is no equivalent of mammography or colonoscopy for the early detection of lung cancer. Chest x-rays don’t pick up tiny lung cancers. Although computed tomography (CT) is an improvement, using it as a screening test hasn’t been shown to reduce lung cancer mortality. However, most of the screening studies haven’t included women, so the issue is far from settled. In the U.S. the National Cancer Institute has embarked on a large screening trial, underway in 2005, that will compare spiral CT (which rotates around the patient to scan the chest) with standard chest x-rays in both women and men. Results aren’t expected until 2010.

It should go without saying that the best way for patients to prevent lung cancer is to avoid tobacco smoke. It’s the chief cause of lung cancer and cancer-related deaths. (It also causes cancers of the mouth and throat, kidneys, pancreas, cervix, and bladder, and contributes to cardiovascular disease and osteoporosis.) Secondhand smoke also counts: it causes an estimated 50,000 deaths each year in the United States alone.

This article is provided courtesy of Harvard Medical International.
© 2005 President and Fellows of Harvard College||**||

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