What Is Lung Adenocarcinoma?

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Lung adenocarcinoma is a form of non-small cell lung cancer (NSCLC), the most common type of lung cancer. NSCLCs account for 80% of lung malignancies and, of these, roughly 50% are adenocarcinomas. Today, adenocarcinoma is the most common form of lung cancer in women, Asians, and people under 45, and can even affect non-smokers who have never smoked one cigarette.

While the rate of adenocarcinoma has been decreasing in men and leveling off in women, the numbers continue to rise in young, non-smoking women—and researchers are not entirely sure why. It is largely believed that genetics, secondhand smoke, and exposure to radon in the home are all contributing factors. Unfortunately, research into the possible causes is lacking, likely partly due to the fact that lung cancer is largely considered a "smoker's disease."

lung adenocarcinoma symptoms
Illustration by JR Bee, Verywell

Symptoms of Lung Adenocarcinoma

Lung adenocarcinomas usually begin in tissues near the outer portion of the lungs and may be there for a long time before symptoms appear. When they finally appear, the signs are often less obvious than other forms of lung cancer, manifesting with a chronic cough and bloody sputum only in later, more advanced stages of the disease.

Because of this, some of the more generalized early symptoms (such as fatigue, subtle shortness of breath, or upper back and chest pain) may be missed or attributed to other causes. As a result, diagnoses are often delayed, particularly among young people and non-smokers who may have never considered cancer a possibility or a threat.

Causes

As with all cancers, the cause of lung adenocarcinoma remains largely unknown. Research strongly suggests that genetic, environmental, and lifestyle factors play a part in the onset, risk, and severity of the disease.

Genetics

As one of three subtypes of NSCLC, lung adenocarcinoma is believed to be associated with certain genetic mutations that may predispose a person to the disease.

These include a mutation of the epidermal growth factor receptor (EGFR) gene, which provides the body with instructions on how to make structural proteins and regulates the speed at which that occurs. There are at least 10 known mutations that can affect the gene and cause cells to replicate abnormally and out of control.

EGFR mutations more commonly associated with less aggressive low- to intermediate-grade adenocarcinomas.

Other mutations associated with lung adenocarcinoma include those affecting the Kirsten rat sarcoma (KRAS) gene. Like EGFR, KRAS also regulates cell growth, maturation, and death; mutations are seen in 20% to 40% of lung adenocarcinoma cases.

However, people whose tumors have KRAS mutations typically have a poor prognosis. Even if the cancer responds well to initial chemotherapy, the disease almost invariably returns.

Adenocarcinoma-associated mutations are sometimes passed from parent to child. A 2017 review in the journal Oncology Letters suggests that having a parent or sibling with lung cancer increases your risk of the disease by 50% compared to people with no family history.

Other mutations may occur spontaneously; scientists are uncertain why.

Health Concerns and Lifestyle

Genetics only plays a part in the risk of lung adenocarcinoma. Other factors contribute significantly, not least of which is tobacco smoking.

According to the longstanding Nurses' Health Study, people who have smoked for 30 to 40 years are more than twice as likely to develop lung adenocarcinoma than those who never smoked. The risk is further doubled if you smoked for more than 40 years.

Secondhand smoke exposure also increases your risk.

Other factors that put you at risk for lung adenocarcinoma include:

These and other non-smoking-related risk factors account for why 20% of lung cancers occur in people who have never smoked a cigarette in their life.

Diagnosis

Lung cancer is often first detected when abnormalities are seen on an X-ray, usually in the form of a poorly defined shadow. While distressing, the finding at least offers the opportunity for early diagnosis.

In as many as 25% of lung cancer cases, a chest X-ray will not detect any irregularities and return a perfectly "normal" diagnosis.

If cancer is suspected, other, more sensitive diagnostics may be used, including:

If there any lingering concerns after a chest X-ray, such further studies should be ordered.

Sputum cytology, in which a sample of coughed up saliva and mucus is evaluated, may also be used, but this is considered less useful in diagnosing early cancer.

Depending on the results, your doctor may want to obtain a sample of lung tissue to confirm the diagnosis. In addition to more invasive lung tissue biopsies, a newer blood test called a liquid biopsy may be able to follow specific genetic abnormalities in lung cancer cells such as EGFR mutations.

Genetic Profiling

One of the more exciting advances in oncology has been the use of genetic testing to profile cancer cells. By doing so, doctors can select treatments able to target those specific genetic variations.

Current guidelines recommend that all persons with advanced lung adenocarcinoma have PD-L1 immunohistochemistry (PH-L1 IHC) conducted. This genetic test profiles one's cancer and helps predict the potential effectiveness of one of four immunotherapy drugs approved for the treatment of the disease.

That said, PD-L1 testing is far from perfect in predicting who will or will not respond to these drugs. Other tests, such as tumor mutation burden (the number of mutations present in a tumor) may help identify who will most benefit from these newer targeted therapies.

Reviewing your molecular and PD-L1 tests is one of the most important steps when first diagnosed with advanced lung adenocarcinoma. Specific treatments are available not only for those with EGFR mutations but other treatable mutations such as BRAF, ERBB2, ALK rearrangements, ROS1 rearrangements, and others.

Cancer Staging

Once a cancer diagnosis is confirmed, the doctor will stage the disease based on a series of standard tests. The aim of staging is to determine how advanced the lung cancer is and to what extent it has spread (metastasized).

Staging helps direct treatment in a more appropriate manner so that a malignancy is neither undertreated (affecting outcomes) nor overtreated (causing unnecessary side effects).

If a case is considered occult lung cancer, it means that cancer cells are found in sputum but a lung tumor cannot be found by imaging studies. Stage 0 means the cancer is limited to the lining of the airways and is not yet invasive.

Beyond that, there are four stages that are defined as follows. These terms will be used when discussing treatment options.

Classification Corresponding Stage(s) Treatment Options
Early-stage lung cancer Stage 1: Localized and not spread to any lymph nodes

Stage 2: Spread to lymph nodes, the lining of the lungs, or their major passageways
Potentially curable with surgery
Locally advanced lung cancer Stage 3A: Spread to lymph nodes on the same side of the body as the tumor, but not distant regions Surgery possible; adjuvant treatment with chemotherapy and radiation therapy usually required
Advanced lung cancer Stage 3B: Spread to distant lymph nodes or invasion of other structures in the chest

Stage 4: Spread to the other lung, another region of the body, or the fluid around the lung or heart

Non-surgical treatments are best. All but a few rare cases are considered inoperable.



Treatment

Depending on the stage of the disease, treatment may include one therapy or a combination.

  • Surgery may be offered in the early stages, either alone or accompanied by chemotherapy and/or radiation therapy. When successful, surgery offers the best chance of curing lung cancer.
  • Chemotherapy may be used alone, in conjunction with radiation therapy, or before or after surgery.
  • Targeted therapies attack specific genetic mutations by recognizing specific proteins on cancer cells and blocking their ability to replicate. Options include Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), Xalkori (crizotinib), Zykadia (ceritinib), Alecnensa (alectinib), and Tagrisso (osimertinib). More are undergoing clinical investigation.
  • Radiation therapy may be used either to treat cancer or control symptoms in those with metastatic cancer. More targeted forms of radiation (stereotactic body radiotherapy (SBRT), proton therapy) may be used for smaller cancers that surgery cannot reach. SBRT is now also being used to treat brain metastases and other metastases in people with lung cancer if only a few are present.
  • Immunotherapy aims to harness the body's immune system to fight cancer. Current options include Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab) and Imfinzi (durvalumab) for stage 3 and 4 lung cancer.

Targeted therapies are far less generalized than earlier generation treatments that attacked both healthy and unhealthy cells, resulting in severe and even intolerable side effects. Clinical trials are in the process of identifying more common mutations that can be targeted with medication. This area of treatment is still in its infancy and rapidly evolving.

Clinical trials of targeted and other therapies provide hope to those in whom approved treatments have either failed or cause severe side effects. The NCI recommends that people with lung cancer consider taking part in a clinical trial.

In the past, the likelihood that a clinical trial would make a difference for a person with cancer was small, but this is changing rapidly as specific targets in the pathway of cancer cell division are identified. Many people with stage 4 lung cancer are only alive because of their participation in a clinical trial.

Finally, many physicians recommend getting a second opinion from another specialist or one of the National Cancer Institute (NCI)-designated treatment centers actively involved in lung cancer research. Doing so can help ensure you get the most up-to-date treatment information and are better able to make an informed choice.

A Word From Verywell

Because the early symptoms of lung cancer are often difficult to spot, the average five-year survival rate is only around 18%. For those diagnosed in the early stages, the outlook is far more promising.

What this highlights is the need for greater awareness about the nonspecific or atypical symptoms of lung cancer. On their own, the symptoms may be easy to miss. Together, they may raise a red flag that can lead to early diagnosis and earlier, more effective treatment.

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