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Differences between a Primary Cancer and a Secondary Cancer


Many people become confused over the definitions of a primary vs secondary or second cancer. Primary cancer is defined as the original site (organ or tissue) where cancer began. In contrast, a second or secondary cancer may be defined in a few ways; as either a new primary cancer in another region of the body or as metastasis (spread) of the original primary cancer to another region of the body.

Diagram of cancer cells illustrating primary versus secondary cells
For example, cancer starting in the lungs is called primary lung cancer. If lung cancer spreads to the brain, it would be called primary lung cancer metastatic to the brain, or secondary brain cancer. In this case, the cancer cells in the brain would be lung cancer cells, not cancerous brain cells. Conversely, a person may have primary lung cancer and second primary brain cancer that is unrelated. In this case, the cancerous cells in the brain would be brain cells and not lung cells.

Primary Cancer
As noted above, primary cancer refers to the initial cancer a person experiences, whether that is lung cancer, breast cancer, or another type of cancer. It’s possible to have more than one primary cancer; sometimes these primary cancers are found at the same time, and sometimes they occur decades apart (see below). This isn’t surprising, as some of the risk factors for cancer, such as smoking, raise the risk of several types of cancer. There are also a number of hereditary cancer syndromes that increase the risk of cancer in more than one organ or tissue type.

Second Primary vs Secondary Cancer
The terms second and secondary cancer are sometimes used interchangeably but can mean different things. The term secondary cancer may refer to either metastasis from primary cancer, or second cancer unrelated to the original cancer. When the term second cancer is used, it usually refers to a second primary cancer, in other words, a different cancer than the first cancer, arising in a different organ or tissue.

Second Primary Cancers
Second primary cancers are unrelated directly to primary cancer, in that each of these cancers arise from mutations that take place in different cells. That said, second primary cancers are more common in people who have had primary cancer than in people who have not had cancer for several reasons. These include:

Similar risk factors: Some risk factors for cancer increase the risk of several types of cancer.
For example, smoking is linked to several types of cancer. There are several cancers associated with excess alcohol consumption as well, and so on.

Hereditary predisposition: Some people inherit a predisposition to cancer that can raise the risk of developing several different types of cancer.1 For example, mutations in tumor suppressor genes such as BRCA2 gene mutations, raise the risk not only of breast cancer, but ovarian cancer, prostate cancer, leukemia, pancreatic cancer, and lung cancer in women who smoke.
Treatment related cancers: Treatments for cancer, such as many chemotherapy drugs and radiation therapy can increase the risk of developing another cancer down the line2 . For example, one of the chemotherapy drugs commonly used for breast cancer can increase the risk of developing leukemia. Second primary cancers as one of the potential long-term side effects of cancer treatment is an active area of research, with studies looking for radiation therapy options as well as chemotherapy drugs that are less likely to lead to a second primary cancer.
With people surviving longer with cancer, the incidence of second primary cancers is expected to rise and is already significant. A 2017 Israeli study found that among breast cancer survivors, 3.6 percent developed a second primary cancer within 5 years of their original diagnosis, and 8.2 percent within 10 years of their diagnosis.3 Another way of understanding the gravity of the problem is by looking at the impact of second primary cancers in people who have had cancer. At the current time, second primary cancers are the second leading cause of death (after the original cancer) in people with head and neck cancers.

With Hodgkin disease, the treatment of the disease which is often at a young age combined with a high survival rate is associated with a high risk of secondary cancers. It’s thought that the risk may be as high as 20 percent to 30 percent.4 For this reason, screening, such as MRI screening for breast cancer (instead of mammograms which can miss up to 15 percent of breast cancers) is often recommended.

Cancer of Unknown Origin
In some cases, the original site where a cancer starts is unknown, and doctors may be uncertain if a cancer that is diagnosed is secondary cancer (metastasis) from a cancer that hasn’t yet been found, or instead of a primary cancer. For 3 out of every hundred people with cancer, the primary site of cancer isn’t found. When this is the case, the tumor is usually referred to as a metastatic cancer of unknown primary origin.

With improved diagnostic tests and molecular profiling, a diagnosis of cancer of unknown origin is less common than in the past, but this does still occur. The reason is often because a tumor is very “undifferentiated.” Cancer cells may resemble normal cells, sometimes making them relatively indistinguishable under a microscope. Even if a primary site is unable to be determined for a cancer, doctors are still able to treat that cancer.

Cancers do not always have a primary site. An example of this is lymphoma. Yet while the primary site where a lymphoma begins may not be known, it is not considered to be a cancer of unknown origin. Tumors such as this can be confusing when talking about primary vs second cancers, as lymphomas may be found in many tissues. In this case, however, the cells would all be lymphoma cells under the microscope such that if cancer cells in the stomach were lymphoma cells, it would be part of the primary cancer, but if they were stomach cells, it would be considered a second primary cancer.

The terminology surrounding cancer, especially when a person develops more than one type of cancer or has metastatic disease, can be confusing. At the same time, we know it’s very important to be your own advocate in your care, and understanding your disease is essential in order to do this. Take time to learn about your cancer. Ask a lot of questions. If the answers are still unclear, ask again. And, don’t hesitate to request a second opinion before making any decisions. The distinction between primary and secondary cancer can make a significant difference in treatment options and approaches.

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