We all know that there are fundamental differences in anatomy between the sexes. As they say, vive la différence. But there are other physiological differences that sometimes show up in diseases and conditions, where you might not expect to see them. One such difference arises in women and lung cancer.
Lung cancer was long thought of as a “man’s disease,” and today, more men still die of the condition than women on average. But women have been catching up to men, and some of these sex-related differences in lung cancer can be attributed to smoking patterns and habits. The rate of smoking among women continued to rise into the 1960s among women well after it had stabilized for men, says Dr. Humberto K. Choi, a pulmonologist at the Cleveland Clinic in Ohio. That means the rate of incidence of lung cancer and its mortality rates continued to rise for women after it had leveled off for men. “For example, lung cancer mortality stabilized in the ’70s among men while it stabilized only in the ’90s for women,” Choi says.
[See: 7 Things You Didn’t Know About Lung Cancer.]
Although smoking is the leading risk factor for lung cancer — it’s responsible for 80 to 90 percent of all cases of lung cancer in both sexes, Choi says — lung cancer can and does occur in people who have no smoking history. But according to the U.S. Department of Health & Human Services’ Office on Women’s Health, that’s an area of inequity: “1 in 5 women diagnosed with lung cancer have never smoked.” That’s compared to 1 in 10 cases of lung cancer in male never-smokers.
Women, particularly younger nonsmoking women, do seem to be somewhat more likely to develop lung cancer than men, but why exactly is still mostly a mystery, despite intensive research into this area looking at everything from hormones and genetics to environmental exposures and lifestyle factors.
One reason is the level of exposure the average woman gets to carcinogens from the average cigarette, Choi says. Within a single brand of cigarette, each contains the same amount of toxins regardless of who’s smoking it. Men, on average, are larger than women, and thus have larger lungs. Therefore, the toxins from each cigarette a woman smokes may be more concentrated in some women’s lungs, which could lead to a higher chance of quicker development of lung cancer.
What’s more, “the proportion of lung cancer cases in non-smoking women is higher compared with non-smoking men. Approximately 20 percent of women with lung cancer never smoked,” roughly double the percentage of non-smoking men, Choi says. The OWH reports that women are more likely to develop non-small cell lung cancer, the most common form of lung cancer that accounts for about 85 percent of all cases. It’s more prevalent among non-smokers.
No one is exactly sure why non-smoking women seem more likely to develop lung cancer than male never-smokers, but “proposed explanations include differences in environmental exposures, genetic differences, hormonal differences and molecular abnormalities,” Choi says.
Dr. Bryan Stanifer, a thoracic surgeon and director of the Women’s Lung and Health Center at New York-Presbyterian/Columbia University Medical Center, is studying the reasons women seem to have a different risk profile for lung cancer than men. He says figuring that out is “my whole mission here at Columbia,” and the reason he started the Women’s Lung and Health Center.
“Just to put some numbers on some of this, when you talk about lung cancer, there’s small cell and non-small cell lung cancer. Eighty-five percent of lung cancer is non-small cell, which includes adenocarcinoma and squamous cell carcinoma. When you look at that group, the majority — 85 percent — of cases occur in smokers. Just under half of those [patients] are women, and then 15 percent [of cases] occur in nonsmokers. Two-thirds of those [nonsmoking cases] are women, and nobody knows why. If you’re talking about lung cancer overall in all comers it’s about 55 percent male, 45 percent female, and the median age at diagnosis is 70. But if you start looking at nonsmokers and the patients who are less than 60 years old, it’s a majority women.”
Why, however, is not clear. “There’s lots of theories, but it’s never been adequately studied, which is part of our mission here. The theories include everything from, is there a hormonal component? Is there some specific environmental exposure that women get that men that on average tend not to get as much? But the ultimate answer is that no one knows right now. We currently do not fully understand why more young, non-smoking women are getting lung cancer. More research is actively being undertaken to help these patients in the future.”
[See: What Not to Say to Someone With Lung Cancer.]
As Stanifer noted, hormones may play a role. Estrogen can be expressed in some forms of lung cancer. A 2017 review study in the International Journal of Molecular Sciences reported that while estrogen’s role in female sexual development, reproduction and breast cancer has long been understood, this hormone that is synthesized in the ovaries appears to have other effects in the body, too. But increasingly, researchers are investigating whether estrogen can also sometimes be implicated in the development of lung cancer. “Estrogen receptors are consistently found in lung cancer tissues and cell lines, especially adenocarcinoma,” which is a form of lung cancer that women are more likely to get, the study noted. Estrogen has also “been reported to adversely affect the prognosis of lung cancer patients, however, there are several studies with conflicting results about the effect of estrogen on the risk and/or survival of lung cancer.” In other words, there may well be a connection between estrogen and lung cancer, but determining exactly how and why that connection exists has yet to be clarified.
Treatment for lung cancer is essentially the same for both sexes, but varies from patient to patient depending on the individual’s overall health, stage and type of cancer and preferences. “The gender doesn’t necessarily dictate the treatment,” Choi says. “However, those patients who never smoked but developed lung cancer tend to have certain types of genetic mutations that help choose a specific therapy. This is especially true when someone is diagnosed at an advanced disease stage. For example, patients with advanced lung cancer with an abnormality called EML4-ALK can be treated with a medication called crizotinib,” which goes by the brand name Xalkori.
To reduce your chances of developing lung cancer, first and foremost, don’t take up smoking. And if you do smoke, please try to quit. “Because lung cancer is so tightly associated with smoking, and because women seem to be more susceptible to the toxic effects of smoking, the best piece of advice is to never smoke,” Choi says. “And when someone is already smoking, they should quit. Even those low levels of smoking that someone may think is healthy can be harmful.”
Stanifer agrees, saying “the first step to reducing lung cancer risk is to stop smoking. This is by the far the biggest controllable risk factor. Avoiding secondhand smoke will also help.”
Quitting is hard, but it can be done, and it’s the biggest change you can make to reduce your chances of developing lung cancer and improve your chances of survival if you have lung cancer. Smoking is one of the few factors you have direct control over to reduce your chances of developing lung cancer. A May 2018 study in the Journal of the National Cancer Institute found that within five years of quitting smoking, the risk of developing lung cancer had declined 39.1 percent for previously heavy smokers. The risk of developing lung cancer continued to decline with each additional year after quitting.
If you can’t or won’t stop smoking, “there is the suggestion in some studies that taking beta carotene supplements can elevate lung cancer risk and should therefore be avoided,” Stanifer says. So talk to your doctor about any supplements or medications you take to make sure you’re not inadvertently increasing your risk.
Stanifer says you should also try to reduce environmental factors that have been shown to increase cancer risk, too. “Exposure to both radon and asbestos should be avoided. Radon can concentrate indoors. There are do-it-yourself kits to check your radon levels in your home that you can consider getting to make sure you aren’t getting elevated exposures.”
You should also talk to your doctor about any hormone therapies you may be taking. Some studies have shown a correlation between hormone replacement therapies and worse outcomes from lung cancer. The connection isn’t clear, but it seems that in some cases, HRT might augment the effects of cigarette smoking, meaning a higher mortality for women who both smoke and use HRT.
[See: 10 Innovations in Cancer Therapy.]
If you are or were a smoker or otherwise have an elevated risk of lung cancer, consider annual screening. Screening for lung cancer is done with low-dose CT scanning. “One of the largest ever cancer prevention trials, the National Lung Screening Trial, showed both a lung cancer specific and overall mortality advantage to enrolling in a screening program for those who qualify,” Stanifer says. “Insurance coverage and the specific criteria vary, but generally, all smokers or former smokers between the ages of 55 and 80 should look to see if they are eligible,” he says.
Screening for lung cancer has pros and cons — be sure to discuss the risks and benefits thoroughly with your doctor before you begin a screening protocol. Despite its potential harms, screening is currently the best way to detect lung cancer early, before it becomes a harder-to-treat problem. The earlier a cancer is detected, the less likely you are to die from it. The American Lung Association reports that the overall five-year survival rate for lung cancer is 18.6 percent, but improves to 55 percent for cases diagnosed in an early, local stage.
In addition to these strategies, it’s important to eat right, exercise regularly, keep your weight in check and visit your doctor if you develop a cough that won’t go away or other respiratory issues that don’t improve or return. Obesity and a sedentary lifestyle have been linked to increased risk for a variety of cancers, so for your overall health, it’s important to keep moving and eat a balanced diet.
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