Lung cancer

What is lung cancer?

Lung cancer is a type of cancer that begins in the lungs. Lung cancer begins in the lungs and may spread to lymph nodes or other organs in the body, such as the brain. Cancer from other organs also may spread to the lungs. When cancer cells spread from one organ to another, they are called metastases.

All cells in the body contain the genetic material called deoxyribonucleic acid (DNA). Every time a mature cell divides into two new cells, its DNA is exactly duplicated. The cells are copies of the original cell, identical in every way. In this way, our bodies continually replenish themselves. Old cells die off and the next generation replaces them.

A cancer begins with an error, or mutation, in a cell’s DNA. DNA mutations can be caused by the normal aging process or through environmental factors, such as cigarette smoke, breathing in asbestos fibers, and to exposure to radon gas.

Researchers have found that it takes a series of mutations to create a lung cancer cell. Before becoming fully cancerous, cells can be precancerous, in that they have some mutations but still function normally as lung cells. When a cell with a genetic mutation divides, it passes along its abnormal genes to the two new cells, which then divide into four cells with errors in their DNA and so on. With each new mutation, the lung tissue cell becomes more mutated and may not be as effective in carrying out its function as a lung cell. At a later stage of disease, some cells may travel away from the original tumor and start growing in other parts of the body. This process is called metastasis and the new distant sites are referred to as metastases.

Primary Versus Secondary Lung Cancer

Primary lung cancer starts in the lungs. The cancer cells are abnormal lung cells. Sometimes, people will have cancer travel from another part of their body or metastasize to their lungs. This is called secondary lung cancer because the lungs are a secondary site compared to the original primary location of the cancer. So, for example, breast cancer cells which have traveled to the lung are not lung cancer but rather metastatic breast cancer and will require treatment prescribed for breast cancer rather than lung cancer.

Risk factors for lung cancer

A risk factor is anything that increases a person’s chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But having a risk factor, or even several, does not mean that you will get the disease. And some people who get the disease may have few or no known risk factors.

Several risk factors can make you more likely to develop lung cancer.  These factors are related to the risk of lung cancer in general. It’s possible that some of these might not apply to small cell lung cancer (SCLC).

Risk factors you can change

Tobacco smoke

Smoking is by far the leading risk factor for lung cancer. About 80% of lung cancer deaths are thought to result from smoking and this number is probably even higher for small cell lung cancer (SCLC). It’s very rare for someone who has never smoked to have SCLC.

The risk of lung cancer for smokers is many times higher than for non-smokers. The longer you smoke and the more packs a day you smoke, the greater your risk.

Cigar smoking and pipe smoking are almost as likely to cause lung cancer as cigarette smoking. Smoking low-tar or “light” cigarettes increases lung cancer risk as much as regular cigarettes. Smoking menthol cigarettes might increase the risk even more since the menthol may allow smokers to inhale more deeply.

Secondhand smoke

If you don’t smoke, breathing in the smoke of others (called secondhand smoke or environmental tobacco smoke) can increase your risk of developing lung cancer. Secondhand smoke is thought to cause more than 7,000 deaths from lung cancer each year.

Exposure to radon

Radon is a naturally occurring radioactive gas that results from the breakdown of uranium in soil and rocks. You can’t see, taste, or smell it. According to the US Environmental Protection Agency (EPA), radon is the second leading cause of lung cancer in this country, and is the leading cause among non-smokers.

Outdoors, there is so little radon that it is not likely to be dangerous. But indoors, radon can be more concentrated. Breathing it in exposes your lungs to small amounts of radiation. This may increase a person’s risk of lung cancer.

Homes and other buildings in nearly any part of the United States can have high indoor radon levels (especially in basements).

Exposure to asbestos

People who work with asbestos (such as in mines, mills, textile plants, places where insulation is used, and shipyards) are several times more likely to die of lung cancer. Lung cancer risk is much greater in workers exposed to asbestos who also smoke. It’s not clear how much low-level or short-term exposure to asbestos might raise lung cancer risk.

People exposed to large amounts of asbestos also have a greater risk of developing mesothelioma, a type of cancer that starts in the pleura (the lining surrounding the lungs). For more on this type of cancer, see Malignant Mesothelioma.

In recent years, government regulations have greatly reduced the use of asbestos in commercial and industrial products. It’s still present in many homes and other older buildings, but it’s not usually considered harmful as long as it’s not released into the air by deterioration, demolition, or renovation. For more information, see Asbestos and Cancer Risk.

Exposure to other cancer-causing agents in the workplace

Other carcinogens (cancer-causing agents) found in some workplaces that can increase lung cancer risk include:

• Radioactive ores such as uranium
• Inhaled chemicals such as arsenic, beryllium, cadmium, silica, vinyl chloride, nickel compounds, chromium compounds, coal products, mustard gas, and chloromethyl ethers
• Diesel exhaust

The government and industry have taken steps in recent years to help protect workers from many of these exposures. But the dangers are still there, so if you work around these agents, be careful to limit your exposure whenever possible.

Taking certain dietary supplements

Studies looking at the possible role of vitamin supplements in reducing lung cancer risk have had disappointing results. In fact, 2 large studies found that smokers who took beta carotene supplements actually had an increased risk of lung cancer. The results of these studies suggest that smokers should avoid taking beta carotene supplements.

Arsenic in drinking water

Studies of people in parts of Southeast Asia and South America with high levels of arsenic in their drinking water have found a higher risk of lung cancer. In most of these studies, the levels of arsenic in the water were many times higher than those typically seen in the United States, even areas where arsenic levels are above normal. For most Americans who are on public water systems, drinking water is not a major source of arsenic.

Risk factors you cannot change

Previous radiation therapy to the lungs

People who have had radiation therapy to the chest for other cancers are at higher risk for lung cancer, particularly if they smoke. Examples include people who have been treated for Hodgkin disease or women who get chest radiation after a mastectomy for breast cancer. Women who have radiation therapy to the breast after a lumpectomy do not appear to have a higher than expected risk of lung cancer.

Air pollution

In cities, air pollution (especially near heavily trafficked roads) appears to raise the risk of lung cancer slightly. This risk is far less than the risk caused by smoking, but some researchers estimate that worldwide about 5% of all deaths from lung cancer may be due to outdoor air pollution.

Personal or family history of lung cancer

If you have had lung cancer, you have a higher risk of developing another lung cancer.

Brothers, sisters, and children of people who have had lung cancer may have a slightly higher risk of lung cancer themselves, especially if the relative was diagnosed at a younger age. It’s not clear how much of this risk might be due to shared genes among family members and how much might be from shared household exposures (such as tobacco smoke or radon).

Researchers have found that genetics seems to play a role in some families with a strong history of lung cancer.

Factors with uncertain or unproven effects on lung cancer risk

Smoking marijuana

There are reasons to think smoking marijuana might increase lung cancer risk.

• Marijuana smoke contains tar and many of same cancer-causing substances that are in tobacco smoke. (Tar is the sticky, solid material that remains after burning, which is thought to contain most of the harmful substances in smoke.)
• Marijuana cigarettes (joints) are typically smoked all the way to the end, where tar content is the highest.
• Marijuana is inhaled very deeply and the smoke is held in the lungs for a long time, which gives any cancer-causing substances more opportunity to deposit in the lungs.
• Because marijuana is still illegal in many places, it may not be possible to control what other substances it might contain.

Those who use marijuana tend to smoke fewer marijuana cigarettes in a day or week than the amount of tobacco consumed by cigarette smokers. The lesser amount smoked would make it harder to see an impact on lung cancer risk.

It’s been hard to study whether there is a link between marijuana and lung cancer because marijuana has been illegal in many places for so long, and it’s not easy to gather information about the use of illegal drugs. Also, in studies that have looked at past marijuana use in people who had lung cancer, most of the marijuana smokers also smoked cigarettes. This can make it hard to know how much any increased risk is from tobacco and how much might be from marijuana. More research is needed to know the cancer risks from smoking marijuana.

E-cigarettes

E-cigarettes are a type of electronic nicotine delivery system. They do not contain any tobacco but the Food and Drug Administration (FDA) classifies them as “tobacco” products. E-cigarettes are fairly new and more research is needed to know what the long-term effects might be, including the risk of developing lung cancer.

Talc and talcum powder

Talc is a mineral that in its natural form may contain asbestos. Some studies have suggested that talc miners and people who operate talc mills might have a higher risk of lung cancer and other respiratory diseases because of their exposure to industrial grade talc. But other studies have not found an increase in lung cancer rate.

Talcum powder is made from talc. The use of cosmetic talcum powder has not been found to increase lung cancer risk.

Types of lung cancer

There are 2 main types of lung cancer and they are treated very differently.

Non-small cell lung cancer (NSCLC)

About 80% to 85% of lung cancers are NSCLC. The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. These subtypes, which start from different types of lung cells are grouped together as NSCLC because their treatment and prognoses (outlook) are often similar.

Adenocarcinoma: Adenocarcinomas start in the cells that would normally secrete substances such as mucus.

This type of lung cancer occurs mainly in current or former smokers, but it is also the most common type of lung cancer seen in non-smokers. It is more common in women than in men, and it is more likely to occur in younger people than other types of lung cancer.

Adenocarcinoma is usually found in the outer parts of the lung and is more likely to be found before it has spread.

People with a type of adenocarcinoma called adenocarcinoma in situ (previously called bronchioloalveolar carcinoma) tend to have a better outlook than those with other types of lung cancer.

Squamous cell carcinoma: Squamous cell carcinomas start in squamous cells, which are flat cells that line the inside of the airways in the lungs. They are often linked to a history of smoking and tend to be found in the central part of the lungs, near a main airway (bronchus).

Large cell (undifferentiated) carcinoma:  Large cell carcinoma can appear in any part of the lung. It tends to grow and spread quickly, which can make it harder to treat. A subtype of large cell carcinoma, known as large cell neuroendocrine carcinoma, is a fast-growing cancer that is very similar to small cell lung cancer.

Other subtypes: A few other subtypes of NSCLC, such as adenosquamous carcinoma and sarcomatoid carcinoma, are much less common.

Small cell lung cancer (SCLC)

About 10% to 15% of all lung cancers are SCLC and it is sometimes called oat cell cancer.

This type of lung cancer tends to grow and spread faster than NSCLC. About 70% of people with SCLC will have cancer that has already spread at the time they are diagnosed. Since this cancer grows quickly, it tends to respond well to chemotherapy and radiation therapy. Unfortunately, for most people, the cancer will return at some point.

Other types of lung tumors

Along with the main types of lung cancer, other tumors can occur in the lungs.

Lung carcinoid tumors: Carcinoid tumors of the lung account for fewer than 5% of lung tumors. Most of these grow slowly. For more information about these tumors, see Lung Carcinoid Tumor.

Other lung tumors: Other types of lung cancer such as adenoid cystic carcinomas, lymphomas, and sarcomas, as well as benign lung tumors such as hamartomas are rare. These are treated differently from the more common lung cancers and are not discussed here.

Cancers that spread to the lungs: Cancers that start in other organs (such as the breast, pancreas, kidney, or skin) can sometimes spread (metastasize) to the lungs, but these are not lung cancers. For example, cancer that starts in the breast and spreads to the lungs is still breast cancer, not lung cancer. Treatment for metastatic cancer to the lungs is based on where it started (the primary cancer site).

Symptoms of lung cancer

Lung cancer typically doesn’t cause signs and symptoms in its earliest stages. Signs and symptoms of lung cancer typically occur only when the disease is advanced.

Signs and symptoms of lung cancer may include:

• A new cough that doesn’t go away
• Coughing up blood, even a small amount
• Shortness of breath
• Chest pain
• Hoarseness
• Losing weight without trying
• Bone pain
• Headache

If the original lung cancer has spread, a person may feel symptoms in other places in the body. Common places for lung cancer to spread include other parts of the lungs, lymph nodes, bones, brain, liver, and adrenal glands.

Symptoms of lung cancer that may occur elsewhere in the body:

• Loss of appetite or unexplained weight loss
• Muscle wasting (also known as cachexia)
• Fatigue
• Headaches, bone or joint pain
• Bone fractures not related to accidental injury
• Neurological symptoms, such as unsteady gait or memory loss
• Neck or facial swelling
• General weakness
• Bleeding
• Blood clots

Lung cancer diagnosis

If lung cancer is suspected as a result of a screening procedure (CT, MRI or PET scan), a small piece of tissue from the lung must be examined under a microscope to look for cancer cells. Called a biopsy, this procedure can be performed in different ways. In some cases, the doctor passes a needle through the skin into the lungs to remove a small piece of tissue; this procedure is often called a needle biopsy.

In other cases, a biopsy may be done during a bronchoscopy. With the patient under sedation, the doctor inserts a small tube through the mouth or nose and into the lungs. The tube, which has a light, small camera and a surgical instrument on the end, allows the doctor to see inside the lung and remove a small tissue sample.

Recently, the FDA approved the first liquid biopsy for lung cancer which utilizes free floating DNA in the bloodstream for analysis. Tumors shed this DNA material into the blood as the cells within them die. The DNA is collected and analyzed allowing doctors to get a “snapshot” of the genetic mutations and other irregularities that drive a tumor’s growth. Liquid biopsies offer some important advantages, in that they are non-invasive, inexpensive, provide timely results and are easily repeatable.

If cancer cells are found in the tissue sample, a genetic test may be performed. Genetic testing, which may also be referred to as “molecular profiling or mutation profiling,” allows doctors to look inside tumor cells for gene mutations or changes that may have caused them to be cancerous. This testing helps a doctor develop a treatment plan for the patient.

Pathologists (doctors who identify diseases by studying cells and tissues under a microscope) and geneticists (scientists with special training in the study of genes) can give your doctor the information he or she needs to tailor a treatment that will be most effective. These specialists can determine the distinct characteristics of each lung cancer: the tumor type (NSCLC or SCLC, for example); how far it has advanced (its stage); and the mutations (gene changes) that cause or “drive” the cancer.

As the importance of understanding the genetic characteristics of a lung tumor cell has increased, pathologists and pulmonologists are encouraging that reflex testing be carried out. Reflex testing involves performing testing for currently known lung cancer mutations or drivers at the same time that the diagnostic testing is carried out, irrespective of the patient’s tumor staging.

Stages of lung cancer

Stage I: The cancer is located only in the lungs and has not spread to any lymph nodes.

Stage II: The cancer is in the lung and nearby lymph nodes.

Stage III: Cancer is found in the lung and in the lymph nodes in the middle of the chest, also described as locally advanced disease. Stage III has two subtypes:

• If the cancer has spread only to lymph nodes on the same side of the chest where the cancer started, it is called stage IIIA.
• If the cancer has spread to the lymph nodes on the opposite side of the chest, or above the collar bone, it is called stage IIIB.

Stage IV: This is the most advanced stage of lung cancer, and is also described as advanced disease. This is when the cancer has spread to both lungs, to fluid in the area around the lungs, or to another part of the body, such as the liver or other organs.

Treatment of lung cancer

Surgery, radiation, chemotherapy, targeted treatments and immunotherapy —alone or in combination—are used to treat lung cancer. Each of these types of treatments may cause different side effects.

Surgery

Most stage I and stage II non-small cell lung cancers are treated with surgery to remove the tumor. For this procedure, a surgeon removes the lobe, or section, of the lung containing the tumor.

Some surgeons use video-assisted thoracoscopic surgery (VATS). For this procedure, the surgeon makes a small incision, or cut, in the chest and inserts a tube called a thoracoscope. The thoracoscope has a light and a tiny camera connected to a video monitor so that the surgeon can see inside the chest. A lung lobe can then be removed through the scope, without making a large incision in the chest.

Chemotherapy and Radiation

For people with non-small cell lung tumors that can be surgically removed, evidence suggests that chemotherapy after surgery, known as “adjuvant chemotherapy,” may help prevent the cancer from returning. This is particularly true for patients with stage II and IIIA disease. Questions remain about whether adjuvant chemotherapy applies to other patients and how much they benefit.

For people with stage III lung cancer that cannot be removed surgically, doctors typically recommend chemotherapy in combination with definitive (high-dose) radiation treatments. In stage IV lung cancer, chemotherapy is typically the main treatment. In stage IV patients, radiation is used only for palliation of symptoms.

The chemotherapy treatment plan for lung cancer often consists of a combination of drugs. Among the drugs most commonly used are cisplatin (Platinol) or carboplatin (Paraplatin) plus docetaxel (Taxotere), gemcitabine (Gemzar), paclitaxel (Taxol and others), vinorelbine (Navelbine and others), or pemetrexed (Alimta).

There are times when these treatments may not work. Or, after these drugs work for a while, the lung cancer may come back. In such cases, doctors often prescribe a second course of drug treatment referred to as second-line chemotherapy.

Recently, the concept of maintenance chemotherapy has been tested in clinical trials, either as a switch to another drug before the cancer progresses; or to continue one of the drugs used initially for a longer period of time. Both of these strategies have shown advantages in selected patients.

Chemotherapy Before Other Treatments (Neoadjuvant Treatment)

Receiving chemotherapy before radiation or surgery may help people with lung cancer by shrinking the tumor enough to make it easier to remove with surgery, increasing the effectiveness of radiation and destroying hidden cancer cells at the earliest possible time.

If a tumor doesn’t shrink with chemotherapy, the medication can be stopped right away, allowing the doctor to try a different treatment. In addition, research shows that people with lung cancer are much more able to cope with the side effects of chemotherapy when it is given before surgery.

Sometimes, a short trial period of treatment with the drug shrinks the tumor before surgery. If that is the case, then continued treatment with the same drug after surgery is more likely to benefit the patient. Because many lung cancer specialists around the world are giving chemotherapy to their patients before surgery, patients should discuss it with their doctor.

Targeted Treatments

One of the most exciting developments in lung cancer medicine is the introduction of targeted treatments. Unlike chemotherapy drugs, which cannot tell the difference between normal cells and cancer cells, targeted therapies are designed specifically to attack cancer cells by attaching to or blocking targets that appear on the surfaces of those cells. People who have advanced lung cancer with certain molecular biomarkers may receive treatment with a targeted drug alone or in combination with chemotherapy. These treatments for lung cancer include:

Erlotinib (Tarceva and others). A targeted treatment called erlotinib has been shown to benefit some people with non-small cell lung cancer. This drug blocks a specific kind of receptor on the cell surface—the epidermal growth factor receptor (EGFR). Receptors such as EGFR act as doorways by allowing substances in that they can encourage a cancer cell to grow and spread. Lung cancer cells that have a mutation on the EGFR are likely to respond to treatment with erlotinib instead of chemotherapy. For patients who have received chemotherapy, and are in need of additional treatment, erlotinib can be used even without the presence of the mutation.

Afatinib (Gilotrif). In 2013, the FDA approved afatinib for the initial treatment of metastatic NSCLC in patients with the same EGRF gene mutations or deletions as those who can be treated successfully with erlotinib.

Gefitinib (Iressa). In 2015, the FDA approved gefitinib for the first-line treatment of patients with NSCLC whose tumors harbor specific types of EGFR gene mutations, as detected by an FDA-approved test.

Bevacizumab (Avastin). Just like normal tissues, tumors need a blood supply to survive. Blood vessels grow in several ways. One way is through the presence of a substance called vascular endothelial growth factor (VEGF). This substance stimulates blood vessels to penetrate tumors and supply oxygen, minerals, and other nutrients to feed the tumor. When tumors spread throughout the body, they release VEGF to create new blood vessels.

Bevacizumab works by stopping VEGF from stimulating the growth of new blood vessels. (Because normal tissues have an established blood supply, they are not affected by the drug.) When combined with chemotherapy, bevacizumab has been shown to improve survival in people with certain types of non-small lung cancer, such as adenocarcinoma and large cell carcinoma.

Crizotinib (Xalkori). A treatment that has shown benefits for people with advanced non–small cell lung cancer who have the ALK gene mutation. Crizotinib works by blocking ALK and stopping the growth of the tumor.

Ceritinib (Zykadia). This was approved in 2014 for people with metastatic ALK-positive lung cancer who cannot tolerate crizotinib or whose cancer continued to grow while being treated with crizotinib.

Because the genes of cancer cells can evolve, some tumors may become resistant to a targeted treatment. Medications to meet those challenges are being studied now in clinical trials, which often offer important treatment options for people with lung cancer.

Immunotherapy

Immunotherapy has recently emerged as a new treatment option for certain lung cancers. While any cancer treatment can cause side effects, immunotherapy is generally well-tolerated; this is in part due to its mechanism of action.

Our immune system is constantly working to keep us healthy. It recognizes and fights against danger, such as infections, viruses, and growing cancer cells. In general terms, immunotherapy uses our own immune system as a treatment against cancer.

In March 2015, the FDA approved the immunotherapy nivolumab (Opdivo) for the treatment of metastatic squamous NSCLC which was unsuccessfully treated with chemotherapy. Nivolumab works by interfering with a molecular “brake” known as PD-1 that prevents the body’s immune system from attacking tumors.

In 2016, the FDA approved a new immunotherapy called pembrolizumab (Keytruda) for the treatment of advanced NSCLC as an initial therapy. Its therapeutic activity is similar to that of nivolumab. Patients are tested for a protein known as PDL-1 and if a sufficient quantity is identified, they may qualify for this treatment.

Additional approaches to immunotherapy for lung cancer have shown promise in early clinical trials and are now in late-phase development. Treatments for NSCLC have advanced the furthest; however, a number of new immune-based treatments for SCLC are also in clinical development. These treatments fall into four main categories:

• Monoclonal antibodies are lab-generated molecules that target specific tumor antigens (a substance that the immune system sees as being foreign or dangerous).
• Checkpoint inhibitors target molecules that serve as checks and balances in the regulation of immune responses.
• Therapeutic vaccines target shared or tumor-specific antigens.
• Adoptive T-cell transfer is an approach in which T-cells (a type of white blood cell) are removed from the patient, genetically modified or treated with chemicals to enhance their activity, and re-introduced into the patient with the goal of improving the immune system’s anticancer response.

CAR T-Cell therapy and Natural Killer (NK) Cell therapies are some of the newer therapies for treatment of lung cancer.

How can lung cancer be prevented?

There’s no sure way to prevent lung cancer, but you can reduce your risk if you:

• Don’t smoke. If you’ve never smoked, don’t start. Talk to your children about not smoking so that they can understand how to avoid this major risk factor for lung cancer. Begin conversations about the dangers of smoking with your children early so that they know how to react to peer pressure.
• Stop smoking. Stop smoking now. Quitting reduces your risk of lung cancer, even if you’ve smoked for years. Talk to your doctor about strategies and stop-smoking aids that can help you quit. Options include nicotine replacement products, medications, and support groups.
• Avoid second-hand smoke. If you live with or work with a smoker, urge him or her to quit. At the very least, ask him or her to smoke outside. Avoid areas where people smoke, such as bars and restaurants, and seek out smoke-free options.
• Test your home for radon. Have the radon levels in your home checked, especially if you live in an area where radon is known to be a problem. High radon levels can be remedied to make your home safer. For information on radon testing, contact your local department of public health or a local chapter of the American Lung Association.
• Avoid carcinogens at work. Take precautions to protect yourself from exposure to toxic chemicals at work. Follow your employer’s precautions. For instance, if you’re given a face mask for protection, always wear it. Ask your doctor what more you can do to protect yourself at work. Your risk of lung damage from workplace carcinogens increases if you smoke.
• Eat a diet full of fruits and vegetables. Choose a healthy diet with a variety of fruits and vegetables. Food sources of vitamins and nutrients are best. Avoid taking large doses of vitamins in pill form, as they may be harmful. For instance, researchers hoping to reduce the risk of lung cancer in heavy smokers gave them beta carotene supplements. Results showed the supplements actually increased the risk of cancer in smokers.
• Exercise most days of the week. If you don’t exercise regularly, start out slowly. Try to exercise most days of the week.